Dataset Information

Shared Genetics and Couple-Associated Environment Are Major Contributors to the Risk of Both Clinical and Self-Declared Depression.

ABSTRACT:

Background

Both genetic and environmental factors contribute to risk of depression, but estimates of their relative contributions are limited. Commonalities between clinically-assessed major depressive disorder (MDD) and self-declared depression (SDD) are also unclear.

Methods

Using data from a large Scottish family-based cohort (GS:SFHS, N=19,994), we estimated the genetic and environmental variance components for MDD and SDD. The components representing the genetic effect associated with genome-wide common genetic variants (SNP heritability), the additional pedigree-associated genetic effect and non-genetic effects associated with common environments were estimated in a linear mixed model (LMM).

Findings

Both MDD and SDD had significant contributions from components representing the effect from common genetic variants, the additional genetic effect associated with the pedigree and the common environmental effect shared by couples. The estimate of correlation between SDD and MDD was high (r=1.00, se=0.20) for common-variant-associated genetic effect and lower for the additional genetic effect from the pedigree (r=0.57, se=0.08) and the couple-shared environmental effect (r=0.53, se=0.22).

Interpretation

Both genetics and couple-shared environmental effects were major factors influencing liability to depression. SDD may provide a scalable alternative to MDD in studies seeking to identify common risk variants. Rarer variants and environmental effects may however differ substantially according to different definitions of depression.

SUBMITTER: Zeng Y

PROVIDER: S-EPMC5161419 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Publications

Shared Genetics and Couple-Associated Environment Are Major Contributors to the Risk of Both Clinical and Self-Declared Depression.

Zeng Yanni Y Navarro Pau P Xia Charley C Amador Carmen C Fernandez-Pujals Ana M AM Thomson Pippa A PA Campbell Archie A Nagy Reka R Clarke Toni-Kim TK Hafferty Jonathan D JD Smith Blair H BH Hocking Lynne J LJ Padmanabhan Sandosh S Hayward Caroline C MacIntyre Donald J DJ Porteous David J DJ Haley Chris S CS McIntosh Andrew M AM

EBioMedicine 20161104

<h4>Background</h4>Both genetic and environmental factors contribute to risk of depression, but estimates of their relative contributions are limited. Commonalities between clinically-assessed major depressive disorder (MDD) and self-declared depression (SDD) are also unclear.<h4>Methods</h4>Using data from a large Scottish family-based cohort (GS:SFHS, N=19,994), we estimated the genetic and environmental variance components for MDD and SDD. The components representing the genetic effect associ ...[more]

PMID: 27838479

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Project description:PurposeGlaucoma, a leading cause of blindness worldwide, is suspected to exhibit a notable association with psychological disturbances. This study aimed to investigate epidemiological associations and explore shared genetic architecture between glaucoma and mental traits, including depression and anxiety.MethodsMultivariable logistic regression and Cox proportional hazards regression models were employed to investigate longitudinal associations based on UK Biobank. A stepwise approach was used to explore the shared genetic architecture. First, linkage disequilibrium score regression inferred global genetic correlations. Second, MiXeR analysis quantified the number of shared causal variants. Third, specific shared loci were detected through conditional/conjunctional false discovery rate (condFDR/conjFDR) analysis and characterized for biological insights. Finally, two-sample Mendelian randomization (MR) was conducted to investigate bidirectional causal associations.ResultsGlaucoma was significantly associated with elevated risks of hospitalized depression (hazard ratio [HR] = 1.54; 95% confidence interval [CI], 1.01-2.34) and anxiety (HR = 2.61; 95% CI, 1.70-4.01) compared to healthy controls. Despite the absence of global genetic correlations, MiXeR analysis revealed 300 variants shared between glaucoma and depression, and 500 variants shared between glaucoma and anxiety. Subsequent condFDR/conjFDR analysis discovered 906 single-nucleotide polymorphisms (SNPs) jointly associated with glaucoma and depression and two associated with glaucoma and anxiety. The MR analysis did not support robust causal associations but indicated the existence of pleiotropic genetic variants influencing both glaucoma and depression.ConclusionsOur study enhances the existing epidemiological evidence and underscores the polygenic overlap between glaucoma and mental traits. This observation suggests a correlation shaped by pleiotropic genetic variants rather than being indicative of direct causal relationships.

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Dataset Information

Shared Genetics and Couple-Associated Environment Are Major Contributors to the Risk of Both Clinical and Self-Declared Depression.

Background

Methods

Findings

Interpretation

Publications

Shared Genetics and Couple-Associated Environment Are Major Contributors to the Risk of Both Clinical and Self-Declared Depression.

Similar Datasets

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