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
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.
