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

doi:10.1016/j.isci.2022.104485

Investigating the genetic architecture of eye colour in a Canadian cohort

iScience. 2022 May 30;25(6):104485. doi: 10.1016/j.isci.2022.104485. eCollection 2022 Jun 17.

Authors

Frida Lona-Durazo¹, Rohit Thakur^{2

3}, Erola Pairo-Castineira^{4

5}, Karen Funderburk², Tongwu Zhang^{2

3}, Michael A Kovacs², Jiyeon Choi², Ian J Jackson⁴, Kevin M Brown², Esteban J Parra¹

Affiliations

¹ Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada.
² Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
³ Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁴ MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, UK.
⁵ Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, UK.

Abstract

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.

Keywords: Genetics; Genomics; Human Genetics.