School of Medicine Publications and Presentations
Document Type
Article
Publication Date
2-2016
Abstract
Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. Here, we report on a study of >12 million variants including 163,714 directly genotyped, most rare, protein-altering variant. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5×10–8) distributed across 34 loci. While wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first signal specific to wet AMD, near MMP9 (difference-P = 4.1×10–10). Very rare coding variants (frequency < 0.1%) in CFH, CFI, and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
Recommended Citation
Fritsche, L. G., Igl, W., Bailey, J. N. C., Grassmann, F., Sengupta, S., Bragg-Gresham, J. L., Burdon, K. P., Hebbring, S. J., Wen, C., Gorski, M., Kim, I. K., Cho, D., Zack, D., Souied, E., Scholl, H. P. N., Bala, E., Lee, K. E., Hunter, D. J., Sardell, R. J., … Heid, I. M. (2015). A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. In Nature Genetics (Vol. 48, Issue 2, pp. 134–143). Springer Science and Business Media LLC. https://doi.org/10.1038/ng.3448
Publication Title
Nature Genetics
DOI
10.1038/ng.3448
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
Original published version available at https://doi.org/10.1038/ng.3448