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/m²), class 1 obesity (BMI ≥ 30 kg/m²), and class 2 obesity (BMI ≥ 35 kg/m²) 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 β = 0.033; 95 %CI 0.008–0.057; P = 0.010) and class 1 obesity(IVW β = −0.033; 95 %CI -0.047 – -0.020; P < 0.001) were causally associated with increased depressive symptoms. Genetically predicted class 2 obesity(IVW β = 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.