A rare missense variant of CASP7 is associated with familial late‐onset Alzheimer's disease

• DOI: 10.1016/j.jalz.2018.10.005
• Publication Date: 2019-01-03T17:11:43Z
• Authors: Xiaoling Zhang; Congcong Zhu; Gary Beecham; Badri N. Vardarajan; Yiyi Ma; Daniel Lancour; John J. Farrell; Jaeyoon Chung; ; Richard Mayeux; Jonathan Haines; Gerard Schellenberg; Margaret Pericak‐...; Kathy Lunetta; Lindsay Farrer
• Keywords: Genetic Association; Genome-wide Association Study

Abstract Introduction The genetic architecture of Alzheimer's disease (AD) is only partially understood. Methods We conducted an association study for AD using whole sequence data from 507 genetically enriched cases (i.e., having close relatives affected by AD) and 4917 cognitively healthy controls European ancestry (EA) 172 179 Caribbean Hispanic ancestry. Confirmation top findings stage 1 was sought in two family‐based genome‐wide sets a genome–sequencing set comprising members 42 EA 115 families. Results identified associations EAs with variants 12 novel loci. most robust finding rare CASP7 missense variant (rs116437863; P = 2.44 × 10 −10 ) which improved when combined results 2 ( 1.92 ). Discussion Our demonstrated that case design can strengthen signals, thus allowing detection would otherwise be missed traditional case‐control study.