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Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color.

ABSTRACT: Human eye color is highly heritable, but its genetic architecture is not yet fully understood. We report the results of the largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations. We identify 124 independent associations arising from 61 discrete genomic regions, including 50 previously unidentified. We find evidence for genes involved in melanin pigmentation, but we also find associations with genes involved in iris morphology and structure. Further analyses in 1636 Asian participants from two populations suggest that iris pigmentation variation in Asians is genetically similar to Europeans, albeit with smaller effect sizes. Our findings collectively explain 53.2% (95% confidence interval, 45.4 to 61.0%) of eye color variation using common single-nucleotide polymorphisms. Overall, our study outcomes demonstrate that the genetic complexity of human eye color considerably exceeds previous knowledge and expectations, highlighting eye color as a genetically highly complex human trait.

SUBMITTER: Simcoe M

PROVIDER: S-EPMC7946369 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color.

Simcoe Mark M Valdes Ana A Liu Fan F Furlotte Nicholas A NA Evans David M DM Hemani Gibran G Ring Susan M SM Smith George Davey GD Duffy David L DL Zhu Gu G Gordon Scott D SD Medland Sarah E SE Vuckovic Dragana D Girotto Giorgia G Sala Cinzia C Catamo Eulalia E Concas Maria Pina MP Brumat Marco M Gasparini Paolo P Toniolo Daniela D Cocca Massimiliano M Robino Antonietta A Yazar Seyhan S Hewitt Alex A Wu Wenting W Kraft Peter P Hammond Christopher J CJ Shi Yuan Y Chen Yan Y Zeng Changqing C Klaver Caroline C W CCW Uitterlinden Andre G AG Ikram M Arfan MA Hamer Merel A MA van Duijn Cornelia M CM Nijsten Tamar T Han Jiali J Mackey David A DA Martin Nicholas G NG Cheng Ching-Yu CY Hinds David A DA Spector Timothy D TD Kayser Manfred M Hysi Pirro G PG

Science advances 20210310 11

Human eye color is highly heritable, but its genetic architecture is not yet fully understood. We report the results of the largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations. We identify 124 independent associations arising from 61 discrete genomic regions, including 50 previously unidentified. We find evidence for genes involved in melanin pigmentation, but we also find associations with genes involved in iris morpholo ...[more]

PMID: 33692100

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Project description:Neuroticism is a personality trait of fundamental importance for psychological well-being and public health. It is strongly associated with major depressive disorder (MDD) and several other psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes. Here we report a combined meta-analysis of genome-wide association study (GWAS) of neuroticism that includes 91 370 participants from the UK Biobank cohort, 6659 participants from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and 8687 participants from a QIMR (Queensland Institute of Medical Research) Berghofer Medical Research Institute (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Form's Neuroticism scale. We found a single-nucleotide polymorphism-based heritability estimate for neuroticism of ∼15% (s.e.=0.7%). Meta-analysis identified nine novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (P=1.5 × 10(-15)) spanning 4 Mb and containing at least 36 genes. Other associated loci included interesting candidate genes on chromosome 1 (GRIK3 (glutamate receptor ionotropic kainate 3)), chromosome 4 (KLHL2 (Kelch-like protein 2)), chromosome 17 (CRHR1 (corticotropin-releasing hormone receptor 1) and MAPT (microtubule-associated protein Tau)) and on chromosome 18 (CELF4 (CUGBP elav-like family member 4)). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a strong genetic correlation between neuroticism and MDD and a less strong but significant genetic correlation with schizophrenia, although not with bipolar disorder. Polygenic risk scores derived from the primary UK Biobank sample captured ∼1% of the variance in neuroticism in the GS:SFHS and QIMR samples, although most of the genome-wide significant alleles identified within a UK Biobank-only GWAS of neuroticism were not independently replicated within these cohorts. The identification of nine novel neuroticism-associated loci will drive forward future work on the neurobiology of neuroticism and related phenotypes.

Dataset Information

Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color.

Publications

Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color.

Similar Datasets

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