Missense and loss-of-function variants at GWAS loci in familial Alzheimer's disease.

ABSTRACT:

Background

Few rare variants have been identified in genetic loci from genome-wide association studies (GWAS) of Alzheimer's disease (AD), limiting understanding of mechanisms, risk assessment, and genetic counseling.

Methods

Using genome sequencing data from 197 families in the National Institute on Aging Alzheimer's Disease Family Based Study and 214 Caribbean Hispanic families, we searched for rare coding variants within known GWAS loci from the largest published study.

Results

Eighty-six rare missense or loss-of-function (LoF) variants completely segregated in 17.5% of families, but in 91 (22.1%) families Apolipoprotein E (APOE)-𝜀4 was the only variant segregating. However, in 60.3% of families, APOE 𝜀4, missense, and LoF variants were not found within the GWAS

SUBMITTER: Gunasekaran TI 

PROVIDER: S-EPMC11567820 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature