The Effect of BMI and Type 2 Diabetes on Socioeconomic Status: A Two-Sample Multivariable Mendelian Randomization Study

RESULTS

In total, we included 69 SNPs for BMI and 42 SNPs for T2D, which overlapped at two distinct loci: FTO and TCF7L2 (Supplementary Table 2). Results of the univariable MR analysis indicated that a higher BMI was associated with a lower household income (β=20.092; 95% CI 20.138; 20.047) and with a higher regional deprivation (β=0.051; 95% CI 0.022; 0.079) (Table 1).

Diabetes did not have any effect on the socioeconomic outcomes considered. All analyses, except for BMI on income, presented low to middle levels of heterogeneity (异质性，不均一性) (I 2 5 0–57%), indicating good validity of the instruments. The difference between MR Egger and IVW estimates and a significant MR Egger intercept indicated the presence of horizontal pleiotropy, highlighting the need for multivariable MR analysis. The resulting effects from the multivariable MR analysis (Table 1) revealed that the direct effect of BMI controlling for diabetes was lower than in the univariable setting but still significant for both household income (b 5 20.089; 95% CI 20.13; 20.048) and regional deprivation (b 5 0.049; 95% CI 0.023; 0.075). Again, no effect of diabetes on socioeconomic outcomes could be observed. The results from the MR Egger regression were almost identical to the estimates resulting from the IVW regression, indicating that the multivariable approach successfully accounted for the bias resulting from horizontal pleiotropy in the univariable setting. All results were robust to the use of alternative estimation methods (Supplementary Material 3) and to the exclusion of other potentially pleiotropic SNPs (Supplementary Material 4).

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