Alternative Splicing Regulation of Low-Frequency Genetic Variants in Exon 2 of TREM2 in Alzheimer's Disease by Splicing-Based Aggregation.

ABSTRACT: TREM2 is among the most well-known Alzheimer's disease (AD) risk genes; however, the functional roles of its AD-associated variants remain to be elucidated, and most known risk alleles are low-frequency variants whose investigation is challenging. Here, we utilized a splicing-guided aggregation method in which multiple low-frequency TREM2 variants were bundled together to investigate the functional impact of those variants on alternative splicing in AD. We analyzed whole genome sequencing (WGS) and RNA-seq data generated from cognitively normal elderly controls (CN) and AD patients in two independent cohorts, representing three regions in the frontal lobe of the human brain: the dorsolateral prefrontal cortex (CN = 213 and AD = 376), frontal pole (CN = 72 and AD = 175), and i

SUBMITTER: Han S 

PROVIDER: S-EPMC8471326 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature