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”

The Atlantic: How Eugenic Breeding Transformed the Dairy Industry

The Perfect Milk Machine: How Big Data Transformed the Dairy Industry:

There is a reason, of course, that the semen that Badger-Bluff Fanny Freddie produces has become such a hot commodity in what one artificial-insemination company calls "today's fast paced cattle semen market." In January of 2009, before he had a single daughter producing milk, the United States Department of Agriculture took a look at his lineage and more than 50,000 markers on his genome and declared him the best bull in the land. And, three years and 346 milk- and data-providing daughters later, it turns out that they were right. [. . .]

No matter how you apportion the praise or blame, the net effect is the same. Thousands of years of qualitative breeding on family-run farms begat cows producing a few thousand pounds of milk in their lifetimes; a mere 70 years of quantitative breeding optimized to suit corporate imperatives quadrupled what all previous civilization had accomplished. And the crazy thing is, we're at the cusp of a new era in which genomic data starts to compress the cycle of trait improvement, accelerating our path towards the perfect milk-production machine, also known as the Holstein dairy cow. [. . .]

"Animal breeders for many decades have used models that assume most traits are influenced by thousands of genes with very small effects. Some [individual] genes do have detectable effects, but many studies of plant and animal traits conclude that most of the genetic variation is from many little effects."

For dairy cows -- or humans, for that matter -- it's just not as simple as the dominant-recessive single-gene paradigm that Mendel created. In fact, Mendel picked his model organism well. Its simplicity allowed him to focus in on the simplest possible genetic model and figure it out. He could easily manipulate the plant breeding; he could observe key traits of the plant; and these traits happened to be controlled by a single gene, so the math lay within human computational range. Pea plants were perfect for studying the basics of genetics.

With that in mind, allow me to suggest, then, that the dairy farmers of America, and the geneticists who work with them, are the Mendels of the genomic age. That makes the dairy cow the pea plant of this exciting new time in biology. Last week in the Proceedings of the National Academy of Science, two of the most successful bulls of all time had their genomes published.

This is a landmark in dairy herd genomics, but it's most significant as a sign that while genomics remains mostly a curiosity for humans, it's already coming of age when it comes to cattle. It's telling that the cutting-edge genomics company Illumina has precisely one applied market: animal science. They make a chip that measures 50,000 markers on the cow genome for attributes that control the economically important functions of those animals. [. . .]

Mendel may have worked with plants, the rules he revealed turned out to be universal for all living things. The same could be true of the statistical rules that dairy scientists are learning about how to match up genomic data with the physical attributes they generate. The statistical rules that reflect the way dozens or hundreds of genes come together to make a cow likely to develop mastitis, say, may be formally similar to the rules that govern what makes people susceptible to schizophrenia or prone to living for a long time. Researchers like the University of Queensland's Peter Visscher are bringing the lessons of animal science to bear on our favorite animal, ourselves.

Want to live for a very long time? Well, we hope to discover the group of genes that are responsible for longevity. The problem is that you have genomic data over here and you have phenotypic data, i.e. how things actually are, over there. What you need, then, is some way of translating between these two realms. And it's that matrix, that series of transformations, that animal scientists have been working on for the past decade.

And this is as deep as the author of this piece, Alexis Madrigal, gets into the "lessons of animal science" for humans. Predict lifespan and disease risk. But don't allow yourself to imagine this sort of information might have any more direct uses or implications for humans. Breathlessly promoting genetic betterment of cows in one article; mouthing sentiments like this in another:

Ever since humans deduced the powerful nature of DNA and all the associated molecules that do work in our cells, people have wondered: how long before we can simply change our own genes? On the one hand, all kinds of genetic diseases could be cured. On the dark side, if genetics sets the limits of human action, how long before we create genetically enhanced humans? And, like many things in bioethics, these thoughts are never very far away from the long shadow of the Nazis' eugenics program.

Selection for height in Northern Europeans

Evidence of widespread selection on standing variation in Europe at height-associated SNPs:

Strong signatures of positive selection at newly arising genetic variants are well documented in humans1, 2, 3, 4, 5, 6, 7, 8, but this form of selection may not be widespread in recent human evolution9. Because many human traits are highly polygenic and partly determined by common, ancient genetic variation, an alternative model for rapid genetic adaptation has been proposed: weak selection acting on many pre-existing (standing) genetic variants, or polygenic adaptation10, 11, 12. By studying height, a classic polygenic trait, we demonstrate the first human signature of widespread selection on standing variation. We show that frequencies of alleles associated with increased height, both at known loci and genome wide, are systematically elevated in Northern Europeans compared with Southern Europeans (P < 4.3 × 10−4). This pattern mirrors intra-European height differences and is not confounded by ancestry or other ascertainment biases. The systematic frequency differences are consistent with the presence of widespread weak selection (selection coefficients ~10−3–10−5 per allele) rather than genetic drift alone (P < 10−15).

Luke Jostins described this research last year:

Europeans differ systematically in their height, and these differences correlate with latitude. The average Italian is 171cm, whereas the average Swede is a full 4cm taller. Are these differences genetic? Have they been under evolutionary selection in recent human history?

Michael Turchin gave some pretty convincing answers to these questions, using genetic data from the 129 thousand individuals in the GIANT consortium. He compared the frequencies of alleles that are known to increase height, and found that they are more common in Northern Europe. Interestingly, he found the same relationship for alleles that have weaker evidence for height association, showing that there are still a large number of common height variants hiding in the genome, which are also more frequent in Northern Europe.

Height differences are thus heritable, but have they been under evolutionary selection? Or are these differences merely down to genetic drift? This can also be tested using the GIANT data, which shows significant statistical evidence of selection on height variants in recent history. On top of that, the magnitude of the selection is correlated with the effect size of the height variant, providing strong evidence that these variants are being selected specifically for their impact on height.

This is a textbook example of how an evolutionary study should be done; you show a phenotypic difference exists, that it is heritable, and that it is under selection. This opens the question as to why height has been selected in Northern Europe (or shortness in Southern Europe). Could the same data be used to test specific hypotheses there?

Update on Androgen Receptor gene

An Encore for the Repeats: New Insights into an Old Genetic Variant

It is commonly accepted that the length of the polyQ tract influences the transactivation capacity of the receptor in an inverse manner; that is, the longer the tract, the lower the activity. To support this hypothesis, a clear negative impact on AR activity is documented in relationship with pathological expansions of the repeat length (40 or more), known as the Kennedy syndrome (5). This syndrome is characterized by spinobulbar muscular atrophy and hypoandrogenism due to partial androgen insensitivity. On the other hand, controversies still exist about the effect of variations in polyQ within the normal polymorphic range. The normal distribution of the (CAG)n is reported as 6–39 repeats, with a median of 21–22 in White Caucasian, 19–20 in African-American, 22–23 in Asian, and 23 in Hispanic populations. Clinical observations showing a linear correlation between testosterone level and CAG repeat length support the notion of a functional effect of the polymorphism within the normal range. In fact, increased circulating testosterone and estradiol levels in men with a higher number of CAG repeats can be considered as a compensatory mechanism aimed to overcome the weaker AR activity (6, 7). However, such a linear correlation has not been clearly demonstrated by in vitro experiments. The first two functional studies reported that the longest tract (Q31) displayed lower activity when compared with the shortest one (Q15). However, no significant differences were observed by comparing these two types of alleles to an intermediate number of CAG repeats (20 or 24) (8, 9). Quite strikingly, two recent articles provided evidence for the lack of a stepwise reduction in activity with increasing CAG length across the polymorphic range (10, 11). The reporter gene assay with three different CAG lengths (16, 22, and 28) has indeed shown the highest AR activity in the presence of 22 CAG repeats(10). The other study, performed in a human prostate tumor cell model, has provided mechanistic insights into how both increased and decreased polyQ allele length may negatively affect receptor function (11). This study has revealed a critical polyglutamine size (Q16-Q29) for optimal androgen-induced AR signaling, which corresponds to 91–99% of AR alleles within different ethnic groups. These novel in vitro findings have introduced a new concept for the analysis of AR-CAG repeat length in relationship to AR-related diseases, indicating that linear regression models are likely to be inappropriate.

The study by Davis-Dao et al. (12) indicates a disadvantage only in the case of short CAG repeats; however, upcoming investigations will probably shed light on whether the “optimal range” hypothesis can be applied also to this specific pathological context. In fact, the stratified analysis of nearly 4000 subjects, included in articles dealing with male infertility and AR-CAG length, has provided clinical evidence for the potential benefit of a CAG range corresponding to 22–23 triplets in spermatogenesis (24). However, it must be taken into consideration that this specific range may not be the same across different ethnic groups and may even vary in different tissues because the effect of polyQ repeat on transactivation is cell specific, presumably due to distinct profiles of coregulator proteins (11). Moreover, it is possible that spermatogenesis, more than the process of testis descent, depends predominantly on the genomic action of androgens, and thus on the direct consequence of the CAG length on transactivation. Clearly, more functional studies are needed for the interpretation of clinical data in different types of androgen-dependent diseases.

That blacks average fewer AR-CAG repeats has been held up as evidence blacks are more "masculinized". I was unconvinced one could draw that conclusion even accepting an inverse relationship between CAG repeat length and AR activity (since the CAG repeat represents only one link in androgen-related pathways, and there may be any number of other racial differences in relevant genes). Now it appears that compared to blacks, whites may in fact be more likely to have "optimal" CAG repeat lengths.

In addition, variation in another polymorphism of the AR gene, GGN repeat length, could conceivably lower AR activity in blacks relative to whites:

Short GGN repeats seem to be associated with decreased semen volume, possibly due to suboptimal AR activity. ["Androgen receptor gene GGN repeat length and reproductive characteristics in young Swedish men"]

Contrary to previously published data from Caucasians and Asian populations, which have the 2 by far most common GGN alleles of 23 and 24 in the former, and 21 and 22 in the latter, we found 4 common alleles of 20, 21, 22, and 23 in our study population with the highest frequency of 20 GGN allele followed by 22, 21 and 23 (GGN)n (Fig. 2). ["Androgen receptor gene CAG and GGN polymorphisms in infertile Nigerian men"]

Some more background from the first article above:

Throughout the human genome there are trinucleotide repeat sequences susceptible to either expansion or contraction during replication, giving rise to length polymorphisms in the general population. The polymorphic CAG repeat, which encodes an uninterrupted polyglutamine (polyQ) tract in the N-terminal transactivation domain of the androgen receptor (AR), is the most extensively studied genetic variant in individuals with disorders of the male reproductive system.

Despite an impressive number of studies, the pathogenic role of this polymorphism and its clinical relevance are still a matter of debate. Although a recent meta-analysis of 33 publications (1) supports a pathogenetic role for longer polyQ length in male infertility, the authors conclude their work stating that there is a need for new, well-designed studies (1). In fact, available data do not allow us to establish what range of AR-CAG repeat lengths predisposes impaired sperm production or to estimate the entity of the associated risk (1). Similar to other genetic variants, the literature related to CAG repeats suffers from an abundance in conflicting case-control association studies and a paucity of functional data (2). There are several plausible explanations for these apparent controversies, mostly related to: 1) poor study design (inappropriate selection of patients and controls, particularly with respect to their phenotype and their ethnic/geographic origin, and underpowered size of the study population); and 2) intrinsic complexity of the interaction between the AR and its endogenous/environmental ligands. An additional intricacy derives from the presence of another polymorphic trinucleotide repeat, (GGN)n, in the first exon of the AR gene, which may modulate the functional effect of the CAG repeat length, stressing the need for a combined analysis of the two AR polymorphisms (3, 4).

"Small is Beautiful: Genetic Studies in the Founder Population of Iceland"

Reports on a talk at the 1000 Genomes Project meeting a couple days ago:

13 Jul Nicolas Robine Nicolas Robine ?@notSoJunkDNA Augustine Kong (deCode Genetics) at #1000genomes

13 Jul Karol Estrada Karol Estrada ?@karls_es Augustine Kong: deCode has genotyped 100,000 samples, and whole-genome sequenced 2,200 samples #1000genomes

13 Jul Nicolas Robine Nicolas Robine ?@notSoJunkDNA AK: 100k chip-typed individuas to study "recombination as a phenotype", and examine "transmission distortion" #1000genomes

13 Jul Goncalo Abecasis Goncalo Abecasis ?@gabecasis Augustine Kong talks about gene mapping in Iceland. A population that is just the right size. Definitely not too small. #1000genomes

13 Jul Karol Estrada Karol Estrada ?@karls_es AK: imputations with 2200 seq. individuals have high accuracy (r^2>0.90 for variants down to 0.1%! #1000genomes

13 Jul Goncalo Abecasis Goncalo Abecasis ?@gabecasis AK: Rate of mutation doubles with every 16 year increase in paternal age. #1000genomes

13 Jul Karol Estrada Karol Estrada ?@karls_es AK: Genomic segments of Norwegian ancestry have 8 fold more singletons than average in deCode's dataset #1000genomes

Alex Forrest-Hay ?@aforre #1000genomes Augustine Kong: 400k SNPs would cover the Icelandic genome sufficiently to enable accurate imputation

Interview with Kari Stefansson:

We have sequenced the whole genomes of 2,500 people. We have genotyped about 120,000 Icelanders with an Illumina chip. We can impute whole genome sequence down to variants with less than 0.1% frequency into about 370,000 Icelanders -- there are only 320,000 living today!”

“We basically have the whole genome sequence of an entire nation.”

Margaret Sanger as Yankee utopian progressive

Margaret Sanger, daughter of Irish Catholics; married first to a Jew; then to a South African; influenced by and conduit of happenings in Europe; also, a "Yankee" and proof that "progressivism" is best conceived of as an offshoot of New England Puritanism.

More of an activist than her father, Bill had recently joined a Socialist Party local in the Bronx, where he lived with his father, Edward Ely Sanger; his mother, Henrietta Wolfberg; and his younger sister, Cecilia. Most heretically appealing for the rebellious daughter of a Catholic from a town without a synagogue, William Sanger was a Jew--by heritage, not conviction.

The Sangers had emigrated from Berlin in 1878 when William was four years old. His father represented a growing stream of Jewish immigrants from Germany as well as, in greater numbers, Eastern Europe, pushed across the Atlantic by increasing pressure from the Prussian state. When the census taker came to their apartment in the Nineteenth Ward two years after their arrival, in 1880, Bill Sanger's father gave his name as Edward, a proper Anglo-Saxon name, and his occupation as a wool manufacturer. Twenty years later, living in a diverse neighborhood of mostly German Jews who sold real estate and insurance, he was listed as Elzia, an unusual contraction of the Hebrew name Eleazar.

At first, Maggie Higgins and Bill Sanger shared their alien status: she the migratory, rebellious daughter of a poor Catholic family, he a Jewish immigrant still living at home at twenty-six years of age. The, for the rest of their lives, they both obscured the facts of his family heritage, which became easier to do when his father died in 1903. Finding Bill's background exotic at first, she later erased it, lest it compromise the fragile birth control movement and her credibility to lead it. To be married to a Jew in the first decades of the twentieth century was to be associated with the radical political views of socialists and to invite the pervasive smear of anti-Semitism. [. . .]

In her Autobiography, Margaret Sanger transformed her father-in-law, Elzia, a wool manufacturer in the garment industry in New York, into Edward, a wealthy English sheep rancher who had moved to Australia. During one of his trips to Europe, through he was sixteen years her senior, Edward had fallen in love with the mayor Konigsberg's fourteen-year-old daughter, Henrietta. Smitten, he had waited for her to grow up and then returned to marry her.

[Jean H. Baker. Margaret Sanger: A Life of Passion]

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.

John Hawks intro physical anthropology course

Principles of Biological Anthropology. This has been up for a while, but apparently Hawks may be removing the videos in the near future, so watch soon if interested.

Hawks also has a teaching company course.

Michael Hammer on archaic admixture in Africa

Open thread (8)

Links, off-topic discussion, etc. Previous open threads: 1 2 3 4 5 6 7

Men With Wider Faces Are More Generous to Their In-Group When Out-Group Competition Is Salient

Face Structure Predicts Cooperation: Men With Wider Faces Are More Generous to Their In-Group When Out-Group Competition Is Salient (abstract):

Male facial width-to-height ratio appears to correlate with antisocial tendencies, such as aggression, exploitation, cheating, and deception. We present evidence that male facial width-to-height ratio is also associated with a stereotypically male prosocial tendency: to increase cooperation with other in-group members during intergroup competition. We found that men who had wider faces, compared with men who had narrower faces, showed more self-sacrificing cooperation to help their group members when there was competition with another group. We propose that this finding makes sense given the evolutionary functions of social helpfulness and aggression.

Evolution and the psychology of intergroup conflict: the male warrior hypothesis

Free pdf here:

Evolution and the psychology of intergroup conflict: the male warrior hypothesis
Melissa M. McDonald1,*,
Carlos David Navarrete1 and
Mark Van Vugt2,3

The social science literature contains numerous examples of human tribalism and parochialism—the tendency to categorize individuals on the basis of their group membership, and treat ingroup members benevolently and outgroup members malevolently. We hypothesize that this tribal inclination is an adaptive response to the threat of coalitional aggression and intergroup conflict perpetrated by ‘warrior males’ in both ancestral and modern human environments. Here, we describe how male coalitional aggression could have affected the social psychologies of men and women differently and present preliminary evidence from experimental social psychological studies testing various predictions from the ‘male warrior’ hypothesis. Finally, we discuss the theoretical implications of our research for studying intergroup relations both in humans and non-humans and discuss some practical implications.

TEDxCambridge: George Church on genomics and human diversity

"George Church considers recent advances in genomics and personalized medicine and asks: as we seek to eliminate disorders like schizophrenia and dyslexia, or even rare genetic diseases, how should we think about preserving human diversity?"

Slide at 7:20:

"Rare [does not necessarily equal] Deleterious

MSTN: Lean muscles
LRP5: Extra-strong bones
PCSK9: Greatly reduced risk of heart disease
CCR5: Virus-resistance

Embrace the extremes: informative, easy, powerful"

Conclusion: "So anyway we and others are sequencing these long-lived animals and humans and we hope this will be part of a bigger project to measure and design humans going forward."

Eske Willerslev at the 2012 DOE JGI Genomics of Energy and Environment Meeting

'Eske Willerslev from the University of Copenhagen on "Understanding Historical Human Migration Patterns and Interbreeding Using the Ancient Genomes of a Palaeo-Eskimo and an Aboriginal Australian" at the 7th Annual Genomics of Energy & Environment Meeting on March 21, 2012 in Walnut Creek, Calif.'

"Asians are closer to Europeans than they are to aboriginal Australians, but at the same time aborigine Australians are closer to Asians than they are to Europeans." (23:10)

At the end, Willerslev mentions "we are also doing the genome of Clovis, the oldest skeleton in the Americas". I have no idea which skeleton in particular he's talking about, but any Paleo-Indian genome should be informative.

New York Times science writer Carl Zimmer: Oetzi genome "not important"

Ken Weiss links to this speech by Carl Zimmer.

"As I recall, the big news in the Oetzi genome I think was that he had brown eyes. I mean it just . . . it doesn't . . . that's not important." (31:42)

Obviously, that was not the biggest news to those who were paying attention. But even if it had been, I'd still be taken aback by a comment like this from a science reporter. In fairness, Zimmer's talk overall is reasonable and inoffensive compared to Weiss's blog post, and does not appear to be motivated by the same racial anxieties:

So just to conclude I would say that my experience in writing about genomes has firmly convinced me that we are in the middle of another scientific revolution like the one in the middle of the 17th century and that genomes are a big part of that. But it's important to focus on what makes that revolution so important. So in the 1600s, for example, one of the most important things that happened was the people invented microscopes. [. . .] But again it wasn't so much the microscopes themselves that mattered, but what people were seeing with them.

Some asshole named "Ken Weiss" wants whole genome sequencing to go away

Is whole genome sequencing fading? Will it rebound (or relapse)?

There are various informal indicators that funders are losing enthusiasm for human whole genome sequencing. [. . .] If this turns out to be more than a few anecdotes or personal opinions, and is actually occurring, it's understandable and to be lauded. As we think we can truthfully claim, we have for years been warning of the dangers of the kind of overkill that genomics (and, indeed, other 'omics' fads) present: promise miracles and you had better deliver!

The same thing applies to evolutionary studies that seek whole genome sequences as well as to studies designed to use such data to predict individual diseases. There are too many variants to sort through, the individual signal is too weak, and too many parts of the genome contribute to many if not most traits, for genomes to be all that important--whether for predicting future disease, normal phenotypes like behaviors, or fitness in the face of natural selection.

The proper response to genomic complexity is of course not to throw ones hands up and go back to candidate gene studies, but to sequence lots and lots of genomes in full. This is what needs to happen, and falling sequencing costs mean this is what will happen, regardless of what Ken Weiss wants.

Note: Ken Weiss is "Evan Pugh Professor of Anthropology and Genetics at Penn State University". I can think of a few possibilities: (1) Weiss is sincere in believing medical science and evolutionary research would be better advanced with less whole genome sequencing; he's not malicious -- just short-sighted, unimaginative, and breathtakingly ignorant of the broader state of his supposed academic specialty. (2) Weiss is merely jealous that his colleagues are getting bigger grants than him, a frailty he could perhaps be forgiven. (3) "Anthropology and Genetics" professor Weiss, for some reason, prefers that human evolutionary and genetics research not advance.

Looking at some of his other posts, I see plenty of evidence ethnic and/or ideological considerations underpin Weiss's "warnings" about genomics.

Analysis of surname origins identifies genetic admixture events undetectable from genealogical records

In the name of the migrant father—Analysis of surname origins identifies genetic admixture events undetectable from genealogical records

M H D Larmuseau et al.

Patrilineal heritable surnames are widely used to select autochthonous participants for studies on small-scale population genetic patterns owing to the unique link between the surname and a genetic marker, the Y-chromosome (Y-chr). Today, the question arises as to whether the surname origin will be informative on top of in-depth genealogical pedigrees. Admixture events that happened in the period after giving heritable surnames but before the start of genealogical records may be informative about the additional value of the surname origin. In this context, an interesting historical event is the demic migration from French-speaking regions in Northern France to the depopulated and Dutch-speaking region Flanders at the end of the sixteenth century. Y-chr subhaplogroups of individuals with a French/Roman surname that could be associated with this migration event were compared with those of a group with autochthonous Flemish surnames. Although these groups could not be differentiated based on in-depth genealogical data, they were significantly genetically different from each other. Moreover, the observed genetic divergence was related to the differences in the distributions of main Y-subhaplogroups between contemporary populations from Northern France and Flanders. Therefore, these results indicate that the surname origin can be an important feature on top of in-depth genealogical results to select autochthonous participants for a regional population genetic study based on Y-chromosomes.

Keywords: admixture; genetic genealogy; historical gene flow; human population structure; Y-chromosome

http://www.nature.com/hdy/journal/vaop/ncurrent/abs/hdy201217a.html

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."

Miscellaneous links

Larger monkey groups lose fights because they contain more deserters

In the Battle of Rorke’s Drift, 150 or so British troops defended a mission station against thousands of Zulu warriors. At the Battle of Thermopylae, around 7,000 Greeks successfully held back a Persian army of hundreds of thousands for seven days. Human history has many examples of a small force defeating or holding their own against a much larger one. Among animals too, the underdogs often become the victors. One such example exists in the rainforests of Panama. There, capuchin monkeys live in large groups, each with its own territory. The monkeys often invade each other’s land. Numbers provide an obvious advantage in such conflicts, but small groups can often successfully defend their territory against big ones. Unlike human underdogs, they don’t win because of superior tactics or weapons. They win because their rivals are full of deserters.

Whole genome sequences of a male and female supercentenarian, ages greater than 114 years

We show that: (1) the sequence variant spectrum of these two individuals’ DNA sequences is largely comparable to existing non-supercentenarian genomes; (2) the two individuals do not appear to carry most of the well-established human longevity enabling variants already reported in the literature; (3) they have a comparable number of known disease-associated variants relative to most human genomes sequenced to-date;

Comparison of measures of marker informativeness for ancestry and admixture mapping.

BACKGROUND: Admixture mapping is a powerful gene mapping approach for an admixed population formed from ancestral populations with different allele frequencies. The power of this method relies on the ability of ancestry informative markers (AIMs) to infer ancestry along the chromosomes of admixed individuals. In this study, more than one million SNPs from HapMap databases have been interrogated in an admixed populations using various measures of ancestry informativeness: Fisher Information Content (FIC), Shannon Information Content (SIC), F statistics (FST), Informativeness for Assignment Measure (In), and the Absolute Allele Frequency Differences (delta). The objectives are to compare these measures of informativeness to select SNP markers for ancestry inference, and to determine the accuracy of AIM panels selected by each measure in estimating the contributions of the ancestors to the admixed population. RESULTS: FST and In had the highest Spearman correlation and the best agreement as measured by Kappa statistics based on deciles. Although the different measures of marker informativeness performed comparably well, analyses based on the top 1 to 10% ranked informative markers of simulated data showed that In was better in estimating ancestry for an admixed population. CONCLUSIONS: Although millions of SNPs have been identified, only a small subset needs to be genotyped in order to accurately predict ancestry with a minimal error rate in a cost-effective manner. In this article, we compared various methods for selecting ancestry informative SNPs using simulations as well as SNP genotype data from samples of admixed populations and showed that the In measure estimates ancestry proportion (in an admixed population) with lower bias and mean square error.

Fluid insight moderates the relationship between psychoticism and crystallized intelligence

To elucidate potential relationships between personality and intelligence it is necessary to move beyond the ad hoc reporting of correlation coefficients and focus instead on testing deductions from well established theories. To this end the present paper references Eysenck’s (1995) theoretical work linking the dimension of psychoticism to both psychosis and creative genius. Drawing on this theory it was argued that the relationship between psychoticism and crystallized ability will be conditional on the level of fluid intelligence. Participants (N = 100) completed the Eysenck Personality Questionnaire-Revised (EPQ-R) and the Kaufman Brief Intelligence Test (K-BIT). Moderated multiple regression revealed a significant interaction effect. Crystallized ability (K-BIT vocabulary) was negatively related to psychoticism at low levels of fluid ability (K-BIT matrices) and positively related to psychoticism at high levels of fluid ability. These findings highlight the potential importance of psychoticism within GfGc investment theory.

MH/CHAOS: The CIA’s Campaign against the Radical New Left and the Black Panthers

Operation MHCHAOS was the code name for a secret domestic spying program conducted by the Central Intelligence Agency in the late 1960s and early 1970s charged with unmasking any foreign influences on left wing protestors. CIA counterintelligence officer Frank Rafalko was a part of that operation. When The New York Times revealed MHCHAOS in 1974 and Congress investigated, MHCHAOS took its place in the pantheon of intelligence abuses. However, in his new book Rafalko says that the operation was justified and that the CIA was the logical agency to conduct it. Listen as he defends his perspective with dramatic intelligence collected on the New Left and black radicals. This event took place on 26 October 2011.

India paper

The paper, Shared and Unique Components of Human Population Structure and Genome-Wide Signals of Positive Selection in South Asia, is free.

Summing up, our results confirm both ancestry and temporal complexity shaping the still on-going process of genetic structuring of South Asian populations. This intricacy cannot be readily explained by the putative recent influx of Indo-Aryans alone but suggests multiple gene flows to the South Asian gene pool, both from the west and east, over a much longer time span.

Dienekes: "I haven't read the paper fully yet (it's open access), but the abstract seems to agree with what I've written both here and over at the Dodecad blog, about South Asians being primarily a West Asian/South Asian variable mix." In fact, the authors note in the body of the paper:

Another example of an heuristic interpretation appears when we look at the two blue ancestry components (Figure 2B) that explain most of the genetic diversity observed in West Eurasian populations (at K = 8), we see that only the k4 dark blue component is present in India and northern Pakistani populations, whereas, in contrast, the k3 light blue component dominates in southern Pakistan and Iran. This patterning suggests additional complexity of gene flow between geographically adjacent populations because it would be difficult to explain the western ancestry component in Indian populations by simple and recent admixture from the Middle East.

Moreover:

Both PC2 and k5 light green at K = 8 extend from South Asia to Central Asia and the Caucasus (but not into eastern Europe). In an attempt to explore diversity gradients within this signal, we investigated the haplotypic diversity associated with the ancestry components revealed by ADMIXTURE. Our simulations show that one can detect differences in haplotype diversity for a migration event that occurred 500 generations ago, but chances to distinguish signals for older events will apparently decrease with increasing age because of recombination. In terms of human population history, our oldest simulated migration event occurred roughly 12,500 years ago and predates or coincides with the initial Neolithic expansion in the Near East. Knowing whether signals associated with the initial peopling of Eurasia fall within our detection limits requires additional extensive simulations, but our current results indicate that the often debated episode of South Asian prehistory, the putative Indo-Aryan migration 3,500 years ago (see e.g., Abdulla15) falls well within the limits of our haplotype-based approach. We found no regional diversity differences associated with k5 at K = 8. Thus, regardless of where this component was from (the Caucasus, Near East, Indus Valley, or Central Asia), its spread to other regions must have occurred well before our detection limits at 12,500 years. Accordingly, the introduction of k5 to South Asia cannot be explained by recent gene flow, such as the hypothetical Indo-Aryan migration.

First, note that the k5 "light green" ADMIXTURE component does in fact extend into and throughout Europe (apart from Sardinia). The authors believe they've shown "k5" must have "spread" well before the Neolithic. What they've actually demonstrated is that ADMIXTURE (at least as used here) will not be the tool to disentangle complex recent population movements in Eurasia.