@article{e4b8a03d856646a6bc406ed01620c47a,
title = "Age-Related Macular Degeneration: A High-Resolution Genome Scan for Susceptibility Loci in a Population Enriched for Late-Stage Disease",
abstract = "Age-related macular degeneration (AMD) is a complex multifactorial disease that affects the central region of the retina. AMD is clinically heterogeneous, leading to geographic atrophy (GA) and/or choroidal neovascularization (CNV) at advanced stages. Considerable data exists in support of a genetic predisposition for AMD. Recent linkage studies have provided evidence in favor of several AMD susceptibility loci. We have performed a high-resolution (5-cM) genome scan of 412 affected relative pairs that were enriched for late-stage disease (GA and/or CNV). Nonparametric linkage analysis was performed using two different diagnostic criteria and also by dividing the affected individuals according to GA or CNV phenotype. Our results demonstrate evidence of linkage in regions that were suggested in at least one previous study at chromosomes 1q (236-240 cM in the Marshfield genetic map), 5p (40-50 cM), and 9q (111 cM). Multipoint analysis of affected relatives with CNV provided evidence of additional susceptibility loci on chromosomes 2p (10 cM) and 22q (25 cM). A recently identified Gln5345Arg change in HEMICENTIN-1 on chromosome 1q25 was not detected in 274 affected members in the restricted group with AMD, 346 additional patients with AMD, and 237 unaffected controls. Our results consolidate the chromosomal locations of several AMD susceptibility loci and, together with previous reports, should facilitate the search for disease-associated sequence variants.",
author = "Abecasis, {Gon{\c c}alo R.} and Yashar, {Beverly M.} and Yu Zhao and Ghiasvand, {Noor M.} and Sepideh Zareparsi and Branham, {Kari E.H.} and Reddick, {Adam C.} and Trager, {Edward H.} and Shigeo Yoshida and John Bahling and Elena Filippova and Susan Elner and Johnson, {Mark W.} and Vine, {Andrew K.} and Sieving, {Paul A.} and Jacobson, {Samuel G.} and Richards, {Julia E.} and Anand Swaroop",
note = "Funding Information: We are grateful to numerous individuals and families who generously donated their time and resources. We thank Drs. Paul R. Lichter, Ron Kurtz, Don Puro, Michael Smith Wheelock, David Zacks, and Stephen Saxe; Ms. Kathryn B. Moore and Laurie Jessup, for their efforts in patient collection; many retina physicians in the State of Michigan and the Great Lakes region, for their support of this project; and the clinical staff at the Kellogg Eye Center Retina Clinic, whose assistance made this work possible. We acknowledge Dr. Michael Boehnke and Heather Stringham, for their suggestions and input during the early stages of the project, and Ms. Sharyn Ferrara, for administrative assistance. The genomewide scan was performed by the NHLBI Mammalian Genotyping Service ( http://research.marshfieldclinic.org/genetics/ ), under the direction of Dr. James Weber. This research was supported by grants from the Macula Vision Research Foundation (West Conshohocken, PA), the Foundation Fighting Blindness (Owings Mills, MD), the Elmer and Sylvia Sramek Charitable Foundation (Chicago, IL), the National Institutes of Health (F32-EY014085), the American Federation for Aging Research (New York, NY), Research to Prevent Blindness (New York, NY), and the Harold F. Falls Collegiate Professorship. ",
year = "2004",
month = mar,
doi = "10.1086/382786",
language = "English",
volume = "74",
pages = "482--494",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "3",
}