A transcriptome-wide association study of Alzheimer’s disease using prediction models of relevant tissues identifies novel candidate susceptibility genes

Autor: Yanfa Sun, Jingjing Zhu, Dan Zhou, Saranya Canchi, Chong Wu, Nancy J. Cox, Robert A. Rissman, Eric R. Gamazon, Lang Wu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Genome Medicine, Vol 13, Iss 1, Pp 1-11 (2021)
Druh dokumentu: article
ISSN: 1756-994X
DOI: 10.1186/s13073-021-00959-y
Popis: Abstract Background Genome-wide association studies (GWAS) have identified over 56 susceptibility loci associated with Alzheimer’s disease (AD), but the genes responsible for these associations remain largely unknown. Methods We performed a large transcriptome-wide association study (TWAS) leveraging modified UTMOST (Unified Test for MOlecular SignaTures) prediction models of ten brain tissues that are potentially related to AD to discover novel AD genetic loci and putative target genes in 71,880 (proxy) cases and 383,378 (proxy) controls of European ancestry. Results We identified 53 genes with predicted expression associations with AD risk at Bonferroni correction threshold (P value < 3.38 × 10−6). Based on fine-mapping analyses, 21 genes at nine loci showed strong support for being causal. Conclusions Our study provides new insights into the etiology and underlying genetic architecture of AD.
Databáze: Directory of Open Access Journals
Nepřihlášeným uživatelům se plný text nezobrazuje