Age-related maculopathy: an expanded genome-wide scan with evidence of susceptibility loci within the 1q31 and 17q25 regions
Abstract
Purpose We seek to identify genetic loci that contribute to age-related maculopathy susceptibility.Methods Families consisting of at least two siblings affected by age-related maculopathy were ascertained using eye care records and fundus photographs. Additional family members were used to increase the power to detect linkage. Microsatellite genotyping was conducted by the National Heart, Lung and Blood Institute Mammalian Genotyping Service and the National Institutes of Health Center for Inherited Disease Research. Linkage analyses were conducted with parametric (autosomal dominant; heterogeneity lod score) and nonparametric methods (S(all) statistic) using three diagnostic models. False-positive rates were determined from simulations using actual pedigrees and genotyping data.Results Under our least stringent diagnostic model, model C, 860 affected individuals from 391 families (452 sib pairs) were genotyped. Sixty-five percent of the affected individuals had evidence of exudative disease. Four regions, 1q31, 9p13, 10q26, and 17q25, showed multipoint heterogeneity lod scores or S(all) scores of 2.0 or greater (under at least one model). Under our most stringent diagnostic model, model A, the 1q31 heterogeneity lod score was 2.46 between D1S1660 and D1S1647. Under model C, the 17q25 heterogeneity lod score at D17S928 was 3.16. Using a threshold of 1.5, additional loci on chromosomes 2 and 12 were identified.Conclusions The locus on chromosome 1q31 independently confirms a report by Klein and associates mapping an age-related maculopathy susceptibility gene to this region. Simulations indicate that the 1q31 and 17q25 loci are unlikely to be false positives. There was no evidence that other known macular or retinal dystrophy candidate gene regions are major contributors to the genetics of age-related maculopathy.
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Several genome-wide linkage scans for AMD have found suggestive linkage on chromosome 1q.
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From CFH Y402H confers similar risk of soft drusen and both forms of advanced AMD (2005) · cites this paper as [10]
Cites
A simple salting out procedure for extracting DNA from human nucleated cells
Miller, S. A., Dykes, D. D., & Polesky, H. F. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.3.1215 · Cited by 20,341 · see citing works
PedCheck: A Program for Identification of Genotype Incompatibilities in Linkage Analysis
O'Connell, J. R., & Weeks, D. E. (1998) · The American Journal of Human Genetics · doi:10.1086/301904 · Cited by 2,063 · see citing works
Self-citationSobel, E. M., & Lange, K. L. (1996) · PubMed Central · Cited by 1,176 · see citing works
The Framingham Eye Study. I. Outline and major prevalence findings.
Kahn, H. A., Leibowitz, H., Ganley, J., Kini, M., Colton, T., Nickerson, R. S., & Dawber, T. (1977) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a112428 · Cited by 821 · see citing works
Allegro, a new computer program for multipoint linkage analysis
Gudbjartsson, D. F., Jónasson, K., Frigge, M. L., & Kong, A. (2000) · Nature Genetics · doi:10.1038/75514 · Cited by 785 · see citing works
Drusen and Disciform Macular Detachment and Degeneration
Gass, J. D. M. (1973) · Archives of Ophthalmology · doi:10.1001/archopht.1973.01000050208006 · Cited by 593 · see citing works
Genetic Association of Apolipoprotein E with Age-Related Macular Degeneration
Klaver, C. C. W., Kliffen, M., van Duijn, C. M., Hofman, A., Cruts, M., Grobbee, D. E., van Broeckhoven, C., & de Jong, P. T. V. M. (1998) · The American Journal of Human Genetics · doi:10.1086/301901 · Cited by 498 · see citing works
Statistical Tests for Detection of Misspecified Relationships by Use of Genome-Screen Data
McPeek, M. S., & Sun, L. (2000) · The American Journal of Human Genetics · doi:10.1086/302800 · Cited by 336 · see citing works
Genetic Risk of Age-related Maculopathy: Population-Based Familial Aggregation Study
Klaver, C. C. W. (1998) · Archives of Ophthalmology · doi:10.1001/archopht.116.12.1646 · Cited by 323 · see citing works
Souied, E. H., Benlian, P., Amouyel, P., Feingold, J., Lagarde, J.-P., Munnich, A., Kaplan, J., Coscas, G., & Soubrane, G. (1998) · American Journal of Ophthalmology · doi:10.1016/s0002-9394(99)80146-9 · Cited by 292 · see citing works
Cataracts and Macular Degeneration in Older Americans
Klein, R., & Klein, R. (1982) · Archives of Ophthalmology · doi:10.1001/archopht.1982.01030030573002 · Cited by 276 · see citing works
Sibling correlations and segregation analysis of age‐related maculopathy: The beaver dam eye study
Heiba, I. M., Elston, R. C., Klein, B. E. K., & Klein, R. (1994) · Genetic Epidemiology · doi:10.1002/gepi.1370110106 · Cited by 259 · see citing works
Age-related Macular Degeneration: Clinical Features in a Large Family and Linkage to Chromosome 1q
Klein, M. L. (1998) · Archives of Ophthalmology · doi:10.1001/archopht.116.8.1082 · Cited by 252 · see citing works
Strategies for characterizing highly polymorphic markers in human gene mapping.
Ott, J. (1992) · PubMed · Cited by 236 · see citing works
A Twin Study of Age-related Macular Degeneration
Meyers, S. M., Greene, T., & Gutman, F. A. (1995) · American Journal of Ophthalmology · doi:10.1016/s0002-9394(14)72729-1 · Cited by 210 · see citing works
Heredity and Age-Related Macular Degeneration: Observations in Monozygotic Twins
Klein, M. L. (1994) · Archives of Ophthalmology · doi:10.1001/archopht.1994.01090190080025 · Cited by 207 · see citing works
A Multipoint Method for Detecting Genotyping Errors and Mutations in Sibling-Pair Linkage Data
Douglas, J. A., Boehnke, M., & Lange, K. L. (2000) · The American Journal of Human Genetics · doi:10.1086/302861 · Cited by 180 · see citing works
Prevalence of Ocular Disease in a Population Study of Subjects 65 Years Old and Older
Martinez, G. S., Campbell, A. J., Reinken, J., & Allan, B. C. (1982) · American Journal of Ophthalmology · doi:10.1016/0002-9394(82)90073-3 · Cited by 153 · see citing works
A full genome scan for age-related maculopathy
Weeks, D. E. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.9.1329 · Cited by 137 · see citing works
Self-citationHodge, S. E., Anderson, C. E., Neiswanger, K., Sparkes, R. S., & Rimoin, D. L. (1983) · PubMed · Cited by 123 · see citing works
Schmidt, S., Saunders, A. M., Paz, L. P. M. D. L., Postel, E. A., Heinis, R. M., Agarwal, A., Scott, W. K., Gilbert, J. R., McDowell, J., Bazyk, A., et al. (2000) · PubMed · Cited by 115 · see citing works
Senile Lens and Senile Macular Changes in a Population-Based Sample
Sperduto, R. D., & SEIGEL, D. G. (1980) · American Journal of Ophthalmology · doi:10.1016/s0002-9394(14)75081-0 · Cited by 114 · see citing works
Linkage analysis in the presence of errors III: marker loci and their map as nuisance parameters.
Göring, H., & Terwilliger, J. (2000) · American Journal of Human Genetics · doi:10.1086/302846 · Cited by 107 · see citing works
Genetic susceptibility to age related macular degeneration
Yates, J., & Moore, A. (2000) · Journal of Medical Genetics · doi:10.1136/jmg.37.2.83 · Cited by 99 · see citing works
Age‐related macular degeneration. Macular changes, prevalence and sex ratio
Vinding, T. (1989) · Acta Ophthalmologica · doi:10.1111/j.1755-3768.1989.tb04392.x · Cited by 90 · see citing works
Pang, C. P., Baum, L., Chan, W., Lau, T.-C., Poon, P. M. K., & Lam, D. S. C. (2000) · Ophthalmologica · doi:10.1159/000027506 · Cited by 79 · see citing works
Vision in the elderly and its use in the social environment.
Häkkinen, L. (1984) · PubMed · Cited by 75 · see citing works
Effects of Stratification in the Analysis of Affected-Sib-Pair Data: Benefits and Costs
Leal, S. M., & Ott, J. (2000) · The American Journal of Human Genetics · doi:10.1086/302748 · Cited by 69 · see citing works
Phenotypic Heterogeneity in Families with Age-related Macular Degeneration
Paz, M. A. D. L., Pericak‐Vance, M. A., Haines, J. L., & Seddon, J. M. (1997) · American Journal of Ophthalmology · doi:10.1016/s0002-9394(14)70825-6 · Cited by 37 · see citing works
Estimation of allele frequencies with data on sibships
Broman, K. W. (2001) · Genetic Epidemiology · doi:10.1002/gepi.2 · Cited by 35 · see citing works
A practice-based survey of familial age-related maculopathy
Keverline, M. R., Mah, T. S., Keverline, P. O., & Gorin, M. B. (1998) · Ophthalmic Genetics · doi:10.1076/opge.19.1.19.2176 · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501536102 · Cited by 1,961 · see citing works
Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies
Ambati, J., Ambati, B. K., Yoo, S. H., Ianchulev, S., & Adamis, A. P. (2003) · Survey of Ophthalmology · doi:10.1016/s0039-6257(03)00030-4 · Cited by 959 · see citing works
Rivera, A., Fisher, S. A., Fritsche, L. G., Keilhauer, C. N., Lichtner, P., Meitinger, T., & Weber, B. H. F. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi353 · Cited by 788 · see citing works
Maller, J., George, S., Purcell, S., Fagerness, J., Altshuler, D., Daly, M. J., & Seddon, J. M. (2006) · Nature Genetics · doi:10.1038/ng1873 · Cited by 599 · see citing works
Seddon, J. M. (2005) · Archives of Ophthalmology · doi:10.1001/archopht.123.3.321 · Cited by 446 · see citing works
Li, M., Atmaca-Sonmez, P., Othman, M., Branham, K. E. H., Khanna, R., Wade, M. S., Li, Y., Liang, L., Zareparsi, S., Swaroop, A., et al. (2006) · Nature Genetics · doi:10.1038/ng1871 · Cited by 354 · see citing works
Photoreceptor degeneration and dysfunction in aging and age-related maculopathy
Jackson, G. R., Owsley, C., & Curcio, C. A. (2002) · Ageing Research Reviews · doi:10.1016/s1568-1637(02)00007-7 · Cited by 317 · see citing works
The Genetics of Age-Related Macular Degeneration: A Review of Progress to Date
Haddad, S., Chen, C. A., Santangelo, S. L., & Seddon, J. M. (2006) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2006.05.001 · Cited by 299 · see citing works
Meta-analysis of genome scans of age-related macular degeneration
Fisher, S. A., Abecasis, G. R., Yashar, B. M., Zareparsi, S., Swaroop, A., Iyengar, S. K., Klein, B. E. K., Klein, R., Lee, K. E., Majewski, J., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi230 · Cited by 239 · see citing works
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Magnusson, K. P., Duan, S., Sigurdsson, H., Petursson, H., Yang, Z., Zhao, Y., Bernstein, P. S., Ge, J., Jonasson, F., Stefansson, E., et al. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0030005 · Cited by 226 · see citing works
Seddon, J. M., Santangelo, S. L., Book, K., Chong, S., & Cote, J. (2003) · The American Journal of Human Genetics · doi:10.1086/378505 · Cited by 208 · see citing works
Age-related macular degeneration–a genome scan in extended families
Majewski, J., Schultz, D. W., Weleber, R. G., Schain, M. B., Edwards, A. O., Matise, T. C., Acott, T. S., Ott, J., & Klein, M. L. (2003) · The American Journal of Human Genetics · doi:10.1086/377701 · Cited by 201 · see citing works
Weeks, D. E., Conley, Y. P., Tsai, H.-J., Mah, T. S., Schmidt, S., Postel, E. A., Agarwal, A., Haines, J. L., Pericak-Vance, M. A., Rosenfeld, P. J., et al. (2004) · The American Journal of Human Genetics · doi:10.1086/422476 · Cited by 195 · see citing works
Self-citationHaines, J. L., Schnetz-Boutaud, N., Schmidt, S., Scott, W. K., Agarwal, A., Postel, E. A., Olson, L., Kenealy, S. J., Hauser, M., Gilbert, J. R., et al. (2006) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.05-0116 · Cited by 189 · see citing works
Abecasis, G. R., Yashar, B. M., Zhao, Y., Ghiasvand, N. M., Zareparsi, S., Branham, K. E. H., Reddick, A. C., Trager, E. H., Yoshida, S., Bahling, J., et al. (2004) · The American Journal of Human Genetics · doi:10.1086/382786 · Cited by 182 · see citing works
Iyengar, S. K., Song, D., Klein, B. E. K., Klein, R., Schick, J. H., Humphrey, J., Millard, C., Liptak, R., Russo, K., Jun, G., et al. (2004) · The American Journal of Human Genetics · doi:10.1086/380912 · Cited by 173 · see citing works
Conley, Y. P., Thalamuthu, A., Jakobsdottir, J., Weeks, D. E., Mah, T., Ferrell, R. E., & Gorin, M. B. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi204 · Cited by 158 · see citing works
Self-citationConley, Y. P., Jakobsdottir, J., Mah, T., Weeks, D. E., Klein, R., Kuller, L., Ferrell, R. E., & Gorin, M. B. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl396 · Cited by 157 · see citing works
Self-citationZareparsi, S. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.03-1253 · Cited by 145 · see citing works
The Prevalence of Age-Related Maculopathy in Iceland: Reykjavik Eye Study
Jonasson, F. (2003) · Archives of Ophthalmology · doi:10.1001/archopht.121.3.379 · Cited by 106 · see citing works
Genetics of age-related macular degeneration: current concepts, future directions
DeAngelis, M. M., Silveira, A. C., Carr, E. A., & Kim, I. K. (2011) · Seminars in Ophthalmology · doi:10.3109/08820538.2011.577129 · Cited by 94 · see citing works
Francis, P. J., George, S., Schultz, D. W., Rosner, B., Hamon, S., Ott, J., Weleber, R. G., Klein, M. L., & Seddon, J. M. (2007) · Human Heredity · doi:10.1159/000100046 · Cited by 91 · see citing works
Schmidt, S., Scott, W. K., Postel, E. A., Agarwal, A., Hauser, E. R., De La Paz, M. A., Gilbert, J. R., Weeks, D. E., Gorin, M. B., Haines, J. L., et al. (2004) · BMC Genetics · doi:10.1186/1471-2156-5-18 · Cited by 60 · see citing works
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- Authors
- Weeks, D. E., Conley, Y. P., Tsai, H.-J., Mah, T. S., Rosenfeld, P. J., Paul, T. O., Eller, A. W., Morse, L. S., Dailey, J. P., Ferrell, R. E., & Gorin, M. B.
- Affiliations
- University of Pittsburgh (US)
- University of Miami (US)
- Smith-Kettlewell Eye Research Institute (US)
- University of California, Davis (US)
- Case Western Reserve University (US)
- Corresponding author
- Gorin, Michael B
- ORCID
- Venue
- American Journal of Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 132
- Issue
- 5
- Pages
- 682-692
- ISSN
- 0002-9394 (ISSN-L)
- OpenAlex
- W2047282046
- Cited by
- 140
- References
- 31
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 4 · 2013: 2 · 2012: 5
- FWCI
- 9.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01hg065403-000, n01hv048141-009)
- National Heart, Lung, and Blood Institute (N01-HV48141)
- National Human Genome Research Institute (N01 HG-65403)
- National Eye Institute (R01-EY 09859, R01EY009859)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- age-related maculopathy, genetic susceptibility loci, chromosome 17q25, linkage analysis, chromosome 10q26
- MeSH terms
- Aged, Chromosome Mapping, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 17, Female, Genotype, Humans, Genetic Linkage, Lod Score, Macular Degeneration, Male, Middle Aged, Pedigree, Cohort Studies, Genome, Genetic Predisposition to Disease
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