African Ancestry GWAS of Dementia in a Large Military Cohort Identifies Significant Risk Loci

We 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.