Mendelian randomization analysis identified causal Association of Childhood Obesity with adult major depressive disorder

Abstract

Childhood obesity is associated with adult major depressive disorder (MDD), but their causality is not clear. We performed a two-sample Mendelian randomization (MR) analysis to explore the causality of childhood body mass index (BMI) and childhood obesity on MDD, followed by a multivariable MR (MVMR) analysis to investigate the potential role of adult BMI in mediating such effect. We accessed genome-wide association summary statistics of childhood BMI, childhood obesity, adult BMI and adult MDD from the Early Growth Genetics consortium (nBMI =47 541, nobesity =24 160), the Genetic Investigation of Anthropometric Traits consortium (nadult_BMI =∼700 000) and the Psychiatric Genomics consortium (nMDD =500 199), respectively. The MR-PRESSO test was performed to remove SNPs with potential pleiotropic effect. The MR analysis was performed by inverse-variance weighted test. Further sensitivity analyses, including the MR-Egger intercept test and leave-one-out analysis, were performed to evaluate the reliability of the results. Our study found that childhood obesity might increase the odds of developing MDD in adults (OR=1.03, 95% CI: 1.01-1.06, p=2.6 × 10-3 ). Children with higher BMI were more likely to develop MDD in adulthood, with an OR of 1.12 per standard deviation score (SDS) increase in BMI (95% CI: 1.07-1.17, p=4.4 × 10-7 ). Sensitivity analyses verified the reliability of the causality between childhood BMI/obesity and MDD. Further MVMR results revealed that the impact of childhood BMI on MDD risk was predominantly mediated by adult BMI. Our findings provided evidence of a causal relationship between childhood BMI/obesity and adult MDD, thus providing new insights into the prevention of MDD.