{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:15:47Z","timestamp":1785215747560,"version":"3.55.0"},"reference-count":72,"publisher":"Oxford University Press (OUP)","issue":"4","funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["ZIAEY000546"],"award-info":[{"award-number":["ZIAEY000546"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["ZIAEY000489"],"award-info":[{"award-number":["ZIAEY000489"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY031209"],"award-info":[{"award-number":["R01EY031209"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK Biobank Resource","award":["24460"],"award-info":[{"award-number":["24460"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Genome-wide association studies have contributed extensively to the discovery of disease-associated common variants. However, the genetic contribution to complex traits is still largely difficult to interpret. We report a genome-wide association study of 2394 cases and 2393 controls for age-related macular degeneration (AMD) via whole-genome sequencing, with 46.9 million genetic variants. Our study reveals significant single-variant association signals at four loci and independent gene-based signals in CFH, C2, C3, and NRTN. Using data from the Exome Aggregation Consortium (ExAC) for a gene-based test, we demonstrate an enrichment of predicted rare loss-of-function variants in CFH, CFI, and an as-yet unreported gene in AMD, ORMDL2. Our method of using a large variant list without individual-level genotypes as an external reference provides a flexible and convenient approach to leverage the publicly available variant datasets to augment the search for rare variant associations, which can explain additional disease risk in AMD.<\/jats:p>","DOI":"10.1093\/hmg\/ddad189","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T19:28:34Z","timestamp":1699385314000},"page":"374-385","source":"Crossref","is-referenced-by-count":12,"title":["Whole genome sequencing of 4,787 individuals identifies gene-based rare variants in age-related macular degeneration"],"prefix":"10.1093","volume":"33","author":[{"given":"Alan","family":"Kwong","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Center for Statistical Genetics, University of Michigan , 1415 Washington Heights, Ann Arbor, MI 48109 , United 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Epidemiology and Cost Center , Department of Internal Medicine-Nephrology, , 1415 Washington Heights, Ann Arbor, MI 48109 , United States"},{"name":"University of Michigan , Department of Internal Medicine-Nephrology, , 1415 Washington Heights, Ann Arbor, MI 48109 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari E","family":"Branham","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Michigan Kellogg Eye Center , 1000 Wall St, Ann Arbor, MI 48105 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayshree","family":"Advani","sequence":"additional","affiliation":[{"name":"Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health , 6 Center Drive, MSC 0610, Bethesda, MD 20892 , United 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Ophthalmology , Perelman School of Medicine, , 51 N. 39th Street, Philadelphia, PA 19104 , United States"},{"name":"University of Pennsylvania Medical School , Perelman School of Medicine, , 51 N. 39th Street, Philadelphia, PA 19104 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily Y","family":"Chew","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Clinical Application, National Eye Institute, National Institutes of Health , 10 Center Drive Building 10-CRC, Bethesda, MD 20892 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gon\u00e7alo R","family":"Abecasis","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Center for Statistical Genetics, University of Michigan , 1415 Washington Heights, Ann Arbor, MI 48109 , United States"},{"name":"Regeneron Pharmaceuticals Inc. , 777 Old Saw Mill River Rd, Tarrytown, NY 10591 , United 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