Investigating causal effects of income on health using two-sample Mendelian randomisation.

Background: Income is associated with many health outcomes, but it is unclear how far this reflects a causal relationship. Mendelian randomisation (MR) uses genetic variation between individuals to investigate causal effects and may overcome some of the confounding issues inherent in many observational study designs.

Methods: We used two-sample MR using data from unrelated individuals to estimate the effect of log occupational income on indicators of mental health, physical health, and health-related behaviours. We investigated pleiotropy (direct effects of genotype on the outcome) using robust MR estimators, CAUSE, and multivariable MR including education as a co-exposure. We also investigated demographic factors and dynastic effects using within-family analyses, and misspecification of the primary phenotype using bidirectional MR and Steiger filtering.

Results: We found that a 10% increase in income lowered the odds of depression (OR 0.92 [95% CI 0.86-0.98]), death (0.91 [0.86-0.96]), and ever-smoking (OR 0.91 [0.86-0.96]), and reduced BMI (- 0.06 SD [- 0.11, - 0.003]). We found little evidence of an effect on alcohol consumption (- 0.02 SD [- 0.01, 0.05]) or subjective wellbeing (0.02 SD [- 0.003, 0.04]), or on two negative control outcomes, childhood asthma (OR 0.99 [0.87, 1.13]) and birth weight (- 0.02 SD, [- 0.01, 0.05]). Within-family analysis and multivariable MR including education and income were imprecise, and there was substantial overlap between the genotypes associated with income and education: out of 36 genetic variants significantly associated with income, 29 were also significantly associated with education.

Conclusions: MR evidence provides some limited support for causal effects of income on some mental health outcomes and health behaviours, but the lack of reliable evidence from approaches accounting for family-level confounding and potential pleiotropic effects of education places considerable caveats on this conclusion. MR may nevertheless be a useful complement to other observational study designs since its assumptions and limitations are radically different. Further research is needed using larger family-based genetic cohorts, and investigating the overlap between income and other socioeconomic measures.