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Cited by 335Retinal Diseases and TreatmentsGenetic Associations and EpidemiologyRetinal Development and Disorders

The DOI matches its Crossref record; 46 of the 48 references it cites were found in a registry or an index.

Cigarette Smoking Strongly Modifies the Association of LOC387715 and Age-Related Macular Degeneration

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Schmidt, Silke, Hauser, Michael A., Scott, William K., Postel, Eric A., Agarwal, Anita, Gallins, Paul, Wong, Frank, Chen, Yu Sarah, Spencer, Kylee, Schnetz-Boutaud, Nathalie, Haines, Jonathan L., Pericak-Vance, Margaret A.·2006·The American Journal of Human Genetics
DOI 10.1086/503822
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Abstract

We used iterative association mapping to identify a susceptibility gene for age-related macular degeneration (AMD) on chromosome 10q26, which is one of the most consistently implicated linkage regions for this disorder. We employed linkage analysis methods, followed by family-based and case-control association analyses, using two independent data sets. To identify statistically the most likely AMD-susceptibility allele, we used the Genotype-IBD Sharing Test (GIST) and conditional haplotype analysis. To incorporate the two most important known AMD risk factors--smoking and the Y402H variant of the complement factor H gene (CFH)--we used logistic regression modeling to test for gene-gene and gene-environment interactions in the case-control data set and used the ordered-subset analysis to account for genetic linkage heterogeneity in the family-based data set. Our results strongly implicate a coding change (Ala69Ser) in the LOC387715 gene as the second major identified AMD-susceptibility allele, confirming earlier suggestions. This variant's effect on AMD is statistically independent of CFH and is of similar magnitude to the effect of Y402H. The overall effect is driven primarily by a strong association in smokers, since we observed significant evidence for a statistical interaction between the LOC387715 variant and a history of cigarette smoking. This gene-environment interaction is supported by statistically independent family-based and case-control analysis methods. We estimate that CFH, LOC387715, and cigarette smoking together explain 61% of the population-attributable risk (PAR) of AMD. The adjusted PAR percentage estimates are 20% for smoking, 36% for LOC387715, and 43% for CFH. We demonstrate, for the first time, that a genetic susceptibility coupled with a modifiable lifestyle factor such as cigarette smoking confers a significantly higher risk of AMD than either factor alone.

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Metadata

Authors
Schmidt, S., Hauser, M. A., Scott, W. K., Postel, E. A., Agarwal, A., Gallins, P., Wong, F., Chen, Y. S., Spencer, K., Schnetz-Boutaud, N., Haines, J. L., & Pericak-Vance, M. A.
Affiliations
  • Duke Medical Center (US)
  • Vanderbilt University Medical Center (US)
Corresponding author
Schmidt, Silke
ORCID
Venue
The American Journal of Human Genetics
Publisher
Elsevier BV
Published
2006-05
Volume
78
Issue
5
Pages
852-864
ISSN
0002-9297 (ISSN-L)
DOI
10.1086/503822
OpenAlex
W2131861979
Cited by
335
References
48
Citations by year
2025: 2 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 2 · 2018: 7 · 2017: 4 · 2016: 8 · 2015: 13 · 2014: 27 · 2013: 28 · 2012: 30
FWCI
41.58
Type
journal article
Language
en
Open access
Licence
Locations
  • The American Journal of Human Genetics (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Medical Research Council
  • National Institute on Aging (AG-11268, P60AG011268)
  • National Eye Institute (R03EY015216, R01EY012118, EY015216, U10EY012118, EY12118)
  • National Center for Research Resources (M01RR000095, RR00095)
  • NIH Clinical Center
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
Keywords
age-related macular degeneration, LOC387715, cigarette smoking, gene-environment interaction, chromosome 10q26, complement factor H, genetic susceptibility, population attributable risk
MeSH terms
Aged, Aged, 80 and over, Chromosomes, Human, Pair 10, Female, Gene Frequency, Haplotypes, Homozygote, Humans, Genetic Linkage, Macular Degeneration, Male, Middle Aged, Proteins, Smoking, Genetic Variation, Case-Control Studies, Complement Factor H, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide

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