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

doi:10.1016/j.ebiom.2016.11.003

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

School of Medicine, Medical Sciences & Nutrition

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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.

Original language	English
Pages (from-to)	161-167
Number of pages	7
Journal	EBioMedicine
Volume	14
Early online date	4 Nov 2016
DOIs	https://doi.org/10.1016/j.ebiom.2016.11.003
Publication status	Published - 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.

Keywords

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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Shared Genetics and Couple-Associated Environment Are Major
© 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Final published version, 519 KBLicence: CC BY

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Zeng, Y., Navarro, P., Xia, C., Amador, C., Fernandez-Pujals, A. M., Thomson, P. A., Campbell, A., Nagy, R., Clarke, T.-K., Hafferty, J. D., Smith, B. H., Hocking, L. J., Padmanabhan, S., Hayward, C., MacIntyre, D. J., Porteous, D. J., Haley, C. S., & McIntosh, A. M. (2016). Shared Genetics and Couple-Associated Environment Are Major Contributors to the Risk of Both Clinical and Self-Declared Depression. EBioMedicine, 14, 161-167. https://doi.org/10.1016/j.ebiom.2016.11.003

Zeng, Y, Navarro, P, Xia, C, Amador, C, Fernandez-Pujals, AM, Thomson, PA, Campbell, A, Nagy, R, Clarke, T-K, Hafferty, JD, Smith, BH, Hocking, LJ, Padmanabhan, S, Hayward, C, MacIntyre, DJ, Porteous, DJ, Haley, CS & McIntosh, AM 2016, 'Shared Genetics and Couple-Associated Environment Are Major Contributors to the Risk of Both Clinical and Self-Declared Depression', EBioMedicine, vol. 14, pp. 161-167. https://doi.org/10.1016/j.ebiom.2016.11.003

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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).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.",

keywords = "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",

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

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.",

year = "2016",

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doi = "10.1016/j.ebiom.2016.11.003",

language = "English",

volume = "14",

pages = "161--167",

journal = "EBioMedicine",

issn = "2352-3964",

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TY - JOUR

T1 - Shared Genetics and Couple-Associated Environment Are Major Contributors to the Risk of Both Clinical and Self-Declared Depression

AU - Zeng, Yanni

AU - Navarro, Pau

AU - Xia, Charley

AU - Amador, Carmen

AU - Fernandez-Pujals, Ana M

AU - Thomson, Pippa A

AU - Campbell, Archie

AU - Nagy, Reka

AU - Clarke, Toni-Kim

AU - Hafferty, Jonathan D

AU - Smith, Blair H

AU - Hocking, Lynne J

AU - Padmanabhan, Sandosh

AU - Hayward, Caroline

AU - MacIntyre, Donald J

AU - Porteous, David J

AU - Haley, Chris S

AU - McIntosh, Andrew M

N1 - 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.

PY - 2016/12

Y1 - 2016/12

N2 - 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.

AB - 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.

KW - Depression

KW - Depressive Disorder, Major

KW - Environment

KW - Female

KW - Gene-Environment Interaction

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Male

KW - Models, Statistical

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Risk

KW - Self Report

KW - Journal Article

U2 - 10.1016/j.ebiom.2016.11.003

DO - 10.1016/j.ebiom.2016.11.003

M3 - Article

C2 - 27838479

SN - 2352-3964

VL - 14

SP - 161

EP - 167

JO - EBioMedicine

JF - EBioMedicine

ER -

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

Abstract

Bibliographical note

Keywords

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