Journal
NATURE GENETICS
Volume 45, Issue 3, Pages 314-318Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2554
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Funding
- MRC [MC_PC_U127561128, MC_U127584475] Funding Source: UKRI
- Chief Scientist Office [CZB/4/710, CZB/4/438] Funding Source: researchfish
- Fight for Sight [1329/30] Funding Source: researchfish
- Medical Research Council [MC_PC_U127561128, G9815508, MC_U127584475] Funding Source: researchfish
- National Institute for Health Research [SRF/01/010] Funding Source: researchfish
- Intramural NIH HHS Funding Source: Medline
- Medical Research Council [4882, G9815508, MC_U127584475, MC_PC_U127561128] Funding Source: Medline
- NCATS NIH HHS [UL1 TR001449, UL1 TR000041] Funding Source: Medline
- NEI NIH HHS [R01 EY018246, 1R01EY018246, P30EY11373, R01EY03083, K08 EY022943, R01 EY023196, 1K08EY022943‐01, N01EY92109, N01EY22112, EY016379, R21EY015145, R01 EY016482, R01EY01824601, P30 EY014800, R01 EY020483, R01EY020483, R01EY16482] Funding Source: Medline
- NHLBI NIH HHS [N01HC25195, N02HL64278] Funding Source: Medline
- NIDDK NIH HHS [N01 DK062204-A, N01‐DK‐6‐2204, R01 DK‐077510, R01 DK077510] Funding Source: Medline
- Wellcome Trust [076467, 08547508Z, WT083431MA, 085475B08Z, 092731, 083478, 090532, 076113] Funding Source: Medline
- Chief Scientist Office [CZB/4/710, CZB/4/438] Funding Source: Medline
- Department of Health [CDF-2009-02-35, SRF/01/010] Funding Source: Medline
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Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.
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