Functional genomic analysis delineates regulatory mechanisms of GWAS-identified bipolar disorder risk variants.

ABSTRACT:

Background

Genome-wide association studies (GWASs) have identified multiple risk loci for bipolar disorder (BD). However, pinpointing functional (or causal) variants in the reported risk loci and elucidating their regulatory mechanisms remain challenging.

Methods

We first integrated chromatin immunoprecipitation sequencing (ChIP-Seq) data from human brain tissues (or neuronal cell lines) and position weight matrix (PWM) data to identify functional single-nucleotide polymorphisms (SNPs). Then, we verified the regulatory effects of these transcription factor (TF) binding-disrupting SNPs (hereafter referred to as "functional SNPs") through a series of experiments, including reporter gene assays, allele-specific expression (ASE) analysis, TF knockdown, CRISPR/Cas9-mediated genom

SUBMITTER: Chen R 

PROVIDER: S-EPMC9121601 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature