Abstract
Alzheimer’s Disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous. Here, we investigated the association between AD and both common variants and aggregates of rare coding and noncoding variants in 13,371 individuals of diverse ancestry with whole genome sequence (WGS) data. Pooled-population analyses identified genetic variants in or near
APOE, BIN1
, and
LINC00320
significantly associated with AD (p < 5×10
-8
). Population-specific analyses identified a haplotype on chromosome 14 including
PSEN1
associated with AD in Hispanics, further supported by aggregate testing of rare coding and noncoding variants in this region. Finally, we observed suggestive associations (p < 5×10
-5
) of aggregates of rare coding rare variants in
ABCA7
among non-Hispanic Whites (p=5.4×10
-6
), and rare noncoding variants in the promoter of
TOMM40
distinct of
APOE
in pooled-population analyses (p=7.2×10
-8
). Complementary pooled-population and population-specific analyses offered unique insights into the genetic architecture of AD.