Relationship between obesity and the risk of clinically significant depression: Mendelian randomisation study
Chi-Fa Hung1, Margarita Rivera1, Nick Craddock1
1Chi-Fa Hung, MD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry at King's College London, UK, and Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Margarita Rivera, PhD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry at King's College London, UK, and CIBERSAM, University of Granada, Section of Psychiatry, Institute of Neurosciences, Biomedical Research Centre (CIBM), Granada, Spain; Nick Craddock, PhD, FRCPsych, FMedSci, Michael J. Owen, PhD, FRCPsych, FMedSci, Department of Psychological Medicine, School of Medicine, Cardiff University, UK; Michael Gill, PhD, Department of Psychiatry, Trinity Centre for Health Sciences, St James' Hospital, Dublin, Ireland; Ania Korszun, PhD, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary's University of London, UK; Wolfgang Maier, PhD, Psychiatrie und Psychotherapie, Universitätsklinikum Bonn, Bonn, Germany; Ole Mors, PhD, Research Department P, Aarhus University Hospital, Risskov, Aarhus, Denmark; Martin Preisig, MD, Department of Adult Psychiatry, University Hospital of Lausanne, Prilly-Lausanne, Switzerland; John P. Rice, PhD, Department of Psychiatry, Washington University, St Louis, Missouri, USA; Marcella Rietschel, MD, Central Institute of Mental Health, Mannheim, Germany; Lisa Jones, PhD, Department of Psychiatry, School of Clinical and Experimental Medicine, University of Birmingham, UK; Lefkos Middleton, MD,Division of Neuroscience and Mental Health, Imperial College London, UK; Kathy J. Aitchison, PhD, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry at King's College London, UK and Department of Psychiatry, University of Alberta, Alberta, Canada; Oliver S. P. Davis, PhD, University College London Genetics Institute, Department of Genetics, Evolution and Environment, University Colleg
Background:
Obesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue.
Aims:
To investigate whether higher BMI increases the risk of major depression.
Method:
Two instrumental variable analyses were conducted to test the causal relationship between obesity and major depression in RADIANT, a large case-control study of major depression. We used a single nucleotide polymorphism (SNP) in FTO and a genetic risk score (GRS) based on 32 SNPs with well-established associations with BMI.
Results:
Linear regression analysis, as expected, showed that individuals carrying more risk alleles of FTO or having higher score of GRS had a higher BMI. Probit regression suggested that higher BMI is associated with increased risk of major depression. However, our two instrumental variable analyses did not support a causal relationship between higher BMI and major depression (FTO genotype: coefficient -0.03, 95% CI -0.18 to 0.13, P = 0.73; GRS: coefficient -0.02, 95% CI -0.11 to 0.07, P = 0.62).
Conclusions:
Our instrumental variable analyses did not support a causal relationship between higher BMI and major depression. The positive associations of higher BMI with major depression in probit regression analyses might be explained by reverse causality and/or residual confounding.
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