Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
30708398
TITLE
Quantifying between-cohort and between-sex genetic heterogeneity in major depressive disorder.
ABSTRACT
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.
DATE PUBLISHED
2019 Feb 01
HISTORY
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
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Trzaskowski M Trzaskowski Maciej M Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Mehta D Mehta Divya D School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia.
Peyrot WJ Peyrot Wouter J WJ Department of Psychiatry, Vrije Universiteit Medical Center and GGZ in Geest, Amsterdam, The Netherlands.
Hawkes D Hawkes David D AGRF, The University of Queensland, Brisbane, Queensland, Australia.
Davies D Davies Daniel D Department of Psychiatry, Behavioural and Clinical Neuroscience Institute and Developmental Psychiatry, Cambridge University, Cambridge, England, United Kingdom.
Howard DM Howard David M DM Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
Kemper KE Kemper Kathryn E KE Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Sidorenko J Sidorenko Julia J Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Maier R Maier Robert R Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Ripke S Ripke Stephan S Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, Germany.
Mattheisen M Mattheisen Manuel M iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
Baune BT Baune Bernhard T BT Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia.
Grabe HJ Grabe Hans J HJ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri.
Jones L Jones Lisa L Institute of Health & Society, University of Worcester, Worcester, United Kingdom.
Jones I Jones Ian I MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.
Madden PAF Madden Pamela A F PAF Department of Psychiatry, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri.
McIntosh AM McIntosh Andrew M AM Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
Breen G Breen Gerome G NIHR BRC for Mental Health, King's College London, London, United Kingdom.
Lewis CM Lewis Cathryn M CM Department of Medical and Molecular Genetics, King's College London, London, United Kingdom.
Børglum AD Børglum Anders D AD Department of Biomedicine and iSEQ-Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.
Sullivan PF Sullivan Patrick F PF Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Martin NG Martin Nicholas G NG Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Kendler KS Kendler Kenneth S KS Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia.
Levinson DF Levinson Douglas F DF Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.
Wray NR Wray Naomi R NR Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
INVESTIGATORS
JOURNAL
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
MEDLINE JOURNAL
MEDLINETA: Am J Med Genet B Neuropsychiatr Genet
COUNTRY: United States
ISSNLINKING: 1552-4841
NLMUNIQUEID: 101235742
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
1087889 National Health & Medical Research Council
1113400 National Health & Medical Research Council
1078901 National Health & Medical Research Council
GENERAL NOTE
KEYWORDS
KEYWORD
LD score regression
MDD
depression
genetic heterogeneity
sex differences
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's