Journal article

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

Lars G Fritsche, Wilmar Igl, Jessica N Cooke Bailey, Felix Grassmann, Sebanti Sengupta, Jennifer L Bragg-Gresham, Kathryn P Burdon, Scott J Hebbring, Cindy Wen, Mathias Gorski, Ivana K Kim, David Cho, Donald Zack, Eric Souied, Hendrik PN Scholl, Elisa Bala, Kristine E Lee, David J Hunter, Rebecca J Sardell, Paul Mitchell Show all

NATURE GENETICS | NATURE PUBLISHING GROUP | Published : 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, mostly rare, protein-altering variants. 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. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for ..

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Grants

Awarded by Center for Inherited Diseases Research (CIDR) Program



Awarded by Medical Research Council


Awarded by National Institute for Health Research


Awarded by NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES


Awarded by NATIONAL EYE INSTITUTE


Awarded by NATIONAL HUMAN GENOME RESEARCH INSTITUTE


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Awarded by NATIONAL LIBRARY OF MEDICINE


Funding Acknowledgements

We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H.