Genome-wide pleiotropy analysis of neuropathological traits related to Alzheimer's disease.
Alzheimer’s disease; ECRG4; Genome-wide association study; HDAC9; Neuropathological traits; Pleiotropy analysis
BACKGROUND: Simultaneous consideration of two neuropathological traits related to Alzheimer's disease (AD) has not been attempted in a genome-wide association study.
METHODS: We conducted genome-wide pleiotropy analyses using association summary statistics from the Beecham et al. study (PLoS Genet 10:e1004606, 2014) for AD-related neuropathological traits, including neuritic plaque (NP), neurofibrillary tangle (NFT), and cerebral amyloid angiopathy (CAA). Significant findings were further examined by expression quantitative trait locus and differentially expressed gene analyses in AD vs. control brains using gene expression data.
RESULTS: Genome-wide significant pleiotropic associations were observed for the joint model of NP and NFT (NP + NFT) with the single-nucleotide polymorphism (SNP) rs34487851 upstream of C2orf40 (alias ECRG4, P = 2.4 × 10
CONCLUSIONS: Our findings suggest that pleiotropy analysis is a useful approach to identifying novel genetic associations with complex diseases and their endophenotypes. Functional studies are needed to determine whether ECRG4 or HDAC9 is plausible as a therapeutic target.
Neurosciences (Brain & Spine)
Institute for Systems Biology
Chung, Jaeyoon; Zhang, Xiaoling; Allen, Mariet; Wang, Xue; Ma, Yiyi; Beecham, Gary; Montine, Thomas J; Younkin, Steven G; Dickson, Dennis W; Golde, Todd E; Price, Nathan D; Ertekin-Taner, Nilüfer; Lunetta, Kathryn L; Mez, Jesse; Mayeux, Richard; Haines, Jonathan L; Pericak-Vance, Margaret A; Schellenberg, Gerard; Jun, Gyungah R; and Farrer, Lindsay A, "Genome-wide pleiotropy analysis of neuropathological traits related to Alzheimer's disease." (2018). Journal Articles and Abstracts. 21.