race/history/evolution notes

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.

ESHG 2014: A mitogenomic phylogeny of haplogroups U2e and U3: revealing the phylogenetic signals for population expansions in the Slavs prehistory

Title: J17.66 - A mitogenomic phylogeny of haplogroups U2e and U3: revealing the phylogenetic signals for population expansions in the Slavs prehistory
Keywords: mitochondrial DNA; molecular phylogeography; molecular evolution
Authors: B. Malyarchuk1, M. Derenko1, T. Grzybowski2, M. Perkova1, G. Denisova1, A. Litvinov1, U. Rogalla2, K. Skonieczna2; 1Institute of Biological Problems of the North, Magadan, Russian Federation, 2Institute of Forensic Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland.

Abstract: To resolve the phylogeny of some uncommon and poorly studied West Eurasian mitochondrial DNA (mtDNA) haplogroups, we sequenced 32 U2e and 19 U3 complete mitogenomes of Central and Eastern Europeans (Czechs, Slovaks, Poles, Russians, Ukrainians and Belarusians) and re-analysed the available at the present time data on 74 U2e and 80 U3 complete mtDNAs. Molecular dating suggests that the coalescence time estimates are ~21 and ~35 thousand years (ky) for haplogroups U2e and U3, respectively. Detailed analysis of about 500 Slavic complete mitogenomes belonging to different haplogroups allowed us to identify a number of lineages that seem specific for Central and Eastern Europe (U3b1b, U4a2a1, U5a2a1c, U2e1b1a, U2e1b1, U3a1a, H5a1f, U5a1a1a1, U5a1c1, U2e2a1a, U4a2a, H5a2, U2e2a1d and U5a1b1b). These subhaplogroups consist of similar haplotypes revealed in different ethnic groups of modern Slavs, thereby proving the existence of ethnolinguistic community of Slavs through DNA testing. Evolutionary age of Slavic-specific subhaplogroups is calculated to approximately 3.9 ky (from 2.3 to 5.9 ky, according to the mutation rate proposed by Soares et al. (2009) for the entire mtDNA molecule). This indicates that the ancestors of modern Slavs inhabited areas of Central and Eastern Europe from the times of Bronze and Iron Ages, i.e. earlier than it was estimated on the basis of archaeological, historical and linguistic data. This study was supported by Russian Foundation for Basic Research (grant 14-04-00131) and the Program of Presidium of Russian Academy of Sciences (grant 12-I-P30-12).

ESHG 2014: Genetic landscape of populations along the Silk Road

Title: P17.64-M - Genetic landscape of populations along the Silk Road reveals a haplotype associated with hyposmia in Tajikistan's population
Keywords: olfactory receptor clusters; Silk Road; population structure
Authors: M. Mezzavilla1,2, S. Ulivi2, P. Gasparini1,2, V. Colonna3; 1University of Trieste, Trieste, Italy, 2Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”, Trieste, Italy, 3Institute of Genetics and Biophysics "A. Buzzati-Traverso", National Research Council (CNR), Napoli, Italy.

Abstract: Smell is a versatile mechanism for recognizing different odours and is mediated by olfactory receptors. While collecting phenotypes related to smell in six countries along the Silk Road, we found an increased rate of failure to discriminate odorants in individuals from Tajikistan respect to the other countries. Using haplotype-based association we linked this to a 15 kb region within olfactory receptor gene cluster on chromosome 6 (p-value 3.86e-05). This region is embedded in the largest intron of OR5V1 and is downstream OR11A1 and upstream OR12D3. We also analysed genetic variability in 1,114 unrelated samples either from the Silk Road and ten other worldwide populations at over 300,000 polymorphic sites and characterized population genetic structure of the Silk Road within a worldwide context with a resolution never obtained before. We identified genetic components peculiar to Central Asia and observed that Tajikistan behaves as an outlier population. Indeed Tajiks share a consistent number of unusually large stretches of homozygosity and have the lowest effective population size (Ne) among the studied populations, most likely as the result of past isolation and/or consanguinity. Altogether these novel findings clarify the complex genetic patterns of the Silk Road populations and suggest that the smell misperception phenotype observed in Tajikistan might be the result of a combination of genetic drift and relaxed selection at the olfactory receptors genes.

ESHG 2014: estimation of pairwise genetic correlations between hundreds of quantitative traits from population samples of thousands of individuals

Title: C11.3 - Efficient estimation of pairwise genetic correlations between hundreds of quantitative traits from population samples of thousands of individuals
Keywords: linear mixed model; genetic correlation
Authors: M. Pirinen1, C. Benner1, T. Lehtimäki2, J. G. Eriksson3,4,5, O. T. Raitakari6,7, M. Järvelin8,9,10, V. Salomaa3, S. Ripatti1,11,12; 1Institute for Molecular Medicine Finland, Helsinki, Finland, 2Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere School of Medicine, Tampere, Finland, 3Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, 4Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland, 5Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland, 6Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland, 7Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland, 8Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom, 9Institute of Health Sciences, University of Oulu, Oulu, Finland, 10Biocenter Oulu, University of Oulu, Oulu, Finland, 11Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom, 12Hjelt Institute, University of Helsinki, Helsinki, Finland.

Abstract: Several modern technologies, such as nuclear magnetic resonance and mass spectrometry platforms in metabolomics, produce high-dimensional phenotype data on individuals. A first step towards utilising high-dimensional phenotypes in genetic studies is to understand how their genetic components are related.

Recent algorithmic advances in multivariate linear mixed models have enabled variance component estimation for pairs of traits using population samples of individuals and genome-wide panels of SNPs. However, current methods have not been tailored for situations where hundreds of traits are available on the same set of individuals. For such settings, we introduce an algorithm that efficiently decomposes pairwise phenotypic correlations into genetic and environmental components.

We illustrate our approach with an application to 105 pairs of metabolic and anthropometric traits measured on up to 14,000 Finnish individuals. For example, we estimate that the observed phenotypic correlation (-0.41) between triglyserides (TG) and HDL cholesterol decomposes into an additive genetic correlation (-0.59, s.e. 0.06) and an environmental correlation (-0.36 s.e. 0.02).

We discuss the interpretation of genetic correlations as correlations between locus-wise genetic effects and characterise settings where prior information about genetic correlation increases statistical power to identify pleiotropic loci, i.e. loci that contribute to multiple traits.

ESHG 2014: some genetic associations for power vs. endurance athlete status

Title: J17.56 - The SHBG gene polymorphism (rs12150660) is associated with elite power athlete status and muscle mass
Keywords: SHBG; polymorphism; athletes
Authors: E. S. Egorova1, L. J. Mustafina2, I. I. Ahmetov2,1; 1Kazan State Medical University, Kazan, Russian Federation, 2Volga Region State Academy of Physical Culture, Sport and Tourism, Kazan, Russian Federation.

Abstract: Testosterone regulates muscle mass and strength, bone mass, fat distribution and the production of red blood cells. Sex hormone-binding globulin (SHBG) is the key protein responsible for binding and transporting of testosterone. SHBG regulates its bioavailability and therefore its effects in the body. Polymorphism at the SHBG gene locus (rs12150660 G/T) has been associated with testosterone concentrations. Since individuals with the TT genotype have higher serum testosterone concentrations in comparison with carriers of the G allele (data from GWAS), we hypothesized that the carriage of the T allele may give some advantage for strength and power performance. The aim of the study was to investigate the association between the SHBG G/T polymorphism, athlete status and muscle mass. A total of 363 Russian athletes and 130 controls were genotyped using RT-PCR. Muscle mass was measured by body composition analyzer Tanita MC-980. The frequencies of the T allele in power-oriented athletes (n=143, 20.3%; P=0.7462), endurance-oriented athletes (n=220, 15.0%; P=0.2054) and a whole cohort of athletes (17.1%; P=0.5078) were not significantly different from controls (18.8%). However, the frequency of the T allele in elite power-oriented athletes (n=65, 26.2 vs. 12%, P=0.0061) was significantly higher as compared with elite endurance-oriented athletes (n=58). Furthermore, correlation analysis showed positive association between the T allele and muscle mass among non-elite female athletes (n=8, P=0.0072, r= 0.8729). Although more evidence is needed, one might suggest that the SHBG gene G/T polymorphism is associated with power athlete status.

Title: J17.28 - Genome-wide association analysis identifies a locus on DMD (dystrophin) gene for power athlete status in Russians
Keywords: GWAS; athlete; DMD
Authors: V. A. Naumov1, I. I. Ahmetov2, A. K. Larin1, E. V. Generozov1, N. A. Kulemin1, E. A. Ospanova1, A. V. Pavlenko1, E. S. Kostryukova1, D. G. Alexeev1, V. M. Govorun1; 1Research Institute for Physical-Chemical Medicine, Moscow, Russian Federation, 2Volga Region State Academy of Physical Culture, Sport and Tourism, Kazan, Russian Federation.

Abstract: Power athlete status is a heritable trait: around two-thirds of the variance in this phenotype is explained by genetic factors. Since power and endurance are located at the opposite extremes of a muscle performance continuum, a genome-wide association study (GWAS) of elite Russian power-oriented athletes (sprinters and strength athletes) and endurance-oriented athletes as controls was performed to identify common genetic variants associated with elite power athlete status. 102 sprinters, 86 strength athletes and 178 endurance-oriented athletes were genotyped using the Illumina® HumanOmni1-Quad BeadChips. When comparing sprinters and endurance-oriented athletes, the most significant association (P=6.2[[unable to display character: ∗]]10-7) was shown for the rs939787 polymorphism. Interestingly, this association was replicated (P=2.9[[unable to display character: ∗]]10-6) by comparing strength athletes and endurance-oriented athletes (P=3[[unable to display character: ∗]]10-8 when sprinters and strength athletes were combined). The rs939787 is located in the DMD (dystrophin) gene which plays an important role in muscle contraction and strength, linking the intracellular cytoskeleton to the extracellular matrix. In conclusion, our data suggest that the DMD gene rs939787 polymorphism is associated with elite power athlete status in Russians.

Title: J17.58 - Variations in nuclear genes are associated with elite sport performance in the Polish population
Keywords: sport performance; ACE; ACTN3
Authors: B. J. Peplonska1, K. Safranow2, J. G. Adamczyk3, M. Siewierski3, H. Sozański3, A. K. Gajewski3, M. Berdynski1, A. Maruszak1, C. Zekanowski3; 1Mossakowski Medical Research Centre Polish Academy of Sciences, Warszawa, Poland, 2Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland, 3Department of Sport’s Theory, Institute of Sport, Jozef Pilsudski University oh Physical Education in Warsaw, Warszawa, Poland.

Abstract: Objectives: Single nucleotide polymorphisms are the most common type of human genetic variation. It is widely recognized that genetic factors located in mitochondrial and nuclear genomes influence sport performance. The aim of our study was to assess whether selected nuclear DNA variants are associated with athlete performance in the Polish population.

Methods: The study group comprised 413 unrelated elite athletes and the control group consisted of 451unrelated sedentary individuals. The athletes were stratified into two subgroups: the power athletes (n=188) and the endurance ones (n=225). The study group included 284 participants of Olympic and International Games and the remaining 129 athletes were national[[unable to display character: –]]level athletes. The DNA was isolated from peripheral blood lymphocytes using standard procedures. Genotyping of 10 nuclear DNA variants (ACE, rs4341; ACTN3, rs1815739; GABPB1, rs12594956; CHRNB3, rs4950; AGT, rs699; FAAH, rs324420; PPARG, rs1801282; TFAM, rs1937; TFAM, rs 2306604; PGC1α, rs 8192678) was conducted using TaqMan method. All statistical analyses were performed using Statistica ver. 10.

Results: We showed that six polymorphisms were associated with outstanding results in power (TFAM,rs 2306604, FAAH, ACE, ACTN3) or endurance sports (CHRNB3, GABP1). Gender and sport level of athletes were also significant

Conclusion: Our study indicates that in the Polish population genetic background could influence sport performance.

Title: J17.48 - The association of REN gene polymorphism with athlete status and muscle mass
Keywords: polymorphism; REN gene; skeletal muscle
Authors: L. J. Mustafina1,2, G. N. Khafizova1, R. R. Almetova1, R. R. Kasimova1, E. S. Egorova2, I. I. Ahmetov1,2; 1Volga Region State Academy of Physical Culture, Sport and Tourism, Kazan, Russian Federation, 2Kazan State Medical University, Kazan, Russian Federation.

Abstract: The renin-angiotensin system (RAS) is supposed to be one of the regulators of skeletal muscle growth and differentiation (Zhang et al. 2003; Johnston et al. 2011). Renin (encoded by REN gene), as a component of the RAS, activates the renin-angiotensin cascade by catalyzing the conversion of angiotensinogen to angiotensin I (Rupert, 2006). The aim of present study was to investigate the association between the intron 8 83A/G (rs2368564) polymorphism of the REN gene, athlete status and muscle mass in Russians. Two hundred and sixty eight Russian athletes (90 females and 178 males) from different sporting disciplines were involved in the study. REN genotype and allele frequencies were compared to 151 controls (74 females and 77 males). Genotyping for the REN polymorphism was performed by RT-PCR. Muscle mass parameters were assessed by bioelectrical impedance analyzer Tanita MC 980 (Japan) in 125 athletes (44 females and 81 males). We found that the frequency of the REN G allele was significantly higher in power-oriented athletes (78 vs 68%; P=0.021) compared to controls and this difference was even more pronounced in elite power-oriented athletes (89%; P=0.018). Furthermore, the REN G allele was positively correlated with fat-free mass, absolute muscle mass, muscle mass of trunk and left/right legs in elite athletes. In conclusion, we have shown that the 83A/G polymorphism of the REN gene is associated with power athlete status and skeletal muscle parameters in Russians.

ESHG 2014: Genomic description of the Generation Scotland Cohort: a large family base genetic study

Title: P17.29-S - Genomic description of the Generation Scotland Cohort: a large family base genetic study
Keywords: Genetic introgression; Principal Component Analysis; GS:SFHS
Authors: C. Amador1, J. Huffman1, H. Trochet1, A. Campbell1, D. Porteous1, G. Scotland1, N. Hastie1, V. Vitart1, C. Hayward1, P. Navarro1, C. S. Haley1,2; 1MRC IGMM, University of Edinburgh, Edinburgh, United Kingdom, 2Roslin Institute and Royal (Dick) School of Veterinary Studies, Edinburgh, United Kingdom.

Abstract: Generation Scotland’s Scottish Family Health Study (GS:SFHS) includes over 24,000 participants from across Scotland with records for health-related traits and environmental covariates, 10,000 genotyped for ~700K SNPs. The cohort represents an important resource for the study of complex traits and diseases. We have analysed the genomic structure of GS:SFHS as a preliminary step towards choosing appropriate subsets of individuals and statistical techniques for future studies. Initially we merged the GS:SFHS data with 1092 individuals of diverse ancestries from the 1000 Genomes project and estimated genomic relationships using the ~700K SNPs. A Principal Component Analysis on the resulting relationships facilitated identification of a group of 70 individuals of likely Italian ancestry and a number of individuals with African or Asian ancestry. We characterised the amount of genetic introgression and were able to differentiate between individuals with a few small exogenous regions in their genome, and those with long exogenous haplotypes covering a large part of the genome. We found that the pattern of homozygosity was very similar to that of other European populations and identified an individual carrying a chromosome 1 uniparental disomy. Overall, there is very limited evidence for geographic differentiation or stratification of the GS:SFHS sample within Scotland. These findings provide a genomic perspective on the history of the Scottish population, and have implications for further analyses, such as studying the contributions of common and rare variants to trait heritabilities and evaluation of genomic and phenotypic prediction of disease.

ESHG 2014: The influence of genetics on personality development

Title: P16.66-M - The influence of genetics on personality development
Keywords: Personality; NEO-FFI Authors: K. B. Wolffhechel1, H. Jarmer1, S. M. van den Berg2, M. H. M. de Moor3, D. I. Boomsma3; 1Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark, 2Department of Research Methodology, Measurement and Data Analysis, University of Twente, Enschede, Netherlands, 3Department of Biological Psychology, VU University Amsterdam, Amsterdam, Netherlands.

Abstract: Personality is known as hereditary to a certain extent. In this work we attempt to classify personality traits as binary traits based on genetic information only. For this we used the 60-item NEO-FFI and over 8 million SNPs from 6655 Dutch participants. For feature selection we performed a genome-wide association for each personality trait in a five-fold cross validation setup. All SNPs with a p-value < 0.01 were chosen as predictors for a given fold and a given personality trait, amounting to approximately 2,500 associated SNPs for each trait. An artificial neural network was trained with the SNPs as input and the personality scores as output. We found it possible to classify a person’s personality to the two sides of the scale significantly better than random. The results of this study prove in a novel way that genetics have an influence on personality. The next step is to identify, which genes these SNPs belong to, which hopefully will lead to a greater understanding of the processes involved in personality development and the onset of personality disorders.

ESHG 2014: Multiple genes of small effect and their interactions with environmental factors explain variation in personality traits

Title: J14.29 - Multiple genes of small effect and their interactions with environmental factors explain variation in personality traits Keywords: personality traits; brain derived neurotrophic factor; GxE model Authors: A. Kazantseva1, Y. Kutlumbetova2, S. Malykh3, R. Kanzafarova2, T. Traks4, S. Koks5, M. Lobaskova6, E. Khusnutdinova1,2; 1Institute of Biochemistry and Genetics Ufa Scientific Center of Russian Academy of Sciencies, Ufa, Russian Federation, 2Bashkir State University, Ufa, Russian Federation, 3Psychological Institute, Russian Academy of Education, Moscow, Russian Federation, 4Department of Physiology, University of Tartu, Tartu, Estonia, 5Department of Pathophysiology, University of Tartu, Tartu, Estonia, 6Udmurt State University, Izhevsk, Russian Federation.

Abstract: Personality traits are thought to be endophenotypes (high Harm Avoidance (HA), low Self-directedness (SD)) for most psychiatric disorders and predictors of life outcomes. Genetic influences on personality traits are attributable to many genes of small effect and are modulated by environmental factors. We aimed to examine gene-environment (GxE) and gene-gene (GxG) interaction models based on neurotrophic factor (NGF, BDNF, NTRK2, NTRK3), serotoninergic (SLC6A4, TPH1) and dopaminergic system (DRD2, SLC6A3) gene polymorphisms contributing into personality traits variation in healthy individuals.

In total, 1018 healthy individuals (68% women) from Russia (mean age±SD: 19.81±2.65 years) without any history of psychopathologies were subjected to personality traits assessment via TCI-125 (Cloninger et al., 1993). Involved individuals are Caucasians from Russian (N=409), Tatar (N=290), Bashkir (N=130) and Udmurt populations (N=189). Socio-demographic data including gender, ethnicity, order and season of birth (SOB), place of residence, level of income, childhood maltreatment were obtained. Genotyping of 70 SNPs was performed with SNPlexTM platform (Applied Biosystems). Statistical analysis was conducted with PLINK v.1.07 corrected via FDR-procedure for multiple comparisons.

The present study revealed GxE models demonstrated BDNF Val66Met*SOB (PFDR=0.036), BDNF rs1519479*ethnicity (PFDR=0.042) and 5-HTTLPR*SOB (PFDR=0.05) interactions affected HA. Moreover, variations in SD were caused by interactions between BDNF Val66Met (PFDR=0.048), BDNF rs2030323 (PFDR=0.035) and ethnicity. Accordingly, genetic testing for BDNF and 5-HTT gene polymorphisms assuming gender, ethnicity and SOB confounding is necessary for psychopathologies prevention at early stages. This work was supported by Russian foundation for humanities grant 13-06-00583a.

ESHG 2014: A genome-wide association study of Agreeableness suggests a novel association in the NAV2 gene in Korean women

Title: P17.66-M - A genome-wide association study of Agreeableness suggests a novel association in the NAV2 gene in Korean women
Keywords: Personality; GWAS; Agreeableness
Authors: H. Kim1, S. Roh1, B. Kim1, H. Kim1, H. Cho1, N. Cho2, C. Shin3, J. Sung4, H. Kim1; 1Ewha Womans University, Seoul, Korea, Republic of, 2Ajou University, Seoul, Korea, Republic of, 3Korea University, Seoul, Korea, Republic of, 4Seoul National University, Seoul, Korea, Republic of.

Abstract: Data from genome-wide association (GWA) studies have been used to find the common variants of personality. In a previous study, we reported that neurotransmitters and the olfactory receptor 1A2 gene are associated with neuroticism in a cohort of young Korean women. However, many genetic variants that are highly associated with certain personality traits are still unknown. Here, we report on a meta-analysis of GWA data for personality in three cohorts samples (2045 individuals). All participants were of Korean ancestry. Personality traits were measured with the Revised Neuroticism-Extraversion-Openness Personality Inventory to assess five factors: Neuroticism, Extraversion, Agreeableness, Openness, and Conscientiousness. In either discovery stage, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. We observed consistent direction of effect and significant association of the NAV2 gene and Agreeableness in either the discovery and combined stage (p=7.85×10-7, for meta-analysis). NAV2 gene involves in optic nerve development and sensory perception of smell and sound. We previously reported that the sensory system may play an important role in personality, and the present study leads to the same conclusion. The sensory system affects personality as a filter of the acceptance system, which may have an advantage to reconstruction. This study was supported by a grant of the National Project for Personalized Genomic Medicine, Ministry for Health & Welfare, Republic of Korea (A111218).

ESHG 2014: Genome wide inbreeding estimation within Lebanese communities using SNP arrays

Title: P17.74-M - Genome wide inbreeding estimation within Lebanese communities using SNP arrays
Keywords: Remote consanguinity; Homozygous by descent; Inbreeding coefficient
Authors: N. Jalkh1,2, M. Sahbatou3, E. Chouery1, A. Megarbane1, A. Leutennegger4,5, J. Serre2; 1Unité de Génétique Médicale et Laboratoire associé INSERM à l’Unité UMR_S910, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon, 2EA 2493 « pathologie cellulaire & génétique, de la conception à la naissance », Université de Versailles-Saint Quentin en Yvelines, Paris, France, 3Fondation Jean Dausset-CEPH, Paris, France, 4Université Paris Diderot, Institut Universitaire d’Hématologie, UMR-S946, Paris, France, 5Inserm, U946, F-75010, Paris, France.

Abstract: Consanguineous marriages have been widely practiced, with variable rates, in several global communities depending on religion, culture, and geography. The populations of the Middle East are among those with the highest inbreeding level and frequency of inbred individuals. A genome wide analyses of 165 unrelated Lebanese has been performed either through the estimation of LOH (Loss of Heterozygosity) or through the FEstim algorithm depending on SNP frequencies. Relying on these genome-wide data that identify regions of homozygosity by descent (HBD), this study was able to estimate total inbreeding levels, remote consanguinity, and population admixture and structure. The inbreeding coefficient value was estimated to be 1.6% in offspring of unrelated parents (over 3 generations) and 8% in offspring of first cousins. In either case, the remote consanguinity (RC) value was approximately equal to 0.6% resulting from genetic drift or recurrent consanguineous unions. This RC value suggests that for any unrelated marriages in Lebanon, the mates could be related as third cousins or as second cousins once removed. Under the hypothesis that 25% of marriages occur between first cousins, the mean inbreeding (F) value of 2.2% found may explain the increased incidence of recessive disease within offspring. The LOH and FEstim genome wide approaches were applied to investigate the genomic similarity of Lebanese communities. Both approaches revealed a unique ancestral population of the four studied communities (Greek Orthodox, Maronite, Shiite and Sunni).

ESHG 2014: The role of population isolates in understanding genetic and complex diseases

Title: S08.3 - The role of population isolates in understanding genetic and complex diseases
Keywords: genetic isolates; complex and quantitative traits; genetic diseases
Authors: P. Gasparini; Trieste, Italy.

Abstract: The use of isolated populations to reduce disease heterogeneity of complex disorders has already proven very useful in identifying DNA polymorphisms associated with complex diseases and quantitative traits. The study of complex traits in geographically and culturally isolated populations is particularly useful because the entire population can be analyzed, the relative weight of environmental variation can be controlled and genetic factors can be more easily identified. In these genetically and culturally homogeneous populations, a large proportion of individuals presenting a given trait is likely to share the same trait-predisposing gene inherited from a common ancestor. Furthermore, inbreeding, typical of small communities, reduces genetic heterogeneity and increases homozygosity, providing greater power for detection of susceptibility genes. We have created the Italian Network of Genetic Isolates (INGI) that collects the samples coming from several villages from 5 different Italian regions for a total of more than 6000 samples. Moreover, additional 1500 samples have been collected along the Silk Road. For all of them a great number of information regarding medical records, hematological parameters and lifestyle has been collected as well as DNA samples which have been genotyped with high density chip arrays. To evaluate the power to detect association in our cohorts we aimed at replicating several already published results and to verify if any new Italian specific loci were present. For example, GWAS were carried out on several hematological and serum lipids traits, blood glucose levels, blood pressure and anthropometric measures leading to the replication of 206 loci and to the discovery of some novel associations for BMI and weight. For 12 of these loci the top associated SNP was different from the one previously published highlighting the importance of having a population specific reference panel for personalized medicine. Moreover, specific genes/variants associated to phenotypes such as hearing, smell, taste and food preferences have been identified. More recently, new data have been obtained using whole genome sequencing data that allow refining the results previously obtained and will lead to the discovery of even more population specific genetic variants. Our results show that genetic isolates are a powerful resource for studying complex traits and thus to create genetic risk profiles which will be the bases for personalized medicine in Italy. Updated data will be presented and discussed.

ESHG 2014: Y chromosome haplogroups C, N and Q in Eurasian populations for the perspectives of proto-Bulgarian ancestry

Title: P17.92-M - Meta-analysis of Y chromosome haplogroups C, N and Q in Eurasian populations for the perspectives of proto-Bulgarian ancestry
Keywords: Y-chromosome; haplogroup; proto-Bulgarians
Authors: S. Karachanak1, D. Nesheva1, V. Grugni2, N. Al-Zahery2, V. Battaglia,2, A. S. Galabov3, D. Toncheva1; 1Department of Medical Genetics, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria, 2Department of Biology and Biotechnologies “Lazzaro Spallanzani”. University of Pavia, Pavia, Italy, 3The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.

Abstract: Bulgaria is situated on the presumed trajectory of the pioneer colonization of Europe. Since then it has been subjected to a series of demographic events with disputable impact on the contemporary Bulgarian gene pool. One of the most controversial issues of the Bulgarian past is the origin of the proto-Bulgarians, which were previously considered as a sparse Turkic population.

In order to delve into Bulgarian patrilineal origins we have performed a survey of Y-chromosome haplogroups followed by meta-analysis of haplogroups C, N and Q distinctive for Altaic populations. The analysis was performed on a sample comprising 808 Bulgarian males using RFLP and DHPLC analysis. We have found that only 1.49 % of the contemporary gene pool belongs to haplogroups C, N and Q. Our results were used to upgrade and extend the distribution maps of these haplogroups and to compare their frequency in 240 Eurasian (sub-) populations with more than 20 000 samples.

The comparison reveals a statistically significant difference in the distribution of the studied haplogroups between Bulgarians and Altaic populations as well as between Bulgarians and Eastern Slavic populations. Based on the novel historical studies which point to a substantial contribution of the proto-Bulgarians to the modern Bulgarian gene pool the obtained results suggest that there is no common genetic ancestry between proto-Bulgarians and present day Altaic populations as they reject the hypothesis of the Turkic origin of proto-Bulgarians.

ESHG 2014: Y-chromosome Polymorphisms in Kazakh Populations from the Perspective of Tribal-clan structure

Title: J17.65 - Characteristics of Y-chromosome Polymorphisms in Kazakh Populations from the Perspective of Tribal-clan structure
Keywords: Y-chromosome Polymorphisms; Kazakh Populations; Tribal-clan structure
Authors: M. Zhabagin1,2, Z. Sabitov3, H. Dibirova4, E. Balanovska4, I. Zakharov2, O. Balanovsky2; 1Center for Life Sciences, Nazarbayev University, Astana, Kazakhstan, 2Vavilov Institute of General Genetics RAS, Moscow, Russian Federation, 3Gumilyov Eurasian National University, Astana, Kazakhstan, 4Research Centre of Medical Genetics RAMS, Moscow, Russian Federation.

Abstract: The characteristic feature of the Kazakh nomadic society was the presence of a hierarchically organized and widely branched tribal-clan structure called “Shezhire”, which reflected complex system of ethno-social organization. In the context of the Shezhire, Kazakh populations are divided into three ethno-territorial association of tribes called "Zhuz" (Great, Middle, and Small Zhuzes) and a group of aristocratic tribes (Tore, Kozha, Sunak).

This study aims to compare Y-chromosomal polymorphism of three Kazakh Zhuzs and group of aristocratic tribes (total sample size N= 1407). We analyzed 40 SNP and 17 STR Y-chromosomal markers. Summary statistics were calculated using Arlequin 3.5. Neighbor-joining tree was constructed by the program MEGA 5.0. Multidimensional scaling plot was drawn by the software package Statistica v.7.1.

Population pairwise FST values were calculated from the Y-chromosomal haplogroup frequencies to assess the genetic similarity among studied groups of Kazakh tribes. The most distant ones were the tribe of Sunak and the Small Zhuz (0.393), whereas the shortest distance was found between the tribe of Tore and the Great Zhuz (0,021). These genetic distances are associated with the geographic distances between studied populations. The distribution of Y-chromosomal haplogroups is strongly correlated with the tribal-clan structure of Kazakhs. Presence of certain haplogroups at high frequency at particular tribes is in favor to the hypothesis that many tribes go back to one biological founder, confirming the link between Kazakh family tree Shezhire with the genetic composition.

A Genetic Census of America

More complete AncestryDNA estimates of genetic ancestry by state (interactive maps at link):

Using AncestryDNA results from over a quarter million people, the AncestryDNA science team set out to perform a “genetic census” of the United States. [. . .]
Solely using ethnicity estimated by DNA, these maps reveal spatial patterns that are telling of the ancestral origins of present day Americans: where they came from and where they eventually settled. [. . .]
SCANDINAVIAN ETHNICITY
For example, let’s look at the Scandinavian map. Scandinavian immigrants – from Sweden, Norway, and Denmark – tended to settle in the upper Midwest where geography, culture, and local economics felt familiar to life in the old country.
On the map, these are the greenest regions: the states with the highest amounts of Scandinavian ancestry. In other words, DNA also suggests localized migration of individuals of Scandinavian origin to North Dakota, Minnesota, and neighboring states, with little migration to other U.S. regions. History agrees with genetics!
IRISH ETHNICITY
Look at the Irish ancestry map as another example. The highest statewide averages are concentrated in Massachusetts and other states in the Northeastern U.S. – where many Irish immigrants, forced to leave their homes and lands, settled in the 19th century. Growing numbers of Irish that arrived after the 1820s were often poor and common laborers, and took jobs in the construction of buildings, canals, roads, and railways in cities in the eastern United States.
Many of these cities still show the highest average amounts of Irish ethnicity in the U.S. today! DNA affirms that many descendants of Irish immigrants still live where their ancestors initially settled – in the Northeast.
GREAT BRITAIN AND WESTERN EUROPE ETHNICITY
If you look at the maps for Great Britain and Europe West, you see that other ancestries are more widespread across the whole country. Leading up to the Boston Tea Party and the Declaration of Independence in 1776, large numbers of Europeans arrived in what is now the U.S., in some cases to escape religious persecution. While there were subsequently many waves of immigration, individuals primarily from Western Europe and Great Britain were our first Americans.
That we see British ancestry in many people of the U.S. may be evidence of the long history of individuals from Great Britain migrating to the United States, and far and wide across those states.

As I mentioned, the "Irish" estimates are likely inflated in much of the country, with Scotch-Irish, Scottish, and Welsh probably contributing a considerable part of the "Irish" component outside of the Northeast.

Genetic estimate of percent Irish ancestry in US

'Based on AncestryDNA ethnicity estimates for over 300,000 AncestryDNA customers*, the AncestryDNA science team set out to discover the “most Irish” regions of the U.S.':

States with the highest Irish ancestry
First, for all AncestryDNA ethnicity estimates of people born in the same state, we averaged their fractions of Irish ethnicity. Then, we found the U.S. states whose residents have the highest, and lowest, amounts of Irish ancestry.
On the map are the top five states with the highest average Irish ancestry. Massachusetts is #1, and all of the other top states are also in the Northeast.

AncestryDNA estimates its Massachusetts-born customers average 28.5% Irish genetically, which is reasonably close to my surname-based estimate of 26% (using 1940 census data).

AncestryDNA's estimates of Irish ancestry for much of the rest of the country are likely inflated, however. AncestryDNA's "Irish" cluster spills over into Scotland and Wales, and to a lesser extent even into England and France. While (in an analysis shown in the AncestryDNA white paper) 95% of Irish are placed into the "Irish" cluster, only something like 60% of British are placed into the "Great Britain" cluster (with most of the rest presumably being placed into either the "Irish" or "Europe West" clusters). AncestryDNA's estimates rely on ADMIXTURE, an allele frequency-based approach, whereas I think very large data sets and an approach that makes use of haplotype information will be needed to clearly dissect recent ancestry within Northwestern Europe.

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.

Genetic genealogy talks

Some DNA lectures from Who Do You Think You Are 2014:

Scottish DNA - Clans, Families, and Surnames (Alasdair Macdonald)

Wales, DNA & Surnames (Brian Swann)

Autosomal DNA Success Stories (Emily Aulicino, Maurice Gleeson, Katherine Borges)

The Basics of DNA Testing (Katherine Borges)

Autosomal DNA - a step-by-step approach to analysing your atDNA matches (Maurice Gleeson)

DNA for Beginners - the three tests (Debbie Kennett)

Update: A few more have been posted.

Citizen Science - an online community approach to researching haplogroup R1b1a2 (Andy Grierson)

Men, Metal, and the Recent Re-Peopling of Western Europe (Michael Hammer)

Combining Traditional & Genetic Genealogy - The Pomeroy DNA Project (Chris Pomery)

Heritability of facial attractiveness and masculinity-femininity

Estimating the Sex-Specific Effects of Genes on Facial Attractiveness and Sexual Dimorphism (pdf)

Human facial attractiveness and facial sexual dimorphism (masculinity–femininity) are important facets of mate choice and are hypothesized to honestly advertise genetic quality. However, it is unclear whether genes influencing facial attractiveness and masculinity–femininity have similar, opposing, or independent effects across sex, and the heritability of these phenotypes is poorly characterized. To investigate these issues, we assessed facial attractiveness and facial masculinity–femininity in the largest genetically informative sample (n = 1,580 same- and opposite-sex twin pairs and siblings) to assess these questions to date. The heritability was ~0.50–0.70 for attractiveness and ~0.40–0.50 for facial masculinity–femininity, indicating that, despite ostensible selection on genes influencing these traits, substantial genetic variation persists in both. Importantly, we found evidence for intralocus sexual conflict, whereby alleles that increase masculinity in males have the same effect in females. Additionally, genetic influences on attractiveness were shared across the sexes, suggesting that attractive fathers tend to have attractive daughters and attractive mothers tend to have attractive sons.