Age-Related Macular Degeneration: A High-Resolution Genome Scan for Susceptibility Loci in a Population Enriched for Late-Stage Disease

Gonçalo R. Abecasis, Beverly M. Yashar, Yu Zhao, Noor M. Ghiasvand, Sepideh Zareparsi, Kari E.H. Branham, Adam C. Reddick, Edward H. Trager, Shigeo Yoshida, John Bahling, Elena Filippova, Susan Elner, Mark W. Johnson, Andrew K. Vine, Paul A. Sieving, Samuel G. Jacobson, Julia E. Richards, Anand Swaroop

研究成果: Contribution to journalArticle査読

139 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)482-494
ページ数13
ジャーナルAmerican journal of human genetics
74
3
DOI
出版ステータス出版済み - 3 2004
外部発表はい

All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 遺伝学(臨床)

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