期刊
HUMAN MOLECULAR GENETICS
卷 20, 期 18, 页码 3699-3709出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddr270
关键词
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资金
- National Eye Institute
- National Institute of Mental Health [R01 MH67257, R01 MH59588, R01 MH59571, R01 MH59565, R01 MH59587, R01 MH60870, R01 MH59566, R01 MH59586, R01 MH61675, R01 MH60879, R01 MH81800, U01 MH46276, U01 MH46289, U01 MH46318, U01 MH79469, U01 MH79470]
- National Institutes of Health, Bethesda, MD, USA [RO1-EY11309, RO1-EY13435, R24-EY017404, P30-EY 001765, K12-EY16335]
- Massachusetts Lions Eye Research Fund, Inc.
- Research to Prevent Blindness, Inc., New York, NY, USA
- Foundation Fighting Blindness, Owing Mills, MD, USA
- Macula Vision Research Foundation
- Kaplen Foundation
- Widgeon Point Charitable Foundation
- Alcon Research Institute
- Fight for Sight
- National Health and Medical Research Council of Australia Centre for Clinical Research Excellence [529923]
- Victorian Government
- American Macular Degeneration Foundation
- Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service
- New England Eye Center
- Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA
Despite significant progress in the identification of genetic loci for age-related macular degeneration (AMD), not all of the heritability has been explained. To identify variants which contribute to the remaining genetic susceptibility, we performed the largest meta-analysis of genome-wide association studies to date for advanced AMD. We imputed 6 036 699 single-nucleotide polymorphisms with the 1000 Genomes Project reference genotypes on 2594 cases and 4134 controls with follow-up replication of top signals in 5640 cases and 52 174 controls. We identified two new common susceptibility alleles, rs1999930 on 6q21-q22.3 near FRK/COL10A1 [odds ratio (OR) 0.87; P = 1.1 x 10(-8)] and rs4711751 on 6p12 near VEGFA (OR 1.15; P = 8.7 x 10(-9)). In addition to the two novel loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB (rs641153), C3 (rs2230199), C2 (rs9332739), CFI (rs10033900), LIPC (rs10468017), TIMP3 (rs9621532) and CETP (rs3764261) were confirmed with genome-wide significant signals in this large study. Loci in the recently reported genes ABCA1 and COL8A1 were also detected with suggestive evidence of association with advanced AMD. The novel variants identified in this study suggest that angiogenesis (VEGFA) and extracellular collagen matrix (FRK/COL10A1) pathways contribute to the development of advanced AMD.
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