Dataset Information

Genetic stratification of depression by neuroticism: revisiting a diagnostic tradition.

ABSTRACT:

Background

Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.

Methods

We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.

Results

We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.

Conclusion

Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.

SUBMITTER: Adams MJ

PROVIDER: S-EPMC7737042 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic stratification of depression by neuroticism: revisiting a diagnostic tradition.

Adams Mark J MJ Howard David M DM Luciano Michelle M Clarke Toni-Kim TK Davies Gail G Hill W David WD Smith Daniel D Deary Ian J IJ Porteous David J DJ McIntosh Andrew M AM

Psychological medicine 20191002 15

<h4>Background</h4>Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.<h4>Methods</h4>We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classi ...[more]

PMID: 31576797

Similar Datasets

Project description:Background: Stressful life events (SLEs) and neuroticism are risk factors for major depressive disorder (MDD). However, SLEs and neuroticism are heritable and genetic risk for SLEs is associated with risk for MDD. We sought to investigate the genetic and environmental contributions to SLEs in a family-based sample, and quantify genetic overlap with MDD and neuroticism. Methods: A subset of Generation Scotland: the Scottish Family Health Study (GS), consisting of 9618 individuals with information on MDD, past 6 month SLEs, neuroticism and genome-wide genotype data was used in the present study. We estimated the heritability of SLEs using GCTA software. The environmental contribution to SLEs was assessed by modelling familial, couple and sibling components. Using polygenic risk scores (PRS) and LD score regression (LDSC) we analysed the genetic overlap between MDD, neuroticism and SLEs. Results: Past 6-month life events were positively associated with lifetime MDD status (β=0.21, r 2=1.1%, p=2.5 x 10 -25) and neuroticism (β =0.13, r 2=1.9%, p=1.04 x 10 -37) at the phenotypic level. Common SNPs explained 8% of the phenotypic variance in personal life events (those directly affecting the individual) (S.E.=0.03, p= 9 x 10 -4). A significant effect of couple environment was detected accounting for 13% (S.E.=0.03, p=0.016) of the phenotypic variation in SLEs. PRS analyses found that reporting more SLEs was associated with a higher polygenic risk for MDD (β =0.05, r 2=0.3%, p=3 x 10 -5), but not a higher polygenic risk for neuroticism. LDSC showed a significant genetic correlation between SLEs and both MDD (r G=0.33, S.E.=0.08 ) and neuroticism (r G=0.15, S.E.=0.07). Conclusions: These findings suggest that SLEs should not be regarded solely as environmental risk factors for MDD as they are partially heritable and this heritability is shared with risk for MDD and neuroticism. Further work is needed to determine the causal direction and source of these associations.

Dataset Information

Genetic stratification of depression by neuroticism: revisiting a diagnostic tradition.

Background

Methods

Results

Conclusion

Publications

Genetic stratification of depression by neuroticism: revisiting a diagnostic tradition.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets