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Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies

Published online by Cambridge University Press:  21 March 2016

A. Demirkan ,
J. Lahti ,
N. Direk ,
A. Viktorin ,
K. L. Lunetta ,
A. Terracciano ,
M. A. Nalls ,
T. Tanaka ,
K. Hek  and
M. Fornage
...Show all authors
A. Demirkan
Affiliation:
Genetic Epidemiology Unit, Departments of Epidemiology and Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
J. Lahti*
Affiliation:
Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland
N. Direk
Affiliation:
Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
A. Viktorin
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
K. L. Lunetta
Affiliation:
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
A. Terracciano
Affiliation:
National Institute on Aging, National Institutes of Health, Baltimore, MD, USA College of Medicine, Florida State University, Tallahassee, FL, USA
M. A. Nalls
Affiliation:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
T. Tanaka
Affiliation:
National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
K. Hek
Affiliation:
Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands Department of Psychiatry, Epidemiological and Social Psychiatric Research Institute, Erasmus MC, Rotterdam, The Netherlands
M. Fornage
Affiliation:
Houston Institute of Molecular Medicine, University of Texas, Houston, TX, USA
J. Wellmann
Affiliation:
Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany
M. C. Cornelis
Affiliation:
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
H. M. Ollila
Affiliation:
Public Health Genomics Unit and Institute for Molecular Medicine Finland (FIMM), National Institute for Health and Welfare, Helsinki, Finland
L. Yu
Affiliation:
Department of Neurological Sciences, Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA
J. A. Smith
Affiliation:
Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA
L. C. Pilling
Affiliation:
University of Exeter Medical School, Exeter, UK
A. Isaacs
Affiliation:
Genetic Epidemiology Unit, Departments of Epidemiology and Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
A. Palotie
Affiliation:
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
W. V. Zhuang
Affiliation:
Department of Preventive Medicine and Public Health, School of Medicine, Creighton University, Omaha, NE, USA
A. Zonderman
Affiliation:
National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
J. D. Faul
Affiliation:
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA
A. Sutin
Affiliation:
National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
O. Meirelles
Affiliation:
National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
A. Mulas
Affiliation:
Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy
A. Hofman
Affiliation:
Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
A. Uitterlinden
Affiliation:
Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands Member of Netherlands Consortium for Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
F. Rivadeneira
Affiliation:
Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands Member of Netherlands Consortium for Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
M. Perola
Affiliation:
Public Health Genomics Unit and Institute for Molecular Medicine Finland (FIMM), National Institute for Health and Welfare, Helsinki, Finland
W. Zhao
Affiliation:
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA
V. Salomaa
Affiliation:
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
K. Yaffe
Affiliation:
Departments of Psychiatry, University of California, San Francisco, CA, USA
A. I. Luik
Affiliation:
Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
Y. Liu
Affiliation:
Center for Human Genomics, Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA
J. Ding
Affiliation:
Geriatrics & Gerontology, Sticht Center on Aging, Wake Forest University, Primate Center, Epidemiology & Prevention, Winston-Salem, NC, USA
P. Lichtenstein
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
M. Landén
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
E. Widen
Affiliation:
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
D. R. Weir
Affiliation:
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA
D. J. Llewellyn
Affiliation:
University of Exeter Medical School, Exeter, UK
A. Murray
Affiliation:
University of Exeter Medical School, Exeter, UK
S. L. R. Kardia
Affiliation:
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA
J. G. Eriksson
Affiliation:
National Institute for Health and Welfare, Helsinki, Finland Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
K. Koenen
Affiliation:
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
P. K. E. Magnusson
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
L. Ferrucci
Affiliation:
National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
T. H. Mosley
Affiliation:
Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
F. Cucca
Affiliation:
Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy
B. A. Oostra
Affiliation:
Genetic Epidemiology Unit, Departments of Epidemiology and Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands
D. A. Bennett
Affiliation:
Department of Neurological Sciences, Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA
T. Paunio
Affiliation:
Public Health Genomics Unit and Institute for Molecular Medicine Finland (FIMM), National Institute for Health and Welfare, Helsinki, Finland
K. Berger
Affiliation:
Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany
T. B. Harris
Affiliation:
Laboratory of Epidemiology, Demography, and Biometry, National Institute on Ageing, National Institutes of Health, Bethesda, MD, USA
N. L. Pedersen
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
J. M. Murabito
Affiliation:
Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine, Boston, MA, USA
H. Tiemeier
Affiliation:
Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
C. M. van Duijn
Affiliation:
Genetic Epidemiology Unit, Departments of Epidemiology and Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands Member of Netherlands Consortium for Healthy Aging sponsored by Netherlands Genomics Initiative, Leiden, The Netherlands
K. Räikkönen
Affiliation:
Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland
NABEC
Affiliation:
North American Brain Expression Consortium, USA
UKBEC
Affiliation:
UK Brain Expression Consortium, UK
*
*Address for correspondence: J. Lahti, Institute of Behavioural Sciences, University of Helsinki, Siltavuorenpenger 1A, 00014 Helsingin yliopisto, Finland. (Email: [email protected])
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Abstract

Background

Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.

Method

We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).

Results

One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.

Conclusions

Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

Keywords

Genome-wide association studiesmajor depressive disordermeta-analyses
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 8 , June 2016 , pp. 1613 - 1623
Copyright
Copyright © Cambridge University Press 2016 

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