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

Margarita Rivera; Adam E. Locke; Tanguy Corre; Darina Czamara; Christiane Wolf; Ana Ching-Lopez; Yuri Milaneschi; Stefan Kloiber; Sara Cohen-Woods; James Rucker; Katherine J. Aitchison; Sven Bergmann; Dorret I. Boomsma; Nick Craddock; Michael Gill; Florian Holsboer; Jouke Jan Hottenga; Ania Korszun; Zoltan Kutalik; Susanne Lucae; Wolfgang Maier; Ole Mors; Bertram Muller-Myhsok; Michael J. Owen; Brenda W.J.H. Penninx; Martin Preisig; John Rice; Marcella Rietschel; Federica Tozzi; Rudolf Uher; Peter Vollenweider; Gerard Waeber; Gonneke Willemsen; Ian W. Craig; Anne E. Farmer; Cathryn M. Lewis; Gerome Breen; Peter McGuffin

doi:10.1192/bjp.bp.116.183475

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

Margarita Rivera, Adam E. Locke, Tanguy Corre, Darina Czamara, Christiane Wolf, Ana Ching-Lopez, Yuri Milaneschi, Stefan Kloiber, Sara Cohen-Woods, James Rucker, Katherine J. Aitchison, Sven Bergmann, Dorret I. Boomsma, Nick Craddock, Michael Gill, Florian Holsboer, Jouke Jan Hottenga, Ania Korszun, Zoltan Kutalik, Susanne LucaeWolfgang Maier, Ole Mors, Bertram Muller-Myhsok, Michael J. Owen, Brenda W.J.H. Penninx, Martin Preisig, John Rice, Marcella Rietschel, Federica Tozzi, Rudolf Uher, Peter Vollenweider, Gerard Waeber, Gonneke Willemsen, Ian W. Craig, Anne E. Farmer, Cathryn M. Lewis, Gerome Breen, Peter McGuffin

Medicine

Research output: Contribution to journal › Review article › peer-review

51 Citations (Scopus)

Abstract

Background Depression 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. Aims To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis. Method The 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. Results In 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 metaanalysis 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 FTO. Conclusions This 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.

Original language	English
Pages (from-to)	70-76
Number of pages	7
Journal	British Journal of Psychiatry
Volume	211
Issue number	2
DOIs	https://doi.org/10.1192/bjp.bp.116.183475
Publication status	Published - Aug 2017

Bibliographical note

Funding Information:
This study was funded by the Medical Research Council, UK, and GlaxoSmithKline (G0701420). The GENDEP study was funded by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. M.R. was supported by a fellowship from the Marie Curie Research Grants Scheme (FP7-626235). J.R. was supported by a fellowship from the Wellcome Trust (086635). K.J.A. holds an Alberta Centennial Addiction and Mental Health Research Chair funded by the Government of Alberta. This work was funded in part by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London. This article presents independent research in part funded by the NIHR. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The CoLaus/PsyCoLaus was funded by four grants from the Swiss National Science Foundation (#32003B-105993, #32003B-118308, #33CSC0-122661 and #139468), the Faculty of Biology and Medicine of Lausanne and two grants from GlaxoSmithKline Clinical Genetics. The MARS project was funded by the Max Planck Society and in part by a research grant from the German Federal Ministry for Education and Research (BMBF) in the framework of the National Genome Research Network (NGFN2 and NGFN-Plus, FKZ 01GS0481) and by the BMBF Programme 'Molecular Diagnostics: Validation of Biomarkers for Diagnosis and Outcome in Major Depression' (01ES0811). Netherland Twin Register and Netherlands Study of Depression and Anxiety (NESDA): funding was obtained from the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants Middelgroot-911-09-032, Spinozapremie 56-464-14192, Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMW 10-000-1002), Center for Medical Systems Biology (CSMB, NWO Genomics), Genetic influences on stability and change in psychopathology from childhood to young adulthood (ZonMW 912-10-020), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRl-NL, 184.021.00A VU University's Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); and the European Science Council (ERC Advanced, 230374). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health, Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera institute, Sioux Falls, South Dakota, USA and the National Institutes of Health (NIH R01 HD042157-01A1, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995).

Publisher Copyright:
© The Royal College of Psychiatrists 2017.

ASJC Scopus Subject Areas

Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1192/bjp.bp.116.183475

Cite this

Rivera, M., Locke, A. E., Corre, T., Czamara, D., Wolf, C., Ching-Lopez, A., Milaneschi, Y., Kloiber, S., Cohen-Woods, S., Rucker, J., Aitchison, K. J., Bergmann, S., Boomsma, D. I., Craddock, N., Gill, M., Holsboer, F., Hottenga, J. J., Korszun, A., Kutalik, Z., ... McGuffin, P. (2017). Interaction between the FTO gene, body mass index and depression: Meta-analysis of 13701 individuals. British Journal of Psychiatry, 211(2), 70-76. https://doi.org/10.1192/bjp.bp.116.183475

Rivera, M, Locke, AE, Corre, T, Czamara, D, Wolf, C, Ching-Lopez, A, Milaneschi, Y, Kloiber, S, Cohen-Woods, S, Rucker, J, Aitchison, KJ, Bergmann, S, Boomsma, DI, Craddock, N, Gill, M, Holsboer, F, Hottenga, JJ, Korszun, A, Kutalik, Z, Lucae, S, Maier, W, Mors, O, Muller-Myhsok, B, Owen, MJ, Penninx, BWJH, Preisig, M, Rice, J, Rietschel, M, Tozzi, F, Uher, R, Vollenweider, P, Waeber, G, Willemsen, G, Craig, IW, Farmer, AE, Lewis, CM, Breen, G & McGuffin, P 2017, 'Interaction between the FTO gene, body mass index and depression: Meta-analysis of 13701 individuals', British Journal of Psychiatry, vol. 211, no. 2, pp. 70-76. https://doi.org/10.1192/bjp.bp.116.183475

@article{d5ba3f54147d432f8cd7a88431872958,

title = "Interaction between the FTO gene, body mass index and depression: Meta-analysis of 13701 individuals",

abstract = "Background Depression 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. Aims To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis. Method The 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. Results In 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 metaanalysis 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 FTO. Conclusions This 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.",

author = "Margarita Rivera and Locke, {Adam E.} and Tanguy Corre and Darina Czamara and Christiane Wolf and Ana Ching-Lopez and Yuri Milaneschi and Stefan Kloiber and Sara Cohen-Woods and James Rucker and Aitchison, {Katherine J.} and Sven Bergmann and Boomsma, {Dorret I.} and Nick Craddock and Michael Gill and Florian Holsboer and Hottenga, {Jouke Jan} and Ania Korszun and Zoltan Kutalik and Susanne Lucae and Wolfgang Maier and Ole Mors and Bertram Muller-Myhsok and Owen, {Michael J.} and Penninx, {Brenda W.J.H.} and Martin Preisig and John Rice and Marcella Rietschel and Federica Tozzi and Rudolf Uher and Peter Vollenweider and Gerard Waeber and Gonneke Willemsen and Craig, {Ian W.} and Farmer, {Anne E.} and Lewis, {Cathryn M.} and Gerome Breen and Peter McGuffin",

note = "Funding Information: This study was funded by the Medical Research Council, UK, and GlaxoSmithKline (G0701420). The GENDEP study was funded by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. M.R. was supported by a fellowship from the Marie Curie Research Grants Scheme (FP7-626235). J.R. was supported by a fellowship from the Wellcome Trust (086635). K.J.A. holds an Alberta Centennial Addiction and Mental Health Research Chair funded by the Government of Alberta. This work was funded in part by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London. This article presents independent research in part funded by the NIHR. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The CoLaus/PsyCoLaus was funded by four grants from the Swiss National Science Foundation (#32003B-105993, #32003B-118308, #33CSC0-122661 and #139468), the Faculty of Biology and Medicine of Lausanne and two grants from GlaxoSmithKline Clinical Genetics. The MARS project was funded by the Max Planck Society and in part by a research grant from the German Federal Ministry for Education and Research (BMBF) in the framework of the National Genome Research Network (NGFN2 and NGFN-Plus, FKZ 01GS0481) and by the BMBF Programme 'Molecular Diagnostics: Validation of Biomarkers for Diagnosis and Outcome in Major Depression' (01ES0811). Netherland Twin Register and Netherlands Study of Depression and Anxiety (NESDA): funding was obtained from the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants Middelgroot-911-09-032, Spinozapremie 56-464-14192, Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMW 10-000-1002), Center for Medical Systems Biology (CSMB, NWO Genomics), Genetic influences on stability and change in psychopathology from childhood to young adulthood (ZonMW 912-10-020), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRl-NL, 184.021.00A VU University's Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); and the European Science Council (ERC Advanced, 230374). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health, Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera institute, Sioux Falls, South Dakota, USA and the National Institutes of Health (NIH R01 HD042157-01A1, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995). Publisher Copyright: {\textcopyright} The Royal College of Psychiatrists 2017.",

year = "2017",

month = aug,

doi = "10.1192/bjp.bp.116.183475",

language = "English",

volume = "211",

pages = "70--76",

journal = "British Journal of Psychiatry",

issn = "0007-1250",

publisher = "Royal College of Psychiatrists",

number = "2",

}

TY - JOUR

T1 - Interaction between the FTO gene, body mass index and depression

T2 - Meta-analysis of 13701 individuals

AU - Rivera, Margarita

AU - Locke, Adam E.

AU - Corre, Tanguy

AU - Czamara, Darina

AU - Wolf, Christiane

AU - Ching-Lopez, Ana

AU - Milaneschi, Yuri

AU - Kloiber, Stefan

AU - Cohen-Woods, Sara

AU - Rucker, James

AU - Aitchison, Katherine J.

AU - Bergmann, Sven

AU - Boomsma, Dorret I.

AU - Craddock, Nick

AU - Gill, Michael

AU - Holsboer, Florian

AU - Hottenga, Jouke Jan

AU - Korszun, Ania

AU - Kutalik, Zoltan

AU - Lucae, Susanne

AU - Maier, Wolfgang

AU - Mors, Ole

AU - Muller-Myhsok, Bertram

AU - Owen, Michael J.

AU - Penninx, Brenda W.J.H.

AU - Preisig, Martin

AU - Rice, John

AU - Rietschel, Marcella

AU - Tozzi, Federica

AU - Uher, Rudolf

AU - Vollenweider, Peter

AU - Waeber, Gerard

AU - Willemsen, Gonneke

AU - Craig, Ian W.

AU - Farmer, Anne E.

AU - Lewis, Cathryn M.

AU - Breen, Gerome

AU - McGuffin, Peter

N1 - Funding Information: This study was funded by the Medical Research Council, UK, and GlaxoSmithKline (G0701420). The GENDEP study was funded by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. M.R. was supported by a fellowship from the Marie Curie Research Grants Scheme (FP7-626235). J.R. was supported by a fellowship from the Wellcome Trust (086635). K.J.A. holds an Alberta Centennial Addiction and Mental Health Research Chair funded by the Government of Alberta. This work was funded in part by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London. This article presents independent research in part funded by the NIHR. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The CoLaus/PsyCoLaus was funded by four grants from the Swiss National Science Foundation (#32003B-105993, #32003B-118308, #33CSC0-122661 and #139468), the Faculty of Biology and Medicine of Lausanne and two grants from GlaxoSmithKline Clinical Genetics. The MARS project was funded by the Max Planck Society and in part by a research grant from the German Federal Ministry for Education and Research (BMBF) in the framework of the National Genome Research Network (NGFN2 and NGFN-Plus, FKZ 01GS0481) and by the BMBF Programme 'Molecular Diagnostics: Validation of Biomarkers for Diagnosis and Outcome in Major Depression' (01ES0811). Netherland Twin Register and Netherlands Study of Depression and Anxiety (NESDA): funding was obtained from the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants Middelgroot-911-09-032, Spinozapremie 56-464-14192, Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMW 10-000-1002), Center for Medical Systems Biology (CSMB, NWO Genomics), Genetic influences on stability and change in psychopathology from childhood to young adulthood (ZonMW 912-10-020), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRl-NL, 184.021.00A VU University's Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); and the European Science Council (ERC Advanced, 230374). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health, Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera institute, Sioux Falls, South Dakota, USA and the National Institutes of Health (NIH R01 HD042157-01A1, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995). Publisher Copyright: © The Royal College of Psychiatrists 2017.

PY - 2017/8

Y1 - 2017/8

N2 - Background Depression 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. Aims To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis. Method The 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. Results In 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 metaanalysis 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 FTO. Conclusions This 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.

AB - Background Depression 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. Aims To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis. Method The 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. Results In 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 metaanalysis 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 FTO. Conclusions This 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.

UR - http://www.scopus.com/inward/record.url?scp=85026820801&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026820801&partnerID=8YFLogxK

U2 - 10.1192/bjp.bp.116.183475

DO - 10.1192/bjp.bp.116.183475

M3 - Review article

C2 - 28642257

AN - SCOPUS:85026820801

SN - 0007-1250

VL - 211

SP - 70

EP - 76

JO - British Journal of Psychiatry

JF - British Journal of Psychiatry

IS - 2

ER -

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

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this