Abstract
Age-related maculopathy (ARM), or age-related macular degeneration, is one of the most common causes of visual impairment in the elderly population of developed nations. In a combined analysis of two previous genomewide scans that included 391 families, containing up to 452 affected sib pairs, we found linkage evidence in four regions: 1q31, 9p13, 10q26, and 17q25. We now have added a third set of families and have performed an integrated analysis incorporating 530 families and up to 736 affected sib pairs. Under three diagnostic models, we have conducted linkage analyses using parametric (heterogeneity LOD [HLOD] scores under an autosomal dominant model) and nonparametric (S α∥ statistic) methods. There is ongoing evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions. If we treat the third set of families as a replication set, then two regions (10q26 and 17q25) are replicated, with LOD scores >1.0. If we pool all our data together, then four regions (1q31, 2q14.3, 10q26, and 17q25) show HLOD or S α∥ scores ≥2.0. Within the 1q31 region, we observed an HLOD of 2.72 (genomewide P = .061) under our least stringent diagnostic model, whereas the 17q25 region contained a maximal HLOD of 3.53 (genomewide P = .007) under our intermediate diagnostic model. We have evaluated our results with respect to the findings from several new independent genomewide linkage studies and also have completed ordered subset analyses (OSAs) with apolipoprotein E alleles, smoking history, and age at onset as stratifying covariates. The OSAs generate the interesting hypothesis that the effect of smoking on the risk of ARM is accentuated by a gene in the 10q26 region-a region implicated by four other studies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 174-189 |
| Number of pages | 16 |
| Journal | American Journal of Human Genetics |
| Volume | 75 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 2004 |
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ASJC Scopus subject areas
- Genetics
Cite this
Age-related maculopathy : A genomewide scan with continued evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions. / Weeks, Daniel E.; Conley, Yvette P.; Tsai, Hui Ju; Mah, Tammy S.; Schmidt, Silke; Postel, Eric A.; Agarwal, Anita; Haines, Jonathan L.; Pericak-Vance, Margaret A.; Rosenfeld, Philip J.; Paul, T. Otis; Eller, Andrew W.; Morse, Lawrence S; Dailey, J. P.; Ferrell, Robert E.; Gorin, Michael B.
In: American Journal of Human Genetics, Vol. 75, No. 2, 08.2004, p. 174-189.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Age-related maculopathy
T2 - A genomewide scan with continued evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions
AU - Weeks, Daniel E.
AU - Conley, Yvette P.
AU - Tsai, Hui Ju
AU - Mah, Tammy S.
AU - Schmidt, Silke
AU - Postel, Eric A.
AU - Agarwal, Anita
AU - Haines, Jonathan L.
AU - Pericak-Vance, Margaret A.
AU - Rosenfeld, Philip J.
AU - Paul, T. Otis
AU - Eller, Andrew W.
AU - Morse, Lawrence S
AU - Dailey, J. P.
AU - Ferrell, Robert E.
AU - Gorin, Michael B.
PY - 2004/8
Y1 - 2004/8
N2 - Age-related maculopathy (ARM), or age-related macular degeneration, is one of the most common causes of visual impairment in the elderly population of developed nations. In a combined analysis of two previous genomewide scans that included 391 families, containing up to 452 affected sib pairs, we found linkage evidence in four regions: 1q31, 9p13, 10q26, and 17q25. We now have added a third set of families and have performed an integrated analysis incorporating 530 families and up to 736 affected sib pairs. Under three diagnostic models, we have conducted linkage analyses using parametric (heterogeneity LOD [HLOD] scores under an autosomal dominant model) and nonparametric (S α∥ statistic) methods. There is ongoing evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions. If we treat the third set of families as a replication set, then two regions (10q26 and 17q25) are replicated, with LOD scores >1.0. If we pool all our data together, then four regions (1q31, 2q14.3, 10q26, and 17q25) show HLOD or S α∥ scores ≥2.0. Within the 1q31 region, we observed an HLOD of 2.72 (genomewide P = .061) under our least stringent diagnostic model, whereas the 17q25 region contained a maximal HLOD of 3.53 (genomewide P = .007) under our intermediate diagnostic model. We have evaluated our results with respect to the findings from several new independent genomewide linkage studies and also have completed ordered subset analyses (OSAs) with apolipoprotein E alleles, smoking history, and age at onset as stratifying covariates. The OSAs generate the interesting hypothesis that the effect of smoking on the risk of ARM is accentuated by a gene in the 10q26 region-a region implicated by four other studies.
AB - Age-related maculopathy (ARM), or age-related macular degeneration, is one of the most common causes of visual impairment in the elderly population of developed nations. In a combined analysis of two previous genomewide scans that included 391 families, containing up to 452 affected sib pairs, we found linkage evidence in four regions: 1q31, 9p13, 10q26, and 17q25. We now have added a third set of families and have performed an integrated analysis incorporating 530 families and up to 736 affected sib pairs. Under three diagnostic models, we have conducted linkage analyses using parametric (heterogeneity LOD [HLOD] scores under an autosomal dominant model) and nonparametric (S α∥ statistic) methods. There is ongoing evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions. If we treat the third set of families as a replication set, then two regions (10q26 and 17q25) are replicated, with LOD scores >1.0. If we pool all our data together, then four regions (1q31, 2q14.3, 10q26, and 17q25) show HLOD or S α∥ scores ≥2.0. Within the 1q31 region, we observed an HLOD of 2.72 (genomewide P = .061) under our least stringent diagnostic model, whereas the 17q25 region contained a maximal HLOD of 3.53 (genomewide P = .007) under our intermediate diagnostic model. We have evaluated our results with respect to the findings from several new independent genomewide linkage studies and also have completed ordered subset analyses (OSAs) with apolipoprotein E alleles, smoking history, and age at onset as stratifying covariates. The OSAs generate the interesting hypothesis that the effect of smoking on the risk of ARM is accentuated by a gene in the 10q26 region-a region implicated by four other studies.
UR - http://www.scopus.com/inward/record.url?scp=3242703945&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3242703945&partnerID=8YFLogxK
U2 - 10.1086/422476
DO - 10.1086/422476
M3 - Article
C2 - 15168325
AN - SCOPUS:3242703945
VL - 75
SP - 174
EP - 189
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 2
ER -