GWAS on family history of Alzheimer’s disease

• DOI: 10.1038/s41398-018-0150-6
• Publication Date: 2018-05-18T13:38:46Z
• Authors: Riccardo E. Marioni; Sarah E. Harris; Qian Zhang; Allan F. McRae; Saskia P. Hagenaars; W. David Hill; Gail Davies; Craig W. Ritchie; Catharine R. Gale; John M. Starr; Alison M. Goate; David J. Porteous; Jian Yang; Kathryn L. Evans; Ian J. Deary; Naomi R. Wray; Peter M. Visscher
• Keywords: Genome-wide Association Study

Alzheimer's disease (AD) is a public health priority for the 21st century. Risk reduction currently revolves around lifestyle changes with much research trying to elucidate biological underpinnings. We show that self-report of parental history dementia case ascertainment in genome-wide association study 314,278 participants from UK Biobank (27,696 maternal cases, 14,338 paternal cases) valid proxy an AD genetic study. After meta-analysing published consortium data (n = 74,046 25,580 cases across discovery and replication analyses), three new AD-associated loci (P < 5 × 10-8) are identified. These contain genes relevant neurodegeneration: ADAM10, BCKDK/KAT8 ACE. Novel gene-based include drug targets such as VKORC1 (warfarin dose). report evidence SNPs TOMM40 gene potentially mediated by both expression DNA methylation prefrontal cortex. However, it likely multiple variants affecting trait methylation/expression. Our discovered may help mechanisms underlying and, they other diseases disorders, warrant further exploration potential precision medicine applications.