title: 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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK. Electronic address: Y.Zeng-6@sms.ed.ac.uk.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Pau
authors.initials: P
authors.lastname: Navarro
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Charley
authors.initials: C
authors.lastname: Xia
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Carmen
authors.initials: C
authors.lastname: Amador
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Fernandez-Pujals
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Pippa A
authors.initials: PA
authors.lastname: Thomson
authors.affiliation: Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
authors.forename: Archie
authors.initials: A
authors.lastname: Campbell
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Reka
authors.initials: R
authors.lastname: Nagy
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: Toni-Kim
authors.initials: TK
authors.lastname: Clarke
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Hafferty
authors.affiliation: Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK; Division of Population Health Sciences, University of Dundee, Dundee, UK.
authors.forename: Blair H
authors.initials: BH
authors.lastname: Smith
authors.affiliation: Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK; Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Lynne J
authors.initials: LJ
authors.lastname: Hocking
authors.affiliation: Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK; Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Sandosh
authors.initials: S
authors.lastname: Padmanabhan
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: MacIntyre
authors.affiliation: Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK; The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, UK.
authors.forename: Chris S
authors.initials: CS
authors.lastname: Haley
authors.affiliation: Division of Psychiatry, University of Edinburgh, Edinburgh, UK; Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McIntosh
mesh_terms: D003863:Depression / Q000453:epidemiology* / Q000209:etiology*; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000209:etiology; D004777:Environment; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D015233:Models, Statistical; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D057566:Self Report
keywords: Couple effect; Family environment; Linear mixed modeling; Major depressive disorder; SNP heritability; Self-declared depression