Study Report - GWAS of age-related macular degeneration (HGVST501)
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Explore Study in Browser| Identifier | HGVST501 | |||||||||||||||||||||||
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| Study name | GWAS of age-related macular degeneration | |||||||||||||||||||||||
| Total p-values imported | 11 | |||||||||||||||||||||||
| Phenotype(s) tested | Age-related macular degeneration |
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| Study design | Case and control with replication | |||||||||||||||||||||||
| Genotype platforms |
Affymetrix 632,932 | |||||||||||||||||||||||
| Abstract | Advanced age-related macular degeneration (AMD) is the leading cause of late onset blindness. We present results of a genome-wide association study of 979 advanced AMD cases and 1,709 controls using the Affymetrix 6.0 platform with replication in seven additional cohorts (totaling 5,789 unrelated cases and 4,234 unrelated controls). We also present a comprehensive analysis of copy-number variations and polymorphisms for AMD. Our discovery data implicated the association between AMD and a variant in the hepatic lipase gene (LIPC) in the high-density lipoprotein cholesterol (HDL) pathway (discovery P = 4.53e-05 for rs493258). Our LIPC association was strongest for a functional promoter variant, rs10468017, (P = 1.34e-08), that influences LIPC expression and serum HDL levels with a protective effect of the minor T allele (HDL increasing) for advanced wet and dry AMD. The association we found with LIPC was corroborated by the Michigan/Penn/Mayo genome-wide association study; the locus near the tissue inhibitor of metalloproteinase 3 was corroborated by our replication cohort for rs9621532 with P = 3.71e-09. We observed weaker associations with other HDL loci (ABCA1, P = 9.73e-04; cholesterylester transfer protein, P = 1.41e-03; FADS1-3, P = 2.69e-02). Based on a lack of consistent association between HDL increasing alleles and AMD risk, the LIPC association may not be the result of an effect on HDL levels, but it could represent a pleiotropic effect of the same functional component. Results implicate different biologic pathways than previously reported and provide new avenues for prevention and treatment of AMD. | |||||||||||||||||||||||
| Submission information |
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| Related links |
NHGRI GWAS catalog study annotation for HGVST501 |
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| Background | Not supplied | |||||||||||||||||||||||
| Objectives | Not supplied | |||||||||||||||||||||||
| Key results | Not supplied | |||||||||||||||||||||||
| Conclusions | Not supplied | |||||||||||||||||||||||
| Reason for study size | Not supplied | |||||||||||||||||||||||
| Study power | Not supplied | |||||||||||||||||||||||
| Sources of bias | Not supplied | |||||||||||||||||||||||
| Limitations | Not supplied | |||||||||||||||||||||||
| Acknowledgements | Not supplied | |||||||||||||||||||||||
| Related citations |
Neale BM, Fagerness J, Reynolds R et al.
Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC). Proceedings of the National Academy of Sciences of the United States of America 2010;107(16):7395-400
Hindorff LA, Sethupathy P, Junkins HA et al.
Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proceedings of the National Academy of Sciences U S A. 2009 May 27 |
