Author:
Sherva Richard,Zhang Rui,Sahelijo Nathan,Jun Gyungah,Anglin Tori,Chanfreau Catherine,Cho Kelly,Fonda Jennifer R.,Gaziano J. Michael,Harrington Kelly M.,Ho Yuk-Lam,Kremen William,Litkowski Elizabeth,Lynch Julie,Neale Zoe,Roussos Panos,Marra David,Mez Jesse,Miller Mark W.,Salat David H.,Tsuang Debby,Wolf Erika,Zeng Qing,Panizzon Matthew S.,Merritt Victoria C.,Farrer Lindsay A.,Hauger Richard L.,Logue Mark W.
Abstract
AbstractWe conducted the largest genome-wide association study (GWAS) of Alzheimer’s disease and related dementia (ADRD) in individuals of African-ancestry (AFR) to date using participants from the Million Veteran Program (MVP; 4,012 ADRD cases and 18,435 controls). A proxy GWAS based on survey-reported parental dementia (n=6,641 proxy cases, 45,970 controls) was also performed. The MVP AFR ADRD GWAS and proxy GWAS results were meta-analyzed and combined with the Alzheimer’s Disease Genetics Consortium’s (ADGC) AFR AD GWAS results. The MVP meta-analysis yielded genome-wide significant associations in or near APOE, ROBO1, and RP11-340A13.2. The MVP/ADGC meta-analysis yielded additional genome-wide significant variants near known risk genes TREM2, CD2AP, and ABCA7. We examined differences in expression of the implicated genes in a cohort of AD case and control brains. This study provides insight into dementia pathophysiology in historically understudied individuals of AFR and may help to address health disparities.
Publisher
Cold Spring Harbor Laboratory