Causal Effects of Positive Affect, Life Satisfaction, Depressive Symptoms, and Neuroticism on Kidney Function: A Mendelian Randomization Study

Significance Statement Poor psychologic wellbeing is prevalent in people with kidney function impairment. A Mendelian randomization investigation identified “causal” effects from psychologic wellbeing on kidney function. The analysis demonstrated that genetic predisposition for certain positive wellbeing senses causally decreases the risk of kidney function impairment. In contrast, genetically predicted negative wellbeing senses were causally linked to a higher risk of CKD, or a lower eGFR. Therefore, this study suggests health care providers in the nephrology field should be aware of the causal linkage between psychologic wellbeing and kidney function. Background Further investigation of the causal effects of psychologic wellbeing on kidney function is warranted. Methods In this Mendelian randomization (MR) study, genetic instruments for positive affect, life satisfaction, depressive symptoms, and neuroticism were introduced from a previous genome-wide association study meta-analysis of European individuals. Summary-level MR was performed using the CKDGen data of European ancestry ( n =567,460), and additional allele score–based MR was performed in the individual-level data of White British UK Biobank participants ( n =321,024). Results In summary-level MR with the CKDGen data, depressive symptoms were a significant causative factor for kidney function impairment (CKD OR, 1.45; 95% confidence interval, 1.07 to 1.96; eGFR change [%] beta −2.18; 95% confidence interval, −3.61 to −0.72) and pleiotropy-robust sensitivity analysis results supported the causal estimates. A genetic predisposition for positive affect was significantly associated with better kidney function (CKD OR, 0.69; 95% confidence interval, 0.52 to 0.91), eGFR change [%] beta 1.50; 95% confidence interval, 0.09 to 2.93) and sensitivity MR analysis results supported the finding for CKD outcome, but was nonsignificant for eGFR. Life satisfaction and neuroticism exposures showed nonsignificant causal estimates. In the UK Biobank with covariate-adjusted allele score MR analysis, allele scores for positive affect and life satisfaction were causally associated with reduced risk of CKD and higher eGFR. In contrast, neuroticism allele score was associated with increased risk of CKD and lower eGFR, and depressive symptoms allele score was associated with lower eGFR, but showed nonsignificant association with CKD. Conclusions Health care providers in the nephrology field should be aware of the causal linkage between psychologic wellbeing and kidney function.