Exome-wide age-of-onset analysis reveals exonic variants in ERN1 and SPPL2C associated with Alzheimer's disease.

ABSTRACT: Despite recent discoveries in genome-wide association studies (GWAS) of genomic variants associated with Alzheimer's disease (AD), its underlying biological mechanisms are still elusive. The discovery of novel AD-associated genetic variants, particularly in coding regions and from APOE ε4 non-carriers, is critical for understanding the pathology of AD. In this study, we carried out an exome-wide association analysis of age-of-onset of AD with ~20,000 subjects and placed more emphasis on APOE ε4 non-carriers. Using Cox mixed-effects models, we find that age-of-onset shows a stronger genetic signal than AD case-control status, capturing many known variants with stronger significance, and also revealing new variants. We identified two novel variants, rs56201815, a rare synonymous variant in E

SUBMITTER: He L 

PROVIDER: S-EPMC7910483 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature