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Relationship Between Obesity and the Risk of Clinically Significant Depression: Mendelian Randomisation Study

Hung, C-F. and Rivera, M. and Craddock, N. and Owen, M.J. and Gill, M. and Korszun, A. and Maier, W. and Mors, O. and Preisig, M. and Rice, J.P. and Reitschel, M. and Jones, Lisa and Middleton, L. and Aitchison, K.J. and Davis, O.S.P. and Breen, G. and Lewis, C. and Farmer, A. and McGuffin, P. (2014) Relationship Between Obesity and the Risk of Clinically Significant Depression: Mendelian Randomisation Study. British Journal of Psychiatry, 205 (1). pp. 24-28. ISSN Print: 0007-1250 Online:1472-1465

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Abstract

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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Uncontrolled Keywords: depression, obesity, mendelian randomisation, body mass index, causal relationship between obesity and major depression, linear
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Academic Departments > Institute of Health and Society
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Depositing User: Lisa Jones
Date Deposited: 16 Jan 2017 12:00
Last Modified: 16 Jan 2017 12:00
URI: https://eprints.worc.ac.uk/id/eprint/5235

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