Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals

Margarita Rivera¹, Adam E Locke², Tanguy Corre², Darina Czamara², Christiane Wolf², Ana Ching-Lopez², Yuri Milaneschi², Stefan Kloiber², Sarah Cohen-Woods², James Rucker², Katherine J Aitchison², Sven Bergmann², Dorret I Boomsma², Nick Craddock², Michael Gill², Florian Holsboer², Jouke-Jan Hottenga², Ania Korszun², Zoltan Kutalik², Susanne Lucae², Wolfgang Maier², Ole Mors², Bertram Müller-Myhsok², Michael J Owen², Brenda W J H Penninx², Martin Preisig², John Rice², Marcella Rietschel², Federica Tozzi², Rudolf Uher², Peter Vollenweider², Gerard Waeber², Gonneke Willemsen², Ian W Craig², Anne E Farmer², Cathryn M Lewis², Gerome Breen², Peter McGuffin²

Affiliations

¹ Margarita Rivera, PhD, Department of Biochemistry and Molecular Biology II and Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain, and MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, Kinǵs College London, UK; Adam E. Locke, PhD, Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA; Tanguy Corre, PhD, Department of Medical Genetics, University of Lausanne, Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland; Darina Czamara, PhD, Christiane Wolf, PhD, Max Planck Institute of Psychiatry, Munich, Germany; Ana Ching-Lopez, Department of Psychiatry, School of Medicine, University of Granada, and Institute of Neurosciences Federico Olóriz, Centra de Investigación Biomédica, University of Granada, Spain; Yuri Milaneschi, PhD, Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center/GGZ in Geest, Amsterdam, The Netherlands; Stefan Kloiber, MD, Max Planck Institute of Psychiatry, Munich, Germany; Sara Cohen-Woods, PhD, School of Psychology, Flinders University, Adelaide, South Australia, Australia; James Rucker, MD, PhD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Katherine J. Aitchison, MD, PhD, Department of Psychiatry, University of Alberta, Alberta, Canada; Sven Bergmann, PhD, Department of Medical Genetics, University of Lausanne, Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland; Dorret I. Boomsma, PhD, Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands; Nick Craddock, MB, PhD, FMedSci, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Henry Wellcome Building, Cardiff, UK; Michael Gill, MD, Department of Psychiatry, Trinity Centre for Health Sciences, Dublin 8, Ireland; Florian Holsboer, MD, PhD, Max Planck Institute of Psychiatry, Munich, Germany; Jouke-Jan Hottenga, PhD, Department of Psychiatry, University of Alberta, Alberta, Canada; Ania Korszun, PhD, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Zoltan Kutalik, PhD, Department of Medical Genetics, University of Lausanne, Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland; Susanne Lucae, MD, PhD, Max Planck Institute of Psychiatry, Munich, Germany; Wolfgang Maier, MD, Department of Psychiatry, University of Bonn, Bonn, Germany; Ole Mors, MD, PhD, Research Department P, Aarhus University Hospital, Risskov, Denmark; Bertram Müller-Myhsok MD, Max Planck Institute of Psychiatry, Munich, Germany; Michael J. Owen, MB, PhD, FMedSci, MRC Centre for Neuropsychiatry Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK; Brenda W. J. H. Penninx, PhD, Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center/GGZ in Geest, Amsterdam, The Netherlands; Martin Preisig, MD, Department of Psychiatry, Lausanne University Hospital, 1008 Prilly-Lausanne, Switzerland; John Rice, PhD, Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA; Marcella Rietschel, MD, Central Institute of Mental Health, Mannheim, Germany; Federica Tozzi, MD, Genetics Division, Drug Discovery, GlaxoSmithKline Research and Development, Verona, Italy; Rudolf Uher, MD, PhD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK, and Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada; Peter Vollenweider, MD, PhD, Gerard Waeber, MD, PhD, Division of Internal Medicine, CHUV, Lausanne, Switzerland; Gonneke Willemsen, PhD, Department of Psychiatry, University of Alberta, Alberta, Canada; Ian W. Craig, PhD, Anne E. Farmer, MD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Cathryn M. Lewis, PhD, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, and Department of Medical and Molecular Genetics, School of Medicine, King's College London, UK; Gerome Breen, PhD, Peter McGuffin, MB, PhD, FMedSci, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK margarita.rivera_sanchez@kcl.ac.uk.
² Margarita Rivera, PhD, Department of Biochemistry and Molecular Biology II and Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain, and MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, Kinǵs College London, UK; Adam E. Locke, PhD, Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA; Tanguy Corre, PhD, Department of Medical Genetics, University of Lausanne, Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland; Darina Czamara, PhD, Christiane Wolf, PhD, Max Planck Institute of Psychiatry, Munich, Germany; Ana Ching-Lopez, Department of Psychiatry, School of Medicine, University of Granada, and Institute of Neurosciences Federico Olóriz, Centra de Investigación Biomédica, University of Granada, Spain; Yuri Milaneschi, PhD, Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center/GGZ in Geest, Amsterdam, The Netherlands; Stefan Kloiber, MD, Max Planck Institute of Psychiatry, Munich, Germany; Sara Cohen-Woods, PhD, School of Psychology, Flinders University, Adelaide, South Australia, Australia; James Rucker, MD, PhD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Katherine J. Aitchison, MD, PhD, Department of Psychiatry, University of Alberta, Alberta, Canada; Sven Bergmann, PhD, Department of Medical Genetics, University of Lausanne, Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland; Dorret I. Boomsma, PhD, Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands; Nick Craddock, MB, PhD, FMedSci, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Henry Wellcome Building, Cardiff, UK; Michael Gill, MD, Department of Psychiatry, Trinity Centre for Health Sciences, Dublin 8, Ireland; Florian Holsboer, MD, PhD, Max Planck Institute of Psychiatry, Munich, Germany; Jouke-Jan Hottenga, PhD, Department of Psychiatry, University of Alberta, Alberta, Canada; Ania Korszun, PhD, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Zoltan Kutalik, PhD, Department of Medical Genetics, University of Lausanne, Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland; Susanne Lucae, MD, PhD, Max Planck Institute of Psychiatry, Munich, Germany; Wolfgang Maier, MD, Department of Psychiatry, University of Bonn, Bonn, Germany; Ole Mors, MD, PhD, Research Department P, Aarhus University Hospital, Risskov, Denmark; Bertram Müller-Myhsok MD, Max Planck Institute of Psychiatry, Munich, Germany; Michael J. Owen, MB, PhD, FMedSci, MRC Centre for Neuropsychiatry Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK; Brenda W. J. H. Penninx, PhD, Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center/GGZ in Geest, Amsterdam, The Netherlands; Martin Preisig, MD, Department of Psychiatry, Lausanne University Hospital, 1008 Prilly-Lausanne, Switzerland; John Rice, PhD, Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA; Marcella Rietschel, MD, Central Institute of Mental Health, Mannheim, Germany; Federica Tozzi, MD, Genetics Division, Drug Discovery, GlaxoSmithKline Research and Development, Verona, Italy; Rudolf Uher, MD, PhD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK, and Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada; Peter Vollenweider, MD, PhD, Gerard Waeber, MD, PhD, Division of Internal Medicine, CHUV, Lausanne, Switzerland; Gonneke Willemsen, PhD, Department of Psychiatry, University of Alberta, Alberta, Canada; Ian W. Craig, PhD, Anne E. Farmer, MD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Cathryn M. Lewis, PhD, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, and Department of Medical and Molecular Genetics, School of Medicine, King's College London, UK; Gerome Breen, PhD, Peter McGuffin, MB, PhD, FMedSci, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.

PMID: 28642257
PMCID: PMC5537566
DOI: 10.1192/bjp.bp.116.183475

Review

Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals

Margarita Rivera et al. Br J Psychiatry. 2017 Aug.

. 2017 Aug;211(2):70-76.

doi: 10.1192/bjp.bp.116.183475. Epub 2017 Jun 22.

Authors

Affiliations

¹ Margarita Rivera, PhD, Department of Biochemistry and Molecular Biology II and Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain, and MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, Kinǵs College London, UK; Adam E. Locke, PhD, Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA; Tanguy Corre, PhD, Department of Medical Genetics, University of Lausanne, Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland; Darina Czamara, PhD, Christiane Wolf, PhD, Max Planck Institute of Psychiatry, Munich, Germany; Ana Ching-Lopez, Department of Psychiatry, School of Medicine, University of Granada, and Institute of Neurosciences Federico Olóriz, Centra de Investigación Biomédica, University of Granada, Spain; Yuri Milaneschi, PhD, Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center/GGZ in Geest, Amsterdam, The Netherlands; Stefan Kloiber, MD, Max Planck Institute of Psychiatry, Munich, Germany; Sara Cohen-Woods, PhD, School of Psychology, Flinders University, Adelaide, South Australia, Australia; James Rucker, MD, PhD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Katherine J. Aitchison, MD, PhD, Department of Psychiatry, University of Alberta, Alberta, Canada; Sven Bergmann, PhD, Department of Medical Genetics, University of Lausanne, Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland; Dorret I. Boomsma, PhD, Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands; Nick Craddock, MB, PhD, FMedSci, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Henry Wellcome Building, Cardiff, UK; Michael Gill, MD, Department of Psychiatry, Trinity Centre for Health Sciences, Dublin 8, Ireland; Florian Holsboer, MD, PhD, Max Planck Institute of Psychiatry, Munich, Germany; Jouke-Jan Hottenga, PhD, Department of Psychiatry, University of Alberta, Alberta, Canada; Ania Korszun, PhD, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Zoltan Kutalik, PhD, Department of Medical Genetics, University of Lausanne, Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland; Susanne Lucae, MD, PhD, Max Planck Institute of Psychiatry, Munich, Germany; Wolfgang Maier, MD, Department of Psychiatry, University of Bonn, Bonn, Germany; Ole Mors, MD, PhD, Research Department P, Aarhus University Hospital, Risskov, Denmark; Bertram Müller-Myhsok MD, Max Planck Institute of Psychiatry, Munich, Germany; Michael J. Owen, MB, PhD, FMedSci, MRC Centre for Neuropsychiatry Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK; Brenda W. J. H. Penninx, PhD, Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center/GGZ in Geest, Amsterdam, The Netherlands; Martin Preisig, MD, Department of Psychiatry, Lausanne University Hospital, 1008 Prilly-Lausanne, Switzerland; John Rice, PhD, Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA; Marcella Rietschel, MD, Central Institute of Mental Health, Mannheim, Germany; Federica Tozzi, MD, Genetics Division, Drug Discovery, GlaxoSmithKline Research and Development, Verona, Italy; Rudolf Uher, MD, PhD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK, and Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada; Peter Vollenweider, MD, PhD, Gerard Waeber, MD, PhD, Division of Internal Medicine, CHUV, Lausanne, Switzerland; Gonneke Willemsen, PhD, Department of Psychiatry, University of Alberta, Alberta, Canada; Ian W. Craig, PhD, Anne E. Farmer, MD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Cathryn M. Lewis, PhD, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, and Department of Medical and Molecular Genetics, School of Medicine, King's College London, UK; Gerome Breen, PhD, Peter McGuffin, MB, PhD, FMedSci, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK margarita.rivera_sanchez@kcl.ac.uk.
² Margarita Rivera, PhD, Department of Biochemistry and Molecular Biology II and Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain, and MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, Kinǵs College London, UK; Adam E. Locke, PhD, Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA; Tanguy Corre, PhD, Department of Medical Genetics, University of Lausanne, Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland; Darina Czamara, PhD, Christiane Wolf, PhD, Max Planck Institute of Psychiatry, Munich, Germany; Ana Ching-Lopez, Department of Psychiatry, School of Medicine, University of Granada, and Institute of Neurosciences Federico Olóriz, Centra de Investigación Biomédica, University of Granada, Spain; Yuri Milaneschi, PhD, Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center/GGZ in Geest, Amsterdam, The Netherlands; Stefan Kloiber, MD, Max Planck Institute of Psychiatry, Munich, Germany; Sara Cohen-Woods, PhD, School of Psychology, Flinders University, Adelaide, South Australia, Australia; James Rucker, MD, PhD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Katherine J. Aitchison, MD, PhD, Department of Psychiatry, University of Alberta, Alberta, Canada; Sven Bergmann, PhD, Department of Medical Genetics, University of Lausanne, Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland; Dorret I. Boomsma, PhD, Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands; Nick Craddock, MB, PhD, FMedSci, Department of Psychological Medicine and Neurology, Cardiff University School of Medicine, Henry Wellcome Building, Cardiff, UK; Michael Gill, MD, Department of Psychiatry, Trinity Centre for Health Sciences, Dublin 8, Ireland; Florian Holsboer, MD, PhD, Max Planck Institute of Psychiatry, Munich, Germany; Jouke-Jan Hottenga, PhD, Department of Psychiatry, University of Alberta, Alberta, Canada; Ania Korszun, PhD, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Zoltan Kutalik, PhD, Department of Medical Genetics, University of Lausanne, Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland; Susanne Lucae, MD, PhD, Max Planck Institute of Psychiatry, Munich, Germany; Wolfgang Maier, MD, Department of Psychiatry, University of Bonn, Bonn, Germany; Ole Mors, MD, PhD, Research Department P, Aarhus University Hospital, Risskov, Denmark; Bertram Müller-Myhsok MD, Max Planck Institute of Psychiatry, Munich, Germany; Michael J. Owen, MB, PhD, FMedSci, MRC Centre for Neuropsychiatry Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK; Brenda W. J. H. Penninx, PhD, Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center/GGZ in Geest, Amsterdam, The Netherlands; Martin Preisig, MD, Department of Psychiatry, Lausanne University Hospital, 1008 Prilly-Lausanne, Switzerland; John Rice, PhD, Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA; Marcella Rietschel, MD, Central Institute of Mental Health, Mannheim, Germany; Federica Tozzi, MD, Genetics Division, Drug Discovery, GlaxoSmithKline Research and Development, Verona, Italy; Rudolf Uher, MD, PhD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK, and Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada; Peter Vollenweider, MD, PhD, Gerard Waeber, MD, PhD, Division of Internal Medicine, CHUV, Lausanne, Switzerland; Gonneke Willemsen, PhD, Department of Psychiatry, University of Alberta, Alberta, Canada; Ian W. Craig, PhD, Anne E. Farmer, MD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Cathryn M. Lewis, PhD, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, and Department of Medical and Molecular Genetics, School of Medicine, King's College London, UK; Gerome Breen, PhD, Peter McGuffin, MB, PhD, FMedSci, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.

PMID: 28642257
PMCID: PMC5537566
DOI: 10.1192/bjp.bp.116.183475

Erratum in

Corrections.
[No authors listed] [No authors listed] Br J Psychiatry. 2017 Dec;211(6):401. doi: 10.1192/bjp.211.6.401. Br J Psychiatry. 2017. PMID: 29196407 Free PMC article. No abstract available.

Abstract

BackgroundDepression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.AimsTo confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.MethodThe sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.ResultsIn the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β = 0.12, P = 2.7 × 10^-4) and with the Han/Eskin random effects method (P = 1.4 × 10^-7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10^-8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTOConclusionsThis meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.

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Conflict of interest statement

Declaration of interestK.J.A., A.E.F. and P.M. have received consultancy fees and honoraria for participating in expert panels for pharmaceutical companies including GlaxoSmithKline (GSK). P.M. has received speaker's fees from Pfizer. K.J.A. has been on the advisory board for Bristol-Myers Squibb and Otsuka Pharmaceutical and in addition received consultancy fees including payment for lectures and educational presentations. She was previously a member of other advisory boards, receiving consultancy fees and honoraria, and has received research grants from various companies including Lundbeck and GSK. F.H. is co-founder of the biotech company Holsboer Maschmeyer Neuro Chemie GmbH (HMNC GmbH) in Germany. W.M. is a member of the advisory boards and has received fees for speaking from Lilly and Lundbeck. M.P. is part of advisory boards for Eli Lilly and Lundbeck.

Figures

**Fig. 1**
Forest plot showing interactions between *FTO*, depression and body mass index. GSK, GiaxoSmithKline study; MARS, Munich Antidepressant Response Signature project; NESDA/NTR, Netherlands Study of Depression and Anxiety/Netherlands Twin Register; RE, risk estimate.

See this image and copyright information in PMC

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Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals

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Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals

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