The association between overweight and varying degrees of obesity with subjective well-being and depressive symptoms: A two sample Mendelian randomization study

Objective: This study utilized the Mendelian randomization (MR) method to elucidate the causal relationship between genetically predicted overweight and various degrees of obesity with depressive symptoms and subjective well-being (SWB). Methods: Pooled genome-wide association studies (GWAS) data for overweight (BMI >= 25 kg/m(2)), class 1 obesity (BMI >= 30 kg/m(2)), and class 2 obesity (BMI >= 35 kg/m(2)) were used as exposures. Summary GWAS data for depressive symptoms and SWB were used as outcomes. Multiple MR methods, primarily inverse-variance weighted (IVW), were applied, and sensitivity analyses were conducted to assess heterogeneity and pleiotropy. Results: The MR analysis provided evidence that genetically predicted overweight(IVW beta = 0.033; 95 %CI 0.008-0.057; P = 0.010) and class 1 obesity(IVW beta = -0.033; 95 %CI -0.047 - -0.020; P < 0.001) were causally associated with increased depressive symptoms. Genetically predicted class 2 obesity(IVW beta = 1.428; 95 %CI 1.193-1.710; P < 0.001) were associated with reduced SWB. There was no strong evidence of a causal association between genetically predicted overweight and class 1 obesity with SWB. Similarly, genetically predicted class 2 and class 3 obesity did not show strong evidence of a causal association with depressive symptoms. Sensitivity analysis revealed relationships of a similar magnitude. Conclusion: This genetically informed MR study suggests that Overweight and class 1 obesity may causally increased depressive symptoms but not decrease SWB. In contrast, class 2 obesity may causally decrease SWB but not increase depressive symptoms.