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

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, David J Porteous, Chris S Haley, Andrew M McIntosh

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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.

Original languageEnglish
Pages (from-to)161-167
Number of pages7
Early online date4 Nov 2016
Publication statusPublished - Dec 2016

Bibliographical note

This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/14/Z. GS:SFHS was funded by a grant from the Scottish Government Health Department, Chief Scientist Office, number CZD/16/6. The authors acknowledge with gratitude the financial support received for this work from the Dr. Mortimer and Theresa Sackler Foundation. PAT, DJP and AMM are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged by PN and CSH (BB/J004235/1). DJM is an NRS Fellow, funded by the CSO.


  • Depression
  • Depressive Disorder, Major
  • Environment
  • Female
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Models, Statistical
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Risk
  • Self Report
  • Journal Article


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