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Shared genetics and couple-associated environment are major contributors to the risk of both clinical and self-declared depression

By Yanni Zeng, Pau Navarro, Charley Xia, Carmen Amador, Ana M Fernandez-Pujals, Pippa A. Thomson, Archie Campbell, Reka Nagy, Toni-Kim Clarke, Jonathan D. Hafferty, Blair H Smith, Lynne J. Hocking, Sandosh Padmanabhan, Caroline Hayward, Donald J MacIntyre, Professor D Porteous, Chris S Haley, Andrew M McIntosh

Posted 21 Sep 2016
bioRxiv DOI: 10.1101/076398 (published DOI: 10.1016/j.ebiom.2016.11.003)

Background: both genetic and environmental contributions to risk of depression have been identified, but estimates of their effects are limited. Commonalities between major depressive disorder (MDD) and self-declared depression (SDD) are also unclear. Dissecting the genetic and environmental contributions to these traits and their correlation would inform the design and interpretation of genetic studies. Methods: using data from a large Scottish family-based cohort (GS:SFHS, N=21,387), we estimated the genetic and environmental contributions to MDD and SDD. Genetic effects associated with common genome-wide genetic variants (SNP heritability) and additional pedigree-associated genetic variation and Non-genetic effects associated with common environments were estimated using linear mixed modeling (LMM). Findings: Both MDD and SDD had significant contributions from effects of common genetic variants, the additional genetic effect of the pedigree and the common environmental effect shared by couples. The correlation between SDD and MDD was high (r=1.00, se=0.21) for common-variant-associated genetic effects and moderate for both the additional genetic effect of the pedigree (r=0.58, se=0.08) and the couple-shared environmental effect (r=0.53, se=0.22). Interpretation: Both genetics and couple-shared environmental effects were the 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.

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