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

• Published in: British journal of psychiatry 2014-07, Vol.205 (1), p.24-28
• Main Authors: Hung, Chi-Fa, Rivera, Margarita, Craddock, Nick, Owen, Michael J., Gill, Michael, Korszun, Ania, Maier, Wolfgang, Mors, Ole, Preisig, Martin, Rice, John P., Rietschel, Marcella, Jones, Lisa, Middleton, Lefkos, Aitchison, Kathy J., Davis, Oliver S. P., Breen, Gerome, Lewis, Cathryn, Farmer, Anne, McGuffin, Peter
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Analysis; Biological and medical sciences; Bipolar disorder; Body Mass Index; Case-Control Studies; Causality; Depression; Depressive Disorder - etiology; Depressive Disorder - genetics; Female; Gene polymorphism; Genetic susceptibility; Genotype; Genotypes; Humans; Male; Medical sciences; Mendelian Randomization Analysis; Mental depression; Mental disorders; Metabolic diseases; Middle Aged; Miscellaneous; Mood disorders; Obesity; Obesity - complications; Obesity - genetics; Polymorphism, Single Nucleotide; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Regression analysis; Single-nucleotide polymorphism; Systematic review
• ISSN: 0007-1250; 1472-1465
• DOI: 10.1192/bjp.bp.113.130419

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. To investigate whether higher BMI increases the risk of major depression. 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. 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). 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.