Rare variant association study of veteran twin whole-genomes links severe depression with a nonsynonymous change in the neuronal gene BHLHE22.

ABSTRACT:

Objectives

Major Depressive Disorder (MDD) is a complex neuropsychiatric disease with known genetic associations, but without known links to rare variation in the human genome. Here we aim to identify rare genetic variants associated with MDD using deep whole-genome sequencing data in an independent population.

Methods

We report the sequencing of 1,688 whole genomes in a large sample of male-male Veteran twins. Depression status was classified based on a structured diagnostic interview according to DSM-III-R diagnostic criteria. Searching only rare variants in genomic regions from recent GWAS on MDD, we used the optimised sequence kernel association test and Fisher's Exact test to fine map loci associated with severe depression.

Results

Our analysis identified

SUBMITTER: Hupalo D 

PROVIDER: S-EPMC9148382 | biostudies-literature | 2022 Mar-Apr

REPOSITORIES: biostudies-literature