Rare variant analyses across multiethnic cohorts identify novel genes for refractive error.


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Authors
Musolf, Anthony M 
Haarman, Annechien EG  ORCID logo  https://orcid.org/0000-0002-1452-5700
Luben, Robert N 
Patasova, Karina 
Abstract

Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests of mean Spherical Equivalent with rare variants in exome array data from the Consortium for Refractive Error and Myopia (CREAM). The dataset consisted of over 27,000 total subjects from five cohorts of Indo-European and Eastern Asian ethnicity. We identified 129 unique genes associated with refractive error, many of which were replicated in multiple cohorts. Our best novel candidates included the retina expressed PDCD6IP, the circadian rhythm gene PER3, and P4HTM, which affects eye morphology. Future work will include functional studies and validation. Identification of genes contributing to refractive error and future understanding of their function may lead to better treatment and prevention of refractive errors, which themselves are important risk factors for various blinding conditions.

Description

Funder: U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)


Funder: U.S. Department of Health & Human Services | National Institutes of Health (NIH)


Funder: Intraamural Research Program, National Human Genome Research Institute, National Institutes of Health

Keywords
Article, /631/208/205/2138, /631/208/729/743, /631/208/480, /631/114/2407, /631/208/727/2000, /45/43, article
Journal Title
Commun Biol
Conference Name
Journal ISSN
2399-3642
2399-3642
Volume Title
Publisher
Springer Science and Business Media LLC
Sponsorship
U.S. Department of Health & Human Services | National Institutes of Health (NIH) (R01-GM129325, 5R01 DK07 57 87 -13, under subward-agreement GENFDOOO1B52751)
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) (648268))
Netherlands Organisation for Scientific Research | Nationaal Regieorgaan Praktijkgericht Onderzoek SIA (Nationaal Regieorgaan Praktijkgericht Onderzoek) (91815655)
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research) (91617076, 050-060-810)
U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) (R01EY020483, EY06594, R01EY021531, 1RO1EY018246)
Department of Health | National Health and Medical Research Council (NHMRC) (MC_UU_00007/10, 1 021 105, 1 121 979 and 1 126 494)
Hrvatska Zaklada za Znanost (Croatian Science Foundation) (8875)
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Euratom (H2020 Euratom Research and Training Programme 2014-2018) (692145, 633589, 654248)
Eesti Teadusagentuur (Estonian Research Council) (IUT20-60, (PRG687)
EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj) (5R01 DK07 57 87 -13, under subward-agreement GENFDOOO1B52751)
RCUK | Medical Research Council (MRC) (MR/N003284/1 and MC-UU_12015/1), MC_PC_13048)
Cancer Research UK (CRUK) (C864/A14136)
Academy of Finland (Suomen Akatemia) (213506, 129680)
MOH | National Medical Research Council (NMRC) (NMRC 0796/2003, NMRC 1176/2008, STaR/0003/2008)