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.
| Original language | English |
|---|---|
| Pages (from-to) | 482-494 |
| Number of pages | 13 |
| Journal | American journal of human genetics |
| Volume | 74 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2004 |
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All Science Journal Classification (ASJC) codes
- Genetics
- Genetics(clinical)
Cite this
Age-Related Macular Degeneration : A High-Resolution Genome Scan for Susceptibility Loci in a Population Enriched for Late-Stage Disease. / Abecasis, Gonçalo R.; Yashar, Beverly M.; Zhao, Yu; Ghiasvand, Noor M.; Zareparsi, Sepideh; Branham, Kari E.H.; Reddick, Adam C.; Trager, Edward H.; Yoshida, Shigeo; Bahling, John; Filippova, Elena; Elner, Susan; Johnson, Mark W.; Vine, Andrew K.; Sieving, Paul A.; Jacobson, Samuel G.; Richards, Julia E.; Swaroop, Anand.
In: American journal of human genetics, Vol. 74, No. 3, 03.2004, p. 482-494.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Age-Related Macular Degeneration
T2 - A High-Resolution Genome Scan for Susceptibility Loci in a Population Enriched for Late-Stage Disease
AU - Abecasis, Gonçalo R.
AU - Yashar, Beverly M.
AU - Zhao, Yu
AU - Ghiasvand, Noor M.
AU - Zareparsi, Sepideh
AU - Branham, Kari E.H.
AU - Reddick, Adam C.
AU - Trager, Edward H.
AU - Yoshida, Shigeo
AU - Bahling, John
AU - Filippova, Elena
AU - Elner, Susan
AU - Johnson, Mark W.
AU - Vine, Andrew K.
AU - Sieving, Paul A.
AU - Jacobson, Samuel G.
AU - Richards, Julia E.
AU - Swaroop, Anand
PY - 2004/3
Y1 - 2004/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=12144288320&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12144288320&partnerID=8YFLogxK
U2 - 10.1086/382786
DO - 10.1086/382786
M3 - Article
C2 - 14968411
AN - SCOPUS:12144288320
VL - 74
SP - 482
EP - 494
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 3
ER -