Relationship between obesity and the risk of clinically significant depression: Mendelian randomisation study

Hung, C.-F., Rivera, M., Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Gill, M., Korszun, A., Maier, W., Mors, O., Preisig, M., Rice, J. P., Rietschel, M., Jones, L., Middleton, L., Aitchison, K. J., Davis, O. S. P., Breen, G., Lewis, C., 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. 10.1192/bjp.bp.113.130419

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Neuroscience and Mental Health Research Institute (NMHRI) Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Royal College of Psychiatrists
ISSN:	0007-1250
Last Modified:	28 Oct 2022 09:33
URI:	https://orca.cardiff.ac.uk/id/eprint/74906

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