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PMID |
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TITLE |
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Quantifying between-cohort and between-sex genetic heterogeneity in major depressive disorder. |
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ABSTRACT |
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Major depressive disorder (MDD) is clinically heterogeneous with prevalence rates twice as high in women as in men. There are many possible sources of heterogeneity in MDD most of which are not measured in a sufficiently comparable way across study samples. Here, we assess genetic heterogeneity based on two fundamental measures, between-cohort and between-sex heterogeneity. First, we used genome-wide association study (GWAS) summary statistics to investigate between-cohort genetic heterogeneity using the 29 research cohorts of the Psychiatric Genomics Consortium (PGC; N cases = 16,823, N controls = 25,632) and found that some of the cohort heterogeneity can be attributed to ascertainment differences (such as recruitment of cases from hospital vs. community sources). Second, we evaluated between-sex genetic heterogeneity using GWAS summary statistics from the PGC, Kaiser Permanente GERA, UK Biobank, and the Danish iPSYCH studies but did not find convincing evidence for genetic differences between the sexes. We conclude that there is no evidence that the heterogeneity between MDD data sets and between sexes reflects genetic heterogeneity. Larger sample sizes with detailed phenotypic records and genomic data remain the key to overcome heterogeneity inherent in assessment of MDD. |
© 2019 Wiley Periodicals, Inc. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
received |
2018/09/05 |
revised |
2018/11/19 |
accepted |
2019/01/04 |
entrez |
2019/02/02 06:00 |
pubmed |
2019/02/02 06:00 |
medline |
2019/02/02 06:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Trzaskowski M |
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Trzaskowski |
Maciej |
M |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. |
Mehta D |
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Mehta |
Divya |
D |
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School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia. |
Peyrot WJ |
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Peyrot |
Wouter J |
WJ |
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Department of Psychiatry, Vrije Universiteit Medical Center and GGZ in Geest, Amsterdam, The Netherlands. |
Hawkes D |
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Hawkes |
David |
D |
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AGRF, The University of Queensland, Brisbane, Queensland, Australia. |
Davies D |
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Davies |
Daniel |
D |
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Department of Psychiatry, Behavioural and Clinical Neuroscience Institute and Developmental Psychiatry, Cambridge University, Cambridge, England, United Kingdom. |
Howard DM |
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Howard |
David M |
DM |
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Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom. |
Kemper KE |
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Kemper |
Kathryn E |
KE |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. |
Sidorenko J |
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Sidorenko |
Julia |
J |
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Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. |
Maier R |
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Maier |
Robert |
R |
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Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. |
Ripke S |
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Ripke |
Stephan |
S |
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Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, Germany. |
Mattheisen M |
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Mattheisen |
Manuel |
M |
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iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark. |
Baune BT |
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Baune |
Bernhard T |
BT |
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Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia. |
Grabe HJ |
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Grabe |
Hans J |
HJ |
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Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. |
Heath AC |
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Heath |
Andrew C |
AC |
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Department of Psychiatry, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri. |
Jones L |
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Jones |
Lisa |
L |
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Institute of Health & Society, University of Worcester, Worcester, United Kingdom. |
Jones I |
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Jones |
Ian |
I |
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MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom. |
Madden PAF |
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Madden |
Pamela A F |
PAF |
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Department of Psychiatry, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri. |
McIntosh AM |
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McIntosh |
Andrew M |
AM |
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Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom. |
Breen G |
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Breen |
Gerome |
G |
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NIHR BRC for Mental Health, King's College London, London, United Kingdom. |
Lewis CM |
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Lewis |
Cathryn M |
CM |
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Department of Medical and Molecular Genetics, King's College London, London, United Kingdom. |
Børglum AD |
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Børglum |
Anders D |
AD |
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Department of Biomedicine and iSEQ-Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark. |
Sullivan PF |
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Sullivan |
Patrick F |
PF |
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Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. |
Martin NG |
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Martin |
Nicholas G |
NG |
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Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
Kendler KS |
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Kendler |
Kenneth S |
KS |
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Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia. |
Levinson DF |
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Levinson |
Douglas F |
DF |
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Psychiatry and Behavioral Sciences, Stanford University, Stanford, California. |
Wray NR |
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Wray |
Naomi R |
NR |
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Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia. |
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Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: |
ISSUE: |
TITLE: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics |
ISOABBREVIATION: Am. J. Med. Genet. B Neuropsychiatr. Genet. |
YEAR: 2019 |
MONTH: Feb |
DAY: 01 |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 1552-485X |
ISSNTYPE: Electronic |
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MEDLINE JOURNAL |
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MEDLINETA: Am J Med Genet B Neuropsychiatr Genet |
COUNTRY: United States |
ISSNLINKING: 1552-4841 |
NLMUNIQUEID: 101235742 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
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COMMENTS AND CORRECTIONS |
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GRANTS |
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GRANTID |
AGENCY |
COUNTRY |
1087889 |
National Health & Medical Research Council |
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1113400 |
National Health & Medical Research Council |
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1078901 |
National Health & Medical Research Council |
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GENERAL NOTE |
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KEYWORDS |
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KEYWORD |
LD score regression |
MDD |
depression |
genetic heterogeneity |
sex differences |
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MESH HEADINGS |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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OTHER ID's |
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