Mendelian randomization analyses identify bidirectional causal relationships of obesity with psychiatric disorders

Abstract

Background: Obesity have been showed to be strongly associated with psychiatric disorders, but the exact causality and the direction of the relationship remain inconclusive. Thus, we aimed to identify the causal associations between obesity and psychiatric disorders using two-sample Mendelian randomization (MR).

Methods: Single-nucleotide polymorphisms associated with obesity, including body mass index (BMI), waist-hip ratio (WHR), and waist-hip ratio adjusted for BMI (WHRadjBMI), were extracted from a genome-wide association study of 694,649 European ancestry from the GIANT consortium. Summary level data for 10 psychiatric disorders were obtained from the Psychiatric Genomics Consortium. Inverse-variance weighted (IVW) method was used as the primary analysis, while several sensitivity analyses were applied to evaluate heterogeneity and pleiotropy.

Results: The main MR results suggested higher BMI or WHR was positively causally associated with an increased risk of attention deficit hyperactivity disorder (ADHD), anorexia nervosa (AN), post-traumatic stress disorder (PTSD), major depressive disorder (MDD) and Alzheimer's disease (ALZ), but negatively causally associated with an increased risk of obsessive-compulsive disorder (OCD) and schizophrenia. For the reverse direction, ADHD and MDD were associated with an increased risk of obesity, but schizophrenia and ALZ were associated with a decreased risk of obesity.

Conclusion: Our findings support evidence of causal relationships between obesity and ADHD, MDD, PTSD, ALZ, SCZ, AN, and OCD, and confirmed the bidirectional causal relationships between obesity and ADHD, MDD, SCZ, and ALZ.

Keywords: Causality; Mendelian randomization; Obesity; Psychiatric disorders.