Journal Article

Sex differences in the genetic architecture of depression

Yoon, Jin-Sang, Kang, Hee-Ju, Shin, Il-Seon, Kim, Ju Han, Kim, Ki-Tae, Kim, Eun-Song, Kim, Sung-Wan, Park, Yoomi, Kim, Ju-Wan, Kim, Jae-Min, Yoo, Kyung-Hun

2020

Overview

The prevalence and clinical characteristics of depressive disorders differ between women and men; however, the genetic contribution to sex differences in depressive disorders has not been elucidated. To evaluate sex-specific differences in the genetic architecture of depression, whole exome sequencing of samples from 1000 patients (70.7% female) with depressive disorder was conducted. Control data from healthy individuals with no psychiatric disorder (n = 72, 26.4% female) and East-Asian subpopulation 1000 Genome Project data (n = 207, 50.7% female) were included. The genetic variation between men and women was directly compared using both qualitative and quantitative research designs. Qualitative analysis identified five genetic markers potentially associated with increased risk of depressive disorder in females, including three variants (rs201432982 within PDE4A , and rs62640397 and rs79442975 within FDX1L ) mapping to chromosome 19p13.2 and two novel variants (rs820182 and rs820148) within MYO15B at the chromosome 17p25.1 locus. Depressed patients homozygous for these variants showed more severe depressive symptoms and higher suicidality than those who were not homozygotes (i.e., heterozygotes and homozygotes for the non-associated allele). Quantitative analysis demonstrated that the genetic burden of protein-truncating and deleterious variants was higher in males than females, even after permutation testing. Our study provides novel genetic evidence that the higher prevalence of depressive disorders in women may be attributable to inherited variants.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/1647/2217 / 692/53/2421 / 692/699/476/1414 / Chromosome 17 / Chromosome 19 / Depressive Disorder - genetics / Depressive Disorder - pathology / Female / Females / Gender differences / Gene mapping / Genetic analysis / Genetic diversity / Genetic markers / Genetic Markers - genetics / Genetic Predisposition to Disease / Genomes / Heterozygotes / Homozygotes / Humanities and Social Sciences / Humans / Male / Mental depression / Mental disorders / Middle Aged / multidisciplinary / Polymorphism, Single Nucleotide / Qualitative analysis / Quantitative research / Science / Science (multidisciplinary) / Sex Characteristics / Sex differences / Whole Exome Sequencing - methods / Women