Evaluation of new and established age-related macular degeneration susceptibility genes in the Women'S Health Initiative Sight Exam (WHI-SE) study

Inga Peter, Gordon S. Huggins, Jose M. Ordovas, Mary Haan, Johanna M. Seddon

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Purpose: To assess whether established and newly reported genetic variants, independent of known lifestyle factors, are associated with the risk of age-related macular degeneration (AMD) among women participating in the Women's Health Initiative Sight Exam (WHI-SE) Genetic Ancillary Study. Design: Multicenter case-control study. Methods: One hundred and forty-six women with intermediate and late stages of AMD and 1269 subjects without AMD underwent ocular examinations and fundus photography to determine stage of AMD. Fourteen polymorphisms at or near 11 genes, including previously confirmed genes CFH, ARMS2/HTRA1, C2, C3, and CFI; recently reported AMD genes in the high-density lipoprotein cholesterol (HDL) pathway LIPC, ABCA1, CETP, and LPL; TIMP3/SYN3, a known ocular gene recently linked with AMD; and APOE, were assessed using logistic regression analysis. Results: After adjustment for demographic, behavioral, and other genetic factors, a protective effect was detected among TT carriers compared with non-carriers for the HDL pathway gene, LIPC rs493258, for intermediate and late AMD (OR [95% confidence interval]: 0.3 [0.20.7], P =.003). Variants in CFH rs1410996, ARMS2/HTRA1 A69S, and C3 R102G were significantly associated with an increased risk of AMD. Individuals with the homozygous CFI rs10033900 TT genotype had a 2.9 [1.27.2]-fold increased risk, and those with the CFH Y402H GG genotype had a 2.2 [1.04.8]-fold higher risk of developing AMD compared with non-carriers. APOE4 carriers may have a reduced risk of intermediate/late AMD (OR = 0.5 [0.30.9], P =.015. Suggestive associations were seen between AMD and the HDL pathway genes CETP and LPL. Conclusion: In this unique national cohort of women, we found associations with established AMD-related genetic factors and the recently reported LIPC gene in the HDL pathway. These findings may help develop novel therapeutic targets to treat or delay the onset of the disease.

Original languageEnglish
Pages (from-to)1005-1013.e1
JournalAmerican Journal of Ophthalmology
Issue number6
StatePublished - Dec 2011


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