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
28373689
TITLE
Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression.
ABSTRACT
The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.Molecular Psychiatry advance online publication, 4 April 2017; doi:10.1038/mp.2017.44.
DATE PUBLISHED
2017 Apr 04
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2016/08/22
revised 2017/01/23
accepted 2017/02/02
entrez 2017/04/05 06:00
pubmed 2017/04/05 06:00
medline 2017/04/05 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Culverhouse RC Culverhouse R C RC Department of Medicine and Division of Biostatistics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Saccone NL Saccone N L NL Department of Genetics and Division of Biostatistics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Horton AC Horton A C AC Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Ma Y Ma Y Y Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Anstey KJ Anstey K J KJ Centre for Research on Ageing, Health and Wellbeing, The Australian National University, Canberra, ACT, Australia.
Banaschewski T Banaschewski T T Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Burmeister M Burmeister M M Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
Cohen-Woods S Cohen-Woods S S School of Psychology, Faculty of Social and Behavioural Sciences, Flinders University, Adelaide, SA, Australia.
Etain B Etain B B INSERM, U1144, Paris, France.
Fisher HL Fisher H L HL Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Goldman N Goldman N N Office of Population Research, Princeton University, Princeton, NJ, USA.
Guillaume S Guillaume S S Department of Emergency Psychiatry and Acute Care, CHU Montpellier, Montpellier, France.
Horwood J Horwood J J Department of Psychological Medicine, University of Otago Christchurch, Christchurch, New Zealand.
Juhasz G Juhasz G G NAP-A-SE New Antidepressant Target Research Group, Semmelweis University, Budapest, Hungary.
Lester KJ Lester K J KJ School of Psychology, University of Sussex, Brighton, UK.
Mandelli L Mandelli L L Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
Middeldorp CM Middeldorp C M CM Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Olié E Olié E E Department of Emergency Psychiatry and Acute Care, CHU Montpellier, Montpellier, France.
Villafuerte S Villafuerte S S Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
Air TM Air T M TM Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
Araya R Araya R R Centre for Global Mental Health, London School of Hygiene and Tropical Medicine, London, UK.
Bowes L Bowes L L Department of Experimental Psychology, University of Oxford, Oxford, UK.
Burns R Burns R R Centre for Research on Ageing, Health and Wellbeing, The Australian National University, Canberra, ACT, Australia.
Byrne EM Byrne E M EM Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Coffey C Coffey C C Centre for Adolescent Health, Murdoch Childrens Research Institute, Melbourne, VIC, Australia.
Coventry WL Coventry W L WL Discipline of Psychology, University of New England, Armidale, NSW, Australia.
Gawronski KA Gawronski K A B KA Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Glei D Glei D D Center for Population and Health, Georgetown University, Washington, DC, USA.
Hatzimanolis A Hatzimanolis A A Neurobiology Research Institute, Theodor-Theohari Cozzika Foundation, Athens, Greece.
Hottenga JJ Hottenga J-J JJ EMGO+ Institute for Health and Care Research, VU Medical Center Amsterdam, Amsterdam, The Netherlands.
Jaussent I Jaussent I I INSERM U1061 Neuropsychiatry, Montpellier, France.
Jawahar C Jawahar C C Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
Jennen-Steinmetz C Jennen-Steinmetz C C Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Kramer JR Kramer J R JR Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Lajnef M Lajnef M M INSERM U955, Creteil, France.
Little K Little K K Department of Paediatrics and School of Psychological Sciences, University of Melbourne, Melbourne, VIC, Australia.
Zu Schwabedissen HM Zu Schwabedissen H M HM Biopharmacy, Department Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Nauck M Nauck M M Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
Nederhof E Nederhof E E University of Groningen, University Medical Center Groningen, Interdisciplinary Center Psychopathology and Emotion Regulation, Groningen, The Netherlands.
Petschner P Petschner P P MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.
Peyrot WJ Peyrot W J WJ Department of Psychiatry, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands.
Schwahn C Schwahn C C Department of Prosthetic Dentistry, Gerostomatology and Dental Materials, University Medicine Greifswald, Greifswald, Germany.
Sinnamon G Sinnamon G G Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
Stacey D Stacey D D Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
Tian Y Tian Y Y Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA.
Toben C Toben C C Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
Van der Auwera S Van der Auwera S S Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Wainwright N Wainwright N N Department of Public Health and Primary Care, School of Clinical Medicine, Cambridge, UK.
Wang JC Wang J-C JC Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Willemsen G Willemsen G G EMGO+ Institute for Health and Care Research, VU Medical Center Amsterdam, Amsterdam, The Netherlands.
Anderson IM Anderson I M IM Manchester Academic Health Sciences Centre, Manchester, UK.
Arolt V Arolt V V Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.
Åslund C Åslund C C Västmanland County Hospital Västerås, Västerås, Sweden.
Bagdy G Bagdy G G MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.
Baune BT Baune B T BT Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
Bellivier F Bellivier F F INSERM, U1144, Paris, France.
Boomsma DI Boomsma D I DI EMGO+ Institute for Health and Care Research, VU Medical Center Amsterdam, Amsterdam, The Netherlands.
Courtet P Courtet P P Department of Emergency Psychiatry and Acute Care, CHU Montpellier, Montpellier, France.
Dannlowski U Dannlowski U U Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.
de Geus EJ de Geus E J C EJ EMGO+ Institute for Health and Care Research, VU Medical Center Amsterdam, Amsterdam, The Netherlands.
Deakin JF Deakin J F W JF Manchester Academic Health Sciences Centre, Manchester, UK.
Easteal S Easteal S S John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
Eley T Eley T T King's College London, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
Fergusson DM Fergusson D M DM Department of Psychological Medicine, University of Otago Christchurch, Christchurch, New Zealand.
Goate AM Goate A M AM Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Gonda X Gonda X X Department of Psychiatry and Psychotherapy, Kutvolgyi Clinical Center, Semmelweis University, Budapest, Hungary.
Grabe HJ Grabe H J HJ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Holzman C Holzman C C Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA.
Johnson EO Johnson E O EO Fellow Program and Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, NC, USA.
Kennedy M Kennedy M M Department of Pathology, University of Otago Christchurch, Christchurch, New Zealand.
Laucht M Laucht M M Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Martin NG Martin N G NG Genetic Epidemiology, QIMR Berghofer, Brisbane, QLD, Australia.
Munafò MR Munafò M R MR UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK.
Nilsson KW Nilsson K W KW Västmanland County Hospital Västerås, Västerås, Sweden.
Oldehinkel AJ Oldehinkel A J AJ University of Groningen, University Medical Center Groningen, Interdisciplinary Center Psychopathology and Emotion Regulation, Groningen, The Netherlands.
Olsson CA Olsson C A CA Centre for Adolescent Health, Murdoch Childrens Research Institute, Melbourne, VIC, Australia.
Ormel J Ormel J J University of Groningen, University Medical Center Groningen, Interdisciplinary Center Psychopathology and Emotion Regulation, Groningen, The Netherlands.
Otte C Otte C C Charité Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie Campus Benjamin Franklin, Berlin, Germany.
Patton GC Patton G C GC Department of Paediatrics, Murdoch Childrens Research Institute, University of Melbourne, Melbourne, VIC, Australia.
Penninx BW Penninx B W J H BW Department of Psychiatry, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands.
Ritchie K Ritchie K K INSERM U1061 Neuropsychiatry, Montpellier, France.
Sarchiapone M Sarchiapone M M Department of Health Sciences, University of Molise, Campobasso, Italy.
Scheid JM Scheid J M JM Department of Psychiatry, Michigan State University, East Lansing, MI, USA.
Serretti A Serretti A A Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
Smit JH Smit J H JH Department of Psychiatry, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands.
Stefanis NC Stefanis N C NC Neurobiology Research Institute, Theodor-Theohari Cozzika Foundation, Athens, Greece.
Surtees PG Surtees P G PG Department of Public Health and Primary Care, School of Clinical Medicine, Cambridge, UK.
Völzke H Völzke H H Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Weinstein M Weinstein M M Center for Population and Health, Georgetown University, Washington, DC, USA.
Whooley M Whooley M M Veterans Affairs Health Care System and University of California, San Francisco, CA, USA.
Nurnberger JI Jr Nurnberger J I JI Institute of Psychiatric Research, Departments of Psychiatry and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Breslau N Breslau N N Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA.
Bierut LJ Bierut L J LJ Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2017
MONTH: Apr
DAY: 04
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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U10 AA008401 NIAAA NIH HHS United States
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