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

Background: Both genetic and environmental factors contribute to risk of depression, but estimates of their rela- tive 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 as- sociated with genome-wide common genetic variants (SNP heritability), the additional pedigree-associated ge- netic 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 com- mon 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.