A search for age-related macular degeneration risk variants in Alzheimer disease genes and pathways

作者：Logue Mark W; Schu Matthew; Vardarajan Badri N; Farrell John; Lunetta Kathryn L; Jun Gyungah; Baldwin Clinton T; DeAngelis Margaret M; Farrer Lindsay A^*

来源：Neurobiology of Aging, 2014, 35(6): 1510.e7.

DOI：10.1016/j.neurobiolaging.2013.12.007

• Alzheimer disease
• Age related macular degeneration
• Genetic association
• Gene-based test
• Pathway analysis

Several lines of inquiry point to overlapping molecular mechanisms between late-onset Alzheimer disease (AD) and age-related macular degeneration (AMD). We evaluated summarized results from large genome-wide association studies for AD and AMD to test the hypothesis that AD susceptibility loci are also associated with AMD. We observed association of both disorders with genes in a region of chromosome 7, including PILRA and ZCWPW1 (peak AMD SNP rs7792525, minor allele frequency [MAF] 19%, odds ratio [OR] 1.14, p 2.34 x 10(-6)), and with ABCA7 (peak AMD SNP rs3752228, MAF = 0.054, OR 1.22, p 0.00012). Next, we evaluated association of AMD with genes in AD-related pathways identified by canonical pathway analysis of AD-associated genes. Significant associations were observed with multiple previously identified AMD risk loci and 2 novel genes: HGS (peak SNP rs8070488, MAF 0.23, OR 0.91, p 7.52 = 10 x 5), which plays a role in the clathrin-mediated endocytosis signaling pathway, and TNF (peak SNP rs2071590, MAF 0.34, OR 0.89, p 1.17 = 10 x 5), which is a member of the atherosclerosis signaling and the LXR/ RXR activation pathways. Our results suggest that AMD and AD share genetic mechanisms.

• 出版日期2014-6