Investigating the genetic architecture of eye colour in a Canadian cohort

Frida Lona-Durazo; Rohit Thakur; Erola Pairo-Castineira; Karen Funderburk; Tongwu Zhang; Michael A. Kovacs; Jiyeon Choi; Ian J. Jackson; Kevin M. Brown; Esteban J. Parra

iScience (Jun 2022)

Investigating the genetic architecture of eye colour in a Canadian cohort

Frida Lona-Durazo,
Rohit Thakur,
Erola Pairo-Castineira,
Karen Funderburk,
Tongwu Zhang,
Michael A. Kovacs,
Jiyeon Choi,
Ian J. Jackson,
Kevin M. Brown,
Esteban J. Parra

Affiliations

Frida Lona-Durazo: Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada; Corresponding author
Rohit Thakur: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Erola Pairo-Castineira: MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, UK; Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, UK
Karen Funderburk: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Tongwu Zhang: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Michael A. Kovacs: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Jiyeon Choi: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Ian J. Jackson: MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, UK
Kevin M. Brown: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Esteban J. Parra: Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada; Corresponding author

Journal volume & issue: Vol. 25, no. 6
p. 104485

Abstract

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Summary: Eye color is highly variable in populations with European ancestry, ranging from low to high quantities of melanin in the iris. Polymorphisms in the HERC2/OCA2 locus have the largest effect on eye color in these populations, although other genomic regions also influence eye color. We performed genome-wide association studies of eye color in a Canadian cohort of European ancestry (N = 5,641) and investigated candidate causal variants. We uncovered several candidate causal signals in the HERC2/OCA2 region, whereas other loci likely harbor a single causal signal. We observed colocalization of eye color signals with the expression or methylation profiles of cultured primary melanocytes. Genetic correlations of eye and hair color suggest high genome-wide pleiotropy, but locus-level differences in the genetic architecture of both traits. Overall, we provide a better picture of the polymorphisms underpinning eye color variation, which may be a consequence of specific molecular processes in the iris melanocytes.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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