David Agus: inbred retard?

Discussing a recent study (Directional dominance on stature and cognition in diverse human populations) that found an effect for runs of homozygosity on height and IQ within populations, Greg Cochran notes:

Some retards (British papers) have been spinning this as saying that there are big benefits to mixed-race marriage. Untrue: to avoid lots of ROH (runs of homozygosity), just marry someone who isn’t from the same isolated population as you. We’re talking outside the valley or across the river : intercontinental travel is not necessary. Now there might be a degree of hybrid vigor in some distant crosses (currently unclear) – but likely not enough to compensate for someone coming from a group that has low trait values. Marry a Pygmy and your kids are going to be short. Marry someone from a population whose average IQ is below 90 (much of the world) and your kids will on average be less smart.

CBS medical contributor David Agus (who, wikipedia informs us, "graduated cum laude in molecular biology from Princeton University and received his medical degree from the University of Pennsylvania School of Medicine in 1991") promotes this misinterpretation of the study in a segment on CBS This Morning:

Do kids from mixed genetic backgrounds have an advantage?

Additionally, although one would hope someone who majored in molecular biology at Princeton and co-founded a personal genomics company would know that any benefits from outcrossing will fully accrue in the first generation, Agus gleefully urges the viewer to imagine how much "taller and smarter" children will be if "people of different backgrounds" continue interbreeding generation after generation.

It's a pretty interesting study that tells us a lot because this is really the first couple generations where people of different backgrounds are having children and if this happens in one, one generation children are 1.2 cm shorter, think of if this continues to happen, so, taller and smarter.

Curiously, Agus, the grandson of a rabbi, married a pre-Connie Chung daughter of Maury Povich. That is, Agus chose to mate with a member of the same rather inbred narrow ethnic group as himself. But I'm sure now that he's aware of this study (confused though he may be about it) and excited about the eugenic prospects of racial mixing, he's urged his own children to marry Africans, with that same gleeful look in his eyes.

It’s Sunday night, and Agus is at Jerusalem’s Mamilla Hotel. He just arrived for the Global Forum, a gathering of 70 of the world’s thinkers hosted by Israel’s National Library, to discuss how the People of the Book can use their ancient lore for contemporary needs.

It was Shimon Peres, the honorary chairman of the event, who convinced Agus to attend. Agus and Peres are friends – though he’s not the nonagenarian’s doctor – and the two meet every six months or so. This time, Agus will be discussing Maimonides at the National Library, from the perspective of what he, Agus, believes.

But first he had to go back and read some of the good doctor’s words. It’s been a long time since Agus studied Maimonides at Philadelphia’s Akiba Hebrew Academy. What he found resonated. [. . .]

Now Agus combines teaching, research and patient work, along with spending a lot of time at places like the World Economic Forum, the Aspen Ideas Festival and TEDMED – TED for the health field. He’s also at the CBS studio at 4 a.m., several mornings per week.

“You get a passion to change things, and I decided I don’t care if I’m uncomfortable on camera,” said Agus, who calls himself an introvert by nature. “I need to be a role model and it’s awkward, but you have to do it, over and over again. I get to talk to four million people every morning on CBS. I can just talk, I can call a spade a spade. I look at my patients losing their lives on a daily basis, so I’ve got nothing to lose.”

[Steve Jobs’ ex-doctor is in, and he’s quoting Maimonides. http://www.timesofisrael.com/steve-jobs-ex-doctor-is-in-and-hes-quoting-maimonides/]

Criminality and intelligence in Finland

James Thompson summarizes a recent paper ("Intelligence and criminal behavior in a total birth cohort: An examination of functional form, dimensions of intelligence, and the nature of offending"):

They found that lower levels of intelligence are associated with greater levels of offending, that the IQ-offending association is mostly linear, with some curvilinear aspects at highest and lowest levels, and that the pattern is consistent across multiple measures of intelligence and offending. In some ways this is exactly as predicted and already observed, since the available literature shows that individuals with lower IQ are more likely to engage in criminal behaviour. Criminal offending was measured with nine different indicators from official records and intelligence was measured using three subscales (verbal, mathematical, and spatial reasoning) as well as a composite measure. The results show consistent evidence of mostly linear patterns, with some indication of curvilinear associations at the very lowest and the very highest ranges of intellectual ability. [. . .]

Note that violent crime is an order of magnitude higher in the bottom 20% of the population by ability than the top 20% of population by ability. The pattern is generally a linear one. The subscales of intelligence show the same pattern, though perhaps the spatial scores show a slightly less pronounced differential effect.

So, why do dull minds carry out criminal acts? The main effect is driven by general intelligence, so that raises a number of possibilities, in that highly g-loaded factors such as deficits in executive functions, including inhibition, processing speed, and attention are potentially linked to criminal behaviour. People with higher levels of intelligence are more dependable ( Deary et al., 2008b) and conscientious ( Luciano, Wainwright, Wright, & Martin, 2006), suggesting that they are more likely to think about the moral consequences of their actions compared to individuals with lower levels of intelligence. People with lower intelligence have been found to act more impulsively ( de Wit et al., 2007 and Funder and Block, 1989). People with lower levels of impulse control and related constructs, such as low self-control, have also been found to be significantly more likely to engage in various forms of criminal and antisocial behavior ( Gottfredson and Hirschi, 1990,Moffitt et al., 2011 and Pratt and Cullen, 2000). While only preliminary, current research suggests that lower levels of intelligence reduces the ability to weigh the costs and benefits of individual action, resulting in a greater propensity to make impulsive decisions, which in some cases involve illegal behaviour.

Related:

• Can racial differences in circulating testosterone explain racial differences in crime?
• What explains racial differences in crime?
• More on race, crime, and intelligence

ESHG 2014: The degree of Intellectual Disability is significantly associated with an excess of Runs of Homozygosity (ROH)

Title: P08.40-M - The degree of Intellectual Disability is significantly associated with an excess of Runs of Homozygosity (ROH)
Keywords: Intellectual Disability; ROH
Authors: I. Gandin1,2, F. Faletra2, M. Carella3, V. Pecile2, G. Ferrero4, E. Belligni4, P. Palumbo3, O. Palumbo3, P. Bosco5, C. Romano5, C. Belcaro1, D. Vozzi2, A. P. d'Adamo1,2; 1University of Trieste, Trieste, Italy, 2IRCCS Burlo Garofolo, Trieste, Italy, 3IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy, 4AO citta' della salute e della scienza, Torino, Italy, 5IRCCS Oasi Maria SS, Troina(EN), Italy.

Abstract: Several recent studies focused on the effect of extended homozygosity on highly complex and polygenic traits where recessive inheritance may play an important role. Since excess of homozygosity might increase the risk for disorders like schizophrenia, Alzheimer disease and autism, we have set out a study to investigate the effect of ROHs on the degree of Intellectual Disability (ID). About 370 unrelated individuals with ID were collected and classified into mild/moderate ID (MM-ID) for IQ ranging from 35-40 to 70-75 and severe/profound ID (SP-ID) for IQ below 35-40. High-density SNP array data were processed with the aim of detecting and analyze ROHs. Since different array platform were used, homozygosity and ROHs mean length were compared in MM-ID vs SP-ID separately in each dataset. Results were then combined for a meta-analysis. Our data revealed an association between the amount of homozygosity and the degree of ID, according to the recent findings on autism (Gamsiz et al., 2013). Accounting for principal components to control population stratification, we tested for ROHs mean length and detected significantly (p < 0.005) longer stretches in SP-ID compared to MM-ID. Weaker association was detected in burden ROH analysis, showing an increase of the percentage of genome covered by ROHs for SP-ID cases. Extent of ROHs seems to contribute to the pathogenesis of ID, suggesting that autosomal recessive variants have a crucial role on the modulation of the severity of ID that still need to be investigated.

ESHG 2014: Polygenic risk for ADHD is associated with impaired educational achievement and lower IQ in the general population

Title: C11.1 - Polygenic risk for ADHD is associated with impaired educational achievement and lower IQ in the general population
Keywords: ADHD; Polygenic scores; Educational attainment
Authors: E. Stergiakouli1, J. Martin2, M. L. Hamshere2, A. Thapar2, D. M. Evans1, N. J. Timpson1, G. Davey Smith1; 1MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom, 2MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, United Kingdom.

Abstract: Introduction
High levels of ADHD symptoms during childhood carry risk of worse academic performance and can impact on employment and earnings in adulthood. Polygenic score analysis was used to show that common risk alleles for clinical ADHD contribute to the risk of having higher ADHD symptoms in the general population (Martin et al. in press). We have used polygenic score analysis to investigate the contribution of common risk variants for clinical ADHD on educational performance and IQ in the general population.

Methods
Academic performance was assessed using results from Key Stage 3 national tests and externally marked GCSE examinations in 6,385 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Polygenic risk scores were calculated for ALSPAC children and their mothers based on the results of an ADHD GWAS (Stergiakouli et al. 2012).

Results
ADHD polygenic scores on the children were associated with worst educational outcomes as represented by both time points and also with lower IQ scores at age 15.5 (see Table). Moreover, ADHD polygenic scores on the mothers were associated with lower IQ in the mothers and worst educational outcomes in the children (see Table).

Discussion
Our results suggest that the same genetic variants that are relevant for an ADHD diagnosis are also implicated in impaired academic performance in the general population and lower IQ score in both children and adults.

ESEB 2013 abstracts and videos

Some abstracts and videos from the 2013 Congress of the European Society for Evolutionary Biology.

Genetic genealogy comes of age: advances in the use of deep-rooted pedigrees in human evolutionary research (video)

Author(s): Larmuseau, MHD, Van Geystelen, A, Decorte, R

Summary:

Research on the recent human evolution will benefit from the implementation of extended genetic genealogical data. The approach to combine deep-rooted pedigrees with genetic information advances the understanding of changes in the human population genetic structure during the last centuries. This recent advance is mainly based on the extensive growth of whole genome sequencing data and available genealogical data of high quality. Moreover, according to the latest genetic genealogical research the historical non-paternity rate in Western Europe is estimated around 1% per generation within the last four centuries, which means that the expected relationship between the legal genealogy and the genetics of DNA donors exists. Therefore, genetic genealogical data will help with three research aims of human evolutionary studies: (I) detecting signals of (past) population stratification and interpreting the population structure in a more objective manner, (II) obtaining the time scale and impact of particular detected gene flow events more accurately and (III) determining temporal genetic differentiation within a population by combining in-depth pedigree data with haploid markers. Each of these research aims will be discussed with examples of the human population in Flanders (Western Europe). At the end, we will discuss the advantages and pitfalls of using genetic genealogy within studies on human evolutionary genomics.

Detection of polygenic selection at different evolutionary levels (video)

Author(s): Excoffier L, Daub J

Summary:

Most approaches aiming at finding genes involved in adaptive events have focused on the detection of outlier loci, which resulted in the discovery of individually ´significant´ genes with strong effects. However, a collection of small effect mutations could have a large effect on a given biological pathway that includes many genes, and such a polygenic mode of adaptation has not been systematically investigated in humans or other mammals. We therefore propose to evidence polygenic selection by detecting signals of adaptation at the pathway or gene set level instead of analyzing single independent genes. Using a gene-set enrichment test, we identify genome-wide signals of recent adaptation among human populations as well as more ancient signals of adaptation in the human lineage and in primates.

A genome-wide scan for relaxation of constraints in the human lineage affecting specific functional processes (video)

Author(s): Somel, M, Wilson-Sayres, M, Jordan, G, Huerta-Sanchez, E, Fumagalli, M, Ferrer-Admetlla, A, Nielsen, R

Summary:

Changes in the subsistence mode of a species can lead to adaptive evolution of new functions, while it can also cause relaxed negative selection in previously essential functions. While positive selection in humans has been intensely studied, functional processes subject to relaxed constraints in the human lineage remain largely unknown. Here we present a framework for detecting relaxation of selective constraints that affect a particular functional process specifically in one taxon. Jointly using human and chimpanzee population genomic data with mammalian comparative genomic data, we identify olfactory receptors and proteasome subunits as candidates of relaxed constraints in humans: both gene sets contain high frequency non-synonymous mutations in humans while having conserved amino-acid sequences across other mammals. We further discuss the possible underlying causes of this signal.

Selection on penis size, body shape and height in humans: a simple multivariate method to quantify female preferences based on male physical attractiveness (video)

Author(s): Mautz, BS, Jennions, MD, Peters, RA, Wong, BBM

Summary:

Compelling evidence from many animal taxa indicates that male genitalia are often under post-copulatory sexual selection for characteristics that increase a male’s relative fertilization success under sperm competition. There could, however, also be direct pre-copulatory female mate choice based on male genital traits. Before clothing, the non-retractable human penis would have been conspicuous to potential mates. This, in combination with claims that humans have a large penis for their body size compared to other primates, has generated suggestions that human penis size partly evolved due to female choice. We presented women with digitally projected fully life-size, computer-generated animations of male figures to quantify the (interactive) effects of penis size, body shape and height on female assessment of male sexual attractiveness. We generated 343 male figures that each had one of seven possible values for each of the three test traits (7x7x7 = 343). All seven test values per trait were within two standard deviations of the mean based on a representative sample of males. We calculate response (fitness) surfaces based on the average attractiveness rank each of the 343 male figure received. We also calculated individual response surfaces for 105 women (each women viewed 53 figures). Both methods yielded almost identical results. We discuss our finding in the context of previous studies that have taken a univariate approach to quantify female preferences. We discuss the hypothesis that pre-copulatory sexual selection might play a role in the evolution of genital traits.

Quantitative genetic variation, selection and secular change of skull shape in humans

Author(s): Klingenberg, C, Martínez-Abadías, N, Esparza, M, Sjøvold, T, Hernández, M

Summary:

The combined use of geometric morphometrics and quantitative genetics provides a set of powerful tools for obtaining quantitative information that is crucial for many important questions concerning the evolution of shape. In particular, the demographic information that is available for human populations make humans a unique study system for studying the mechanisms of evolutionary change in morphological traits. We investigate skull shape in the population of Hallstatt (Austria), where a collection of human skulls with associated records offer a unique opportunity for such studies. We use an individual-based statistical model to estimate the genetic covariance matrix, and characterize selection using fitness estimates from demographic data. We find clear evidence for directional selection, but not for nonlinear selection (stabilizing or disruptive selection). The predicted response to this selection, computed with genetic parameters from the population, does not match the estimate of secular change over the 150-year range of the data. We discuss possible reasons for the mismatch.

Opportunity costs, intelligence, and criminality

Cognitive ability and the division of labor in urban ghettos: Evidence from gang activity in U.S. data

Hernstein and Murray (1994) famously argued that the division of labor in modern society is determined by individual differences in cognitive ability. This paper shows that differences in cognitive ability can also determine the division of labor in poor urban areas. We estimate the effect of IQ on time-to-first gang participation with data from the National Longitudinal Survey of Youth (NLSY97) and Project on Human Development in Chicago Neighborhoods (PHDCN). Results from both the NLSY97 and PHDCN indicate that low-IQ is a robust predictor of gang participation. There are two plausible explanations of this main finding: (1) low-IQ individuals may have comparative advantage in violence as their opportunity costs of engaging in legal activities are low and (2) gangs may prefer low-IQ individuals as a way to reduce agency costs. We find strong evidence in support of the hypothesis that persons with lower IQs have comparative advantage in criminal activity in the PHDCN dataset. Highlights

► This paper shows that cognitive ability can determine the division of labor in poor urban areas. ► We estimate the effect of IQ on time-to-first gang participation with data from U.S. data. ► Results indicate low-IQ is a robust predictor of gang participation. ► A person's relative IQ, with respect to one's neighborhood peers, determines gang participation.

Related posts:

• Can racial differences in circulating testosterone explain racial differences in crime?
• What explains racial differences in crime?
• More on race, crime, and intelligence
• Why criminals are less intelligent than non-criminals
• IQ, SES, and criminality

Intelligence and corruption

Intelligence and bribing behavior in a one-shot game

We investigate the relationship between intelligence and bribing behavior in a simple one-shot game of corruption. We find a robust relationship between intelligence and the probability of bribing in which a higher intelligence quotient (IQ) leads to a lower probability of bribing in the game. This result holds after controlling for other determinants such as gender, attitude toward corruption, and perceptions of corruption. By revealing the gender of the matched player, we also show that gender perceptions of corruption are strong determinants of bribery.

Intelligence and corruption

This study finds that countries with high-IQ populations enjoy less corruption. I propose that this is because intelligent people have longer time horizons.

(Via UDADISI.)

IQ, SES, and criminality

(Via Chuck.) Elaboration on the association between IQ and parental SES with subsequent crime. Personality and Individual Differences 50 (2011) 1233–1237. (pdf)

The current study, based on the nationally representative NLSY data, follows incarceration over a 24-year period. This represents the longest prospective examination of the NLSY crime data to date, since previous analyses have been shorter and is not prospective (Herrnstein & Murray, 1994). With the aim of providing greater confidence in the results, unlike prior analyses the current study uses three major criminological outcomes (onset, incidence and frequency of incarceration), and not one (incidence of incarceration). Based on theoretically reformulated associations between the study variables, the results show that low IQ, low parental SES and their interaction modestly predict the incidence of, frequency of and time to incarceration.

Theoretically, a low IQ may make coping and decision-making difficult and increase the likelihood of crime. Taken in isolation the association between low IQ and increased risk of crime in the current results may be taken as evidence that is consistent with the Bell Curve (Herrnstein & Murray, 1994). Concurrently, however, the present results also indicate that a low parental SES increases the risk of crime, potentially through an inadequate familial environment (Bradley & Corwyn, 2002). These family characteristics may include little emphasis on social attainment. Thus, the current findings indicate that the family environment may provide a route to influence the association between IQ and crime. This possibility is not considered in the Bell Curve view on crime that emphasizes neighborhood SES (Herrnstein & Murray, 1994), and is consistent with opponents to the Bell Curve (Fischer et al., 1996).

Collectively, however, the effects of IQ and parental SES on crime are modestly amplified, as captured by the interaction reflecting unfavorable conditions (i.e., particularly if both IQ and parental SES are low). A possible explanation of this interaction is that a disadvantaged home environment does not encourage social attainment and a low IQ makes coping and decision-making difficult. Taken together this increases the likelihood of crime. Thus these findings support an interactional perspective of crime. Their interpretation is consistent with the usually competing theoretical notions that contrast low SES (Fischer et al., 1996) or low IQ (Herrnstein & Murray, 1994) as factors that increase the likelihood of crime. [. . .]

This study does not separate genetic–environmental influences, unlike past research (e.g., Koenen, Caspi, Moffitt, Rijsdijk, & Taylor, 2006). SES may not purely be an environmental factor that is unrelated to IQ. Parents may give children both genes for IQ and SES (i.e., passive gene–environment associations), and a parent’s SES is partly based on their IQ as a result of life-long active gene–environment interactions. Accordingly, IQ and SES may be moderately correlated due to common genetic influences. Also, as the participants in this study mature, they become increasingly free to create their own environments, partly due to both IQ and SES. The current study, however, affords no assessment of genetics, or upward or downward social mobility, thereby highlighting key directions for future research.

Related posts:

• Can racial differences in circulating testosterone explain racial differences in crime?
• What explains racial differences in crime?
• More on race, crime, and intelligence
• Why criminals are less intelligent than non-criminals

IQ-height correlation partly attributable to pleiotropic genetic factors (not just cross-assortative mating)

The Genetic Correlation between Height and IQ: Shared Genes or Assortative Mating?

In this study, we modeled the covariation between monozygotic and dizygotic twins, their siblings, and their parents (total N = 7,905) to elucidate the nature of the correlation between two potentially sexually selected traits in humans: height and IQ. Unlike previous designs used to investigate the nature of the height–IQ correlation, the present design accounts for the effects of assortative mating and provides much less biased estimates of additive genetic, non-additive genetic, and shared environmental influences. Both traits were highly heritable, although there was greater evidence for non-additive genetic effects in males. After accounting for assortative mating, the correlation between height and IQ was found to be almost entirely genetic in nature. Model fits indicate that both pleiotropy and assortative mating contribute significantly and about equally to this genetic correlation. [. . .]

Taller people tend to be smarter. Although the relationship is modest, height and IQ are consistently correlated at ~.10–.20 [24], [25], [26]. [. . .]

The importance of genetic pleiotropy on the association between IQ and height is notable. On the surface, it might seem that height and IQ involve very different functional systems with different developmental origins. Genetic pleiotropy between IQ and height (indeed, between any two complex fitness traits) is consistent with the idea that variation in these traits partly reflects genome-wide mutational loads, and that these traits are components of attractiveness because of this—i.e., they are honest signals or cues of ‘good genes’ [43], [44], [45]. The additional and substantial increase in additive genetic covariance as a function of assortative mating is consistent with both traits being attractive to the opposite sex.

Related posts:

• Bodily symmetry: origins and lifecourse associations with cognition, personality, and status
• Brainy men, it seems, do have better sperm
• Physical correlates of cognitive ability

"De-Extinction" startup and embryo screening

"By reviving lost species, a new company could put a warm and fuzzy face on advanced reproductive engineering":

Two of biotechnology’s most prolific and far-sighted researchers say they’re teaming up to start a company that intends to rewrite the rules of animal reproduction.

The company, provisionally named Ark Corporation, is being cofounded by stem-cell pioneer Robert Lanza and Harvard Medical School DNA expert George Church. [. . .]

But here’s the deal: the very same biotechnologies needed to reanimate lost species are going to have far, far greater financial and social impact when they’re applied to commercial breeding of livestock, pets, and even humans. [. . .]

Ark’s key technology is going to be induced pluripotent stem cells, or iPS cells (see “Growing Heart Cells Just for You”). To make iPS cells, researchers take an ordinary skin cell and, by modifying it or adding certain chemicals, turn it into a potent stem cell that’s able to grow into any other tissue of the body, including eggs and sperm.

It’s exactly this ability to make sperm and eggs in the lab that opens the commercial possibilities Lanza and Church say their startup company will exploit. [. . .]

Beyond farm animals, iPS cells have even more mind-boggling possibilities in human reproduction. With this technology, it may be possible to create functional eggs and sperm for people who are infertile because of age or other issues.

Note that in the China Is Engineering Genius Babies stories statements like "embryo screening will allow parents to pick their brightest zygote and potentially bump up every generation's intelligence by five to 15 IQ points" refer to what's plausible with current IVF technology. Here, a relatively restricted number of embryos would be produced; they'd be sequenced or genotyped; and estimates of genomic IQ or other traits of interest would be used in choosing one or two of the embryos to implant. Again, there's nothing (beyond presently insufficient sample sizes) that prevents this from happening with our current understanding of genetics and existing reproductive technology.

Projecting forward very minimally, if it becomes possible to effectively and cheaply produce hundreds or thousands of eggs from skin cells, besides likely increasing the uptake of IVF with embryo screening by couples with normal fertility (ovarian hyperstimulation, etc., is not something I expect most women would rush to volunteer for in exchange for the promise their children will average 5 points higher in IQ) it should make possible much higher levels of selection per generation. A similar and potentially even greater increase in selective power might come from genetic screening of individual sperm cells prior to fertilization, which has now been demonstrated in mice. Beyond IQ, it should be similarly straightforward to select for any other heritable quantitative trait or for combinations of traits (height, longevity, physical ability, etc.).

"Common DNA Markers Can Account for More Than Half of the Genetic Influence on Cognitive Abilities"

A new paper from Robert Plomin (full text is free), reiterating a point that some are still failing to grasp:

For nearly a century, twin and adoption studies have yielded substantial estimates of heritability for cognitive abilities, although it has proved difficult for genomewide-association studies to identify the genetic variants that account for this heritability (i.e., the missing-heritability problem). However, a new approach, genomewide complex-trait analysis (GCTA), forgoes the identification of individual variants to estimate the total heritability captured by common DNA markers on genotyping arrays. In the same sample of 3,154 pairs of 12-year-old twins, we directly compared twin-study heritability estimates for cognitive abilities (language, verbal, nonverbal, and general) with GCTA estimates captured by 1.7 million DNA markers. We found that DNA markers tagged by the array accounted for .66 of the estimated heritability, reaffirming that cognitive abilities are heritable. Larger sample sizes alone will be sufficient to identify many of the genetic variants that influence cognitive abilities.

Contra confused people on twitter and elsewhere, one need not speculate about what the BGI study will or will not find. The Visscher study convincingly demonstrated a year and a half ago that breeding values for IQ could be estimated from SNP microarray data. No new technology or theoretical breakthroughs are required to capture most of the genetic component of IQ -- only larger sample sizes.

In summary, GCTA estimates confirmed about two thirds of twin-study estimates of heritability for cognitive abilities, using the same measures at the same age in the same sample. This finding implies that, with sufficiently large sample sizes, many genes associated with cognitive abilities can be identified using the common SNPs on current DNA arrays. Whole-genome sequencing might help to close the rest of the missing-heritability gap by identifying rare DNA variants that contribute to the heritability of cognitive abilities, although other possibilities remain, including the possibility that twin and adoption studies have overestimated heritability. GCTA might also mark the beginning of the end of the nature-nurture controversy because it is much more difficult to dispute DNA-based evidence for genetic influence than it is to question the results of twin and adoption studies.

Bodily symmetry: origins and lifecourse associations with cognition, personality, and status

A 2012 PhD thesis (pdf):

Symmetry – measured as the size asymmetry of a group of symmetrical body traits such as ear height or elbow circumference – has often been used as an index of the capacity to develop normally despite stress and correlates with a wide range of outcomes including intelligence, health and aspects of behaviour. [. . .] The present work advances the existing empirical literature in six separate domains. It also improves upon past methodology by using novel methods of digital measurement of asymmetry as well as for the first time digitally measuring endogenous asymmetry as indexed by the bones and linking bone asymmetry to intelligence. The research was conducted on four samples. [. . .] Firstly, a sample of elderly participants from the Lothian Birth Cohort 1921 (LBC1921, n = 216) tested around ages 11, 79, 83, and 87. Secondly, the Science Festival Sample (SFS), a group of children recruited at a public science event aged between 4 and 15 (n = 856). Thirdly, a group of Orkney residents aged 18 to 86 (the ORCADES, n = 1200). Fourthly the Berlin Sample (BS), a group of Berlin residents (n = 207) between 20 and 30 years old. In the LBC 1921, men with poorer socioeconomic status in childhood had higher facial asymmetry in old age ( = -.25, p = .03). While investigating issues related to asymmetry in the same sample it was found that relatively more severe digit curvature – a minor physical anomaly – was associated with relatively greater cognitive decline ( = -.19, p = .02). Within the SFS asymmetry decreased across human childhood ( = -.16, p = .01), and more asymmetrical children exhibited slower choice reaction times ( = .0.17, p = .002). In the ORCADES sample, the more asymmetrical participants (as indexed by bone asymmetry) were less intelligent ( = -.24, p = .01). In the Berlin Sample and the LBC 1921 no consistent associations were found between personality traits and asymmetry. Collectively, these findings suggest symmetry functions as a measure of overall well-being as the trend is for higher asymmetry to be associated with a relatively poorer score on a variety of outcome measures. The findings considerably expand the number of existing studies in these empirical areas and in several cases – particularly asymmetry’s association with socioeconomic status in the elderly and reaction times among children – represent the first work on those areas. The present work confirms the finding that asymmetry is linked to adverse outcomes. However, the underlying mechanisms by which symmetry is linked to such outcomes remain underexplored and require clarification.

Childhood intelligence is heritable, highly polygenic and associated with FNBP1L

New paper from Visscher, Deary, Plomin, and others, with results consistent with previous findings:

Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17 989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10(-15), 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10(-5)), 3.5% (P=10(-3)) and 0.5% (P=6 × 10(-5)) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance. Molecular Psychiatry advance online publication, 29 January 2013; doi:10.1038/mp.2012.184.

The Myth of American Meritocracy: How corrupt are Ivy League admissions?

Via Sailer. Note: the article is by Ron Unz, though in this case his numbers appear consistent with my own impressions and previous knowledge.

The Myth of American Meritocracy:

The evidence of the recent NMS semifinalist lists seems the most conclusive of all, given the huge statistical sample sizes involved. As discussed earlier, these students constitute roughly the highest 0.5 percent in academic ability, the top 16,000 high school seniors who should be enrolling at the Ivy League and America’s other most elite academic universities. In California, white Gentile names outnumber Jewish ones by over 8-to-1; in Texas, over 20-to-1; in Florida and Illinois, around 9-to-1. Even in New York, America’s most heavily Jewish state, there are more than two high-ability white Gentile students for every Jewish one. Based on the overall distribution of America’s population, it appears that approximately 65–70 percent of America’s highest ability students are non-Jewish whites, well over ten times the Jewish total of under 6 percent.

Needless to say, these proportions are considerably different from what we actually find among the admitted students at Harvard and its elite peers, which today serve as a direct funnel to the commanding heights of American academics, law, business, and finance. Based on reported statistics, Jews approximately match or even outnumber non-Jewish whites at Harvard and most of the other Ivy League schools, which seems wildly disproportionate. Indeed, the official statistics indicate that non-Jewish whites at Harvard are America’s most under-represented population group, enrolled at a much lower fraction of their national population than blacks or Hispanics, despite having far higher academic test scores. [. . .]

Just as striking as these wildly disproportionate current numbers have been the longer enrollment trends. In the three decades since I graduated Harvard, the presence of white Gentiles has dropped by as much as 70 percent, despite no remotely comparable decline in the relative size or academic performance of that population; meanwhile, the percentage of Jewish students has actually increased. This period certainly saw a very rapid rise in the number of Asian, Hispanic, and foreign students, as well as some increase in blacks. But it seems rather odd that all of these other gains would have come at the expense of whites of Christian background, and none at the expense of Jews.

Furthermore, the Harvard enrollment changes over the last decade have been even more unusual when we compare them to changes in the underlying demographics. Between 2000 and 2011, the relative percentage of college-age blacks enrolled at Harvard dropped by 18 percent, along with declines of 13 percent for Asians and 11 percent for Hispanics, while only whites increased, expanding their relative enrollment by 16 percent. However, this is merely an optical illusion: in fact, the figure for non-Jewish whites slightly declined, while the relative enrollment of Jews increased by over 35 percent, probably reaching the highest level in Harvard’s entire history. Thus, the relative presence of Jews rose sharply while that of all other groups declined, and this occurred during exactly the period when the once-remarkable academic performance of Jewish high school students seemed to suddenly collapse. [. . .]

Each year, the Ivy League colleges enroll almost 10,000 American whites and Asians, of whom over 3000 are Jewish. Meanwhile, each year the NMS Corporation selects and publicly names America’s highest-ability 16,000 graduating seniors; of these, fewer than 1000 are Jewish, while almost 15,000 are non-Jewish whites and Asians. Even if every single one of these high-ability Jewish students applied to and enrolled at the Ivy League—with none going to any of America’s other 3000 colleges—Ivy League admissions officers are obviously still dipping rather deep into the lower reaches of the Jewish ability-pool, instead of easily drawing from some 15,000 other publicly identified candidates of far greater ability but different ethnicity. [. . .]

The situation becomes even stranger when we focus on Harvard, which this year accepted fewer than 6 percent of over 34,000 applicants and whose offers of admission are seldom refused. Each Harvard class includes roughly 400 Jews and 800 Asians and non-Jewish whites; this total represents over 40 percent of America’s highest-ability Jewish students, but merely 5 percent of their equally high-ability non-Jewish peers. It is quite possible that a larger percentage of these top Jewish students apply and decide to attend than similar members from these other groups, but it seems wildly implausible that such causes could account for roughly an eight-fold difference in apparent admissions outcome. Harvard’s stated “holistic” admissions policy explicitly takes into account numerous personal characteristics other than straight academic ability, including sports and musical talent. But it seems very unlikely that any remotely neutral application of these principles could produce admissions results whose ethnic skew differs so widely from the underlying meritocratic ratios.

One datapoint strengthening this suspicion of admissions bias has been the plunge in the number of Harvard’s entering National Merit Scholars, a particularly select ability group, which dropped by almost 40 percent between 2002 and 2011, falling from 396 to 248. This exact period saw a collapse in Jewish academic achievement combined with a sharp rise in Jewish Harvard admissions, which together might easily help to explain Harvard’s strange decline in this important measure of highest student quality. [. . .]

It is important to note that these current rejection rates of top scoring applicants are vastly higher than during the 1950s or 1960s, when Harvard admitted six of every seven such students and Princeton adopted a 1959 policy in which no high scoring applicant could be refused admission without a detailed review by a faculty committee.78 An obvious indication of Karabel’s obtuseness is that he describes and condemns the anti-meritocratic policies of the past without apparently noticing that they have actually become far worse today. An admissions framework in which academic merit is not the prime consideration may be directly related to the mystery of why Harvard’s ethnic skew differs in such extreme fashion from that of America’s brightest graduating seniors. In fact, Harvard’s apparent preference for academically weak Jewish applicants seems to be reflected in their performance once they arrive on campus.79

Related: "Merit" in elite college admissions

Genetic architecture of intelligence from SNP distance measures

From a presentation by Steve Hsu (pdf slides):

Quantitative traits: many alleles, each of small effect. GWAS discovery of individual loci is hard.

But, phenotype differences must be associated with LARGE number of genetic differences.

Investigate pairwise genetic distance as g score (or height) are varied. Extract underlying genetic architecture:
1. Distribution of associated alleles dominated by small MAF (Minor Allele Frequency)
2. More (−) than (+) minor alleles (MAF < 0.5)
3. Rough estimate of 10k causal alleles in total [. . .]

Select outlier groups H and L. Averaging over pairs eliminates fluctuations in distance which are uncorrelated to phenotype.

Average pairwise genetic distance changes with mean IQ and IQ difference: ∼ 39 SNPs per population SD [. . .]

Low IQ = more rare (−) variants. Larger genetic distances between individuals. Similar results for height. [. . .]

Geniuses and Giants: Fewer deleterious alleles.

(A) 39 SNPs per SD of IQ suggests roughly 10k causal variants.

(B) Exceptional cognitive ability = of order 100’s fewer rare (−) variants than an average person.

Apropos of the last post, here's Hsu's comment when linking to these slides:

In the context of human genetics, it's clear there's plenty of room at the top -- possibly as much as +30 SDs based on existing variance in the human population! (Compare to the result of selection in maize.)

Nor does Hsu shrink from the practical implications:

Imagine what a couple might pay to ensure that they get the best out of 10 or 50 possible offspring, optimizing over their choice of heritable attributes. Compare this with the cost of a Harvard education or K-12 private school tuition. The cost of an IVF cycle is down to a few thousand dollars and could go even lower.

Genetic prediction at high accuracy will probably be possible once of order millions of genotype-phenotype data pairs are available for analysis. I predict about 5-10 years. The advance in the Nature article makes me confident that the necessary reproductive technologies will also be available.

I hope that progressive governments will make this procedure free for everyone. The benefits from increased economic output, decreased welfare and criminality rates, etc. far outweigh the cost of what I have described above ( = few cycles of IVF + running my algorithms provided at dirt cheap licensing rates ;-) [. . .]

You can't use US numbers for real medical costs -- our system has huge distortions. Few $K is the cost in Taiwan or Korea and success rates are if anything higher there. That's not even factoring the economies of scale that would arise if a large fraction of couples wanted it.

Who says the US is the first market for this?

No doubt Hsu is correct that Asia is unlikely to hesitate in applying the lessons of quantitative genetics to humans -- regardless of what Alexis Madrigal-types would have for the US. The Chinese government funds the genetics of intelligence study Hsu is involved in. Also see Hsu's slides from a previous talk (pdf):

THE FUTURE OF HUMAN INTELLIGENCE

• Suppose that we can non- destructively sequence gametes (sperm and egg cells).

• We can imagine parents choosing which gametes to unite in order to constitute their offspring.

• In particular, they might choose to unite gametes bearing many g-enhancing alleles. [. . .]

“Suppose we knew, for instance, twenty [loci affecting] mental characters. These would combine in over a million [homozygous] mental types. In practice each of these would naturally occur rather less frequently than one in a billion, or in a country like England, about once in 20,000 generations.

“It will give some idea as to the excellence of the best of these types when we consider that the Englishmen from Shakespeare to Darwin ... have occurred within ten generations; the thought of a race of men combining the illustrious qualities of these giants, and breeding true to them, is almost too overwhelming ...

“... but such a race will inevitably arise in whatever country first sees the inheritance of mental characters elucidated.”— RONALD A. FISHER, “MENDELISM AND BIOMETRY”

Haplogroups as evolutionary markers of cognitive ability

A reader emails a link (pdf) to a recent paper from Rindermann:

Studies investigating evolutionary theories on the origins of national differences in intelligence have been criticized on the basis that both national cognitive ability measures and supposedly evolutionarily informative proxies (such as latitude and climate) are confounded with general developmental status. In this study 14 Y chromosomal haplogroups (N = 47 countries) are employed as evolutionary markers. These are (most probably) not intelligence coding genes, but proxies of evolutionary development with potential relevance to cognitive ability. Correlations and regression analyses with a general developmental indicator (HDI) revealed that seven haplogroups were empirically important predictors of national cognitive ability (I, R1a, R1b, N, J1, E, T[+L]). Based on their evolutionary meaning and correlation with cognitive ability these haplogroups were grouped into two sets. Combined, they accounted in a regression and path analyses for 32–51% of the variance in national intelligence relative to the developmental indicator (35–58%). This pattern was replicated internationally with further controls (e.g. latitude, spatial autocorrelation etc.) and at the regional level in two independent samples (within Italy and Spain). These findings, using a conservative estimate of evolutionary influences, provide support for a mixed influence on national cognitive ability stemming from both current environmental and past environmental (evolutionary) factors.

The association with cognitive ability is positive for haplogroups I, R1a, R1b, and N and negative for J1, E, and T[+L], a pattern that also holds within Spain and Italy.

I1 arose in southern Scandinavia between 4000 and 6000 years ago (Rootsi et al., 2004). R1a and R1b arose in southwestern Asia (Caucasus, Pontic–Caspian steppe, Kurgan culture) around 22,000 ybp or somewhat later at 18,500 ybp. N and its relevant European subclades arose in Siberia and central Asia 12–27,000 ybp (Rootsi et al., 2007). This suggests that these environments may have been evolutionarily significant for cognitive ability: The presence of environmental harshness (i.e. extreme winter cold) suggests that factors relevant to the cold winters theory could have contributed to an increase in intelligence among the ancestors of those possessing these haplogroups. It is also likely that factors such as the development of agriculture, tools and dairy farming (milk from horses and cattle around 6000 ybp) were themselves an evolutionary catalyst for increasing cognitive ability (Cochran & Harpending, 2009; Hawks, Wang, Cochran, Harpending, & Moyzis, 2007; Wade, 2006), possibly enhancing neurological maturation via the provision of better nutrition during pregnancy, in youth and adulthood. The Neolithic transition to agriculture in cold climates would have been particularly evolutionarily demanding in terms of the need for heightened cognitive resources (e.g. farsightedness and planning).

[. . .]

Finally the steppe presents an unprotected environment, people living in such an environment are different to the people living in mountains, near to large oceans, in dense forests or in oases surrounded by large deserts, as they are permanently in danger of being attacked by neighboring peoples. This challenge could have selected for enhanced military preparedness a component of which may have been higher cognitive ability.

Ten Quite Interesting Things About Intelligence Test Scores - Prof. Ian Deary

"Doing research on intelligence is fascinating, and also sometimes frustrating. Like being a meteorologist, when you tell someone you work on intelligence you find that they start telling you about your own topic. So, Prof Ian Deary of the University of Edinburgh thinks that it is useful show people some real data that come from intelligence tests; opinions can then be founded on data, or at least one can query the data-gathering or its interpretations.

Without making assumptions about what intelligence tests measure or why people differ in their scores, he presents some results and invites people's reactions to them. He is still surprised by the fact that sitting down with one of these tests for three quarters of an hour or so and getting a score can have such far-reaching predictions, and cause so many arguments."

Daniel MacArthur twitter commentary from CSHL Personal Genomes meeting

This meeting took place a couple weeks ago -- dgmacarthur is presently posting from ICHG2011.

James Watson is asking a question. At least I think it's a question. #cshlpg
Yes, it was a question: hasn't ELSI just been a huge waste of money? Wait, no - he's back to talking again. #cshlpg

Manfred Kayser is talking about the genetics of human appearance, but his talk is untweetable. #cshlpg
Although Kayser's talk is untweetable it sounds as though a lot of this is close to publication - so stay tuned. #cshlpg

JV [Joris Veltman] discussing published analysis of de novo variants in mental retardation: http://bit.ly/olWpYK #cshlpg
JV: total number of de novo coding mutations is not higher in MR patients - but more likely to be in brain genes. #cshlpg

Deary / Visscher IQ paper

Those who read Sailer learned of this study a couple weeks ago. I've finally gotten around to looking at the actual paper, which seems convincing enough to me in doing what it says it does -- demonstrating "human intelligence is highly heritable and polygenic".

TGGP draws attention to comments by a blogger (Kevin Mitchell) who claims the paper "failed to establish the polygenic nature of the trait", but I don't see that Mitchell has a case. Mitchell:

I would interpret these findings very differently. What the authors do is analyse GWAS data in a very unusual way – they are not interested in finding specific SNPs affecting the trait, they simply use the SNPs to measure genetic relatedness between individuals.

As Mitchell then acknowledges, the paper does include a standard GWAS, the results of which are negative: at the level of individual SNPs not a single "replicable genome-wide significant association" is found. This is not surprising given the relatively small sample size and the (for me) expected polygenic nature of intelligence, but it (along with previous negative findings) tends to rule out any significant role for common variants of large effect in determining IQ.

The study uses SNPs across the genome to measure this relatedness and then shows it correlates with phenotypic similarity – i.e., the trait is heritable. We knew that already.

What they claim is that you can break down this effect by chromosome or by subregion. When they use the SNPs along longer chromosomes they seem to get a bigger effect – “explaining more of the phenotypic variance”. The inference is that thousands of SNPs, scattered across the whole genome, contribute to the trait or, more specifically to variance in the trait across the population (the implication is that they contribute to the value of the trait in individuals).

There is an alternative explanation for this effect, however, which is that using more SNPs simply gives a better estimate of genetic relatedness. So, the SNPs on chromosomes 1 (the longest) give a better estimate than those on chromosome 21 (the shortest) – they index relatedness with more precision. As a result, they correlate better with phenotypic similarity – this looks like you have “explained more of the variance”. In fact, getting such a signal from SNPs on chromosome 1 does not mean that any of the causal variants are actually on chromosome 1. Nor does the fact that such signals can be derived from anywhere in the genome mean that there are thousands of variants across the genome affecting the trait.

What Mitchell is claiming here is that the results could be explained by cryptic relatedness and/or population structure. However, the researchers address both issues, by excluding samples that appear to be related to other samples nearer than the level of 4th cousins and by including as covariates in their models the first few components of an MDS analysis. For non-close relatives in unstructured populations, how similar two individuals are on chromosome 1 tells us nothing about how similar they are on any other chromosome. Visscher was more explicit on this point in a commentary on the height paper:

What is the evidence that population structure is not causing the observed effects?

We took several steps to avoid population structure inflating the estimate of the variance explained by the SNPs. We excluded one individual from any pair that had an estimated relationship > 0.025 (approximately equivalent to between 3rd and 4th cousins). We fitted the first 20 principal components from the relationship matrix in the statistical model so that any population substructure that they picked up was excluded from the variance explained by the SNPs. Critically, we then estimated the correlation between the relationship matrices estimated from different chromosomes and did not find significant correlation. We tested a set of SNPs that are ancestry-informative in Europe for association with height and did not observe inflation of the test-statistics.

For the purpose of this paper, we performed an additional simulation experiment (inspired by comments from Dan Stram) by assuming that the causal variants were all carried on one set of chromosomes (odd numbers) and another set of chromosomes (even numbers) carried SNPs from which we estimated relatedness. If there is structure in the population then this would imply that a pair of individuals that are closely related on odd chromosomes will also be closely related on even chromosomes. We used the observed genotype data of 3,925 individuals and 295K SNPs as the basis of the simulation, and simulated 1,000 causal variants on the odd chromosomes with a total heritability of 80%. Then we performed a restricted maximum likelihood (REML) analysis of the simulated phenotypes on the genetic relationship matrix estimated from the SNPs on the even chromosomes. The estimates and standard errors (SEs) from 10 simulation replicates are shown in Table 1. Since REML estimates of variance are always positive, if the true variance explained is zero, we expect half the replicates to return an estimate of 0.0 and half to return an estimate with mean value 0.8 times the standard error. This is exactly what happened. Therefore we conclude (again) that there is no structure in the data that would inflate the estimate of the variance explained by the SNPs.

Steve Hsu correctly points out:

If I understand correctly, you want to claim that the observed population variation could be due to a few rare variants of large effect. But then it would be surprising for this study to have found .5 of the total variation to be associated with SNPs — compare to earlier studies using twins/adoptions/siblings that found narrow sense heritability of about .6 or so. I would not expect the rare alleles you hypothesize to be in good LD with SNPs (which are designed to tag common variants), so we would expect to lose a big chunk of the .6 additive heritability.

For example, in the Visscher paper on height they had to hand wave about imperfect LD to recover the full .8 or so of heritability. In this case the global fit comes out very close to .6, which suggests common rather than rare variants (at least, they are well tagged by SNPs). But if they are common variants their individual effect sizes must be small and there are a lot of them. Let me know if I am missing something.

Mitchell:

I don’t think the population variation is caused by “a few” rare variants – I think it is (or could be at least) caused by a larger number of rare variants – different ones in different people.

This is getting to be a pretty silly argument: "different ones in different people" would add up to a very large number, which sounds "polygenic" enough to me (regardless of how many people have the major allele at most variable sites). And again: rare variants will be tagged less effectively (if at all) by common SNPs, so the causal variants whose effects are being estimated in this study can't be too rare. The contribution of rare variants to variability in intelligence is likely largely on top of the effect identified here, and probably mostly negative: an unusually high number of rare, deleterious mutations will tend to interfere with brain development and diminish IQ; an unusually low number will result in a higher IQ on average, explaining at least in part the associations commonly found between intelligence and other markers of "good genes" (health, physical attractiveness, and so on). A priori, though, it makes no sense to expect this type of variation to be the only or overwhelming source of genetic variability in IQ. Clearly, a very large number of genes affect brain development, and I expect pretty much all of these genes to be polymorphic. It's also clear tradeoffs affecting IQ exist (such as between brain size and energy expenditure) and that specific IQ-influencing alleles will have varying effects on fitness in different times and places. So it seems obvious to me common variants should be expected to play a major role in inter-individual and inter-population IQ differences.

Incidentally, looking again at the supplementary material for the height paper recently, I noticed the following addition:

In the version of this supplementary file originally posted online, Supplementary Fig. 2a and 2b were incorrect. The legend stated that in Supplementary Fig. 2a, PC1 versus PC2 was plotted when in fact PC2 versus PC3 was shown. Similarly, in Supplementary Fig. 2b, PC4 versus PC5 was plotted rather than PC3 versus PC4 as stated. This error is purely graphical and does not in any way affect the results or conclusions presented in the article.

Dasein spotted the strange-looking PCA at the time. I didn't think it materially affected that paper's conclusion, but I'm pleased to see that confirmed and the issue resolved.

"Thousands" of genes influence intelligence

A commenter writes: "Robert Plomin and colleagues have apparently found some IQ genes". From the story:

SCIENTISTS have identified more than 200 genes potentially associated with academic performance in schoolchildren. [. . .]

The finding emerged from a study of more than 4000 British children to pinpoint the genes and genetic combinations that influence reasoning skills and general intelligence.

One of its main conclusions is that intelligence is controlled by a network of thousands of genes with each making just a small contribution to overall intelligence, rather than the handful of powerful genes that scientists once predicted.

So much for the fantasies of certain technorapturist HBDers that genetic engineering will erase racial differences in intelligence within a few decades.