Rapid Dissection of the Genetic Risk of Age-Related Macular Degeneration
Abstract
Debra A. Schaumberg, ScD, OD, MPH; Susan E. Hankinson, ScD; Qun Guo, MSc; Eric Rimm, ScD; David J. Hunter, MBBS, ScDObjectivesTo delineate the magnitude of susceptibility to age-related macular degeneration (AMD) due to common variants in the gene for complement factor H (CFH) and the predicted gene LOC387715 and to determine whether these variants interact with modifiable risk factors.MethodsWe compared cases who developed AMD (n = 457) with 1071 age- and sex-matched control subjects in a prospective nested case-control study within the Nurses' Health Study and the Health Professionals Follow-up Study. We determined the incidence rate ratios and 95% confidence intervals (CIs) for AMD for each genotype and examined the interactions with modifiable risk factors.ResultsParticipants with 1 or 2 copies of the Y402H variant of CFH were, respectively, 1.98 (95% CI, 1.64-2.40) and 3.92 (95% CI, 2.69-5.76) times more likely to develop AMD, whereas the incident rate ratios (95% CIs) for 1 and 2 copies of LOC387715 A69S were 2.38 (1.92-2.96) and 5.66 (3.69-8.76), respectively. The fraction of AMD cases attributable to these 2 variants was 63% (95% CI, 58%-68%). Subjects homozygous for both risk alleles had a 50-fold increased risk of AMD (95% CI, 10.8-237), and cigarette smoking and obesity multiplied the risks associated with these variants.ConclusionAge-related macular degeneration has emerged as a paradigmatic example of a common disease caused by the interplay of genetic predisposition and exposure to modifiable risk factors.
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We further confirmed the association with family history of AMD.
“We further confirmed the association with family history of AMD, consistent with the growing recognition of major genes involved in AMD (e.g., complement factor H and C3, LOCS 3877, HTRA 1) [21,83-86].”
From Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis (2010) · cites this paper as [84]
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- Authors
- Haines, J. L., & Pericak-Vance, M. A.
- Affiliations
- Vanderbilt University Medical Center (US)
- ORCID
- Haines, Jonathan L.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2007-01-24
- Volume
- 297
- Issue
- 4
- Pages
- 401
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W1984675740
- Cited by
- 5
- References
- 15
- Citations by year
- 2020: 1 · 2015: 1
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- 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 macular degeneration, genetic susceptibility, complement factor H, LOC387715, risk alleles, gene-environment interaction, cigarette smoking, obesity, modifiable risk factors, attributable fraction, Nurses' Health Study, Health Professionals Follow-up Study
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