Mendelian Randomization of Arsenic Metabolism as a Risk Factor for Hypertensive- and Diabetes-Related Traits among Adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Cohort

Abstract

Much of the research that connects hypertension and diabetes to arsenic has been conducted in populations exposed through drinking water. Recently, dietary rice has been recognized as a significant source of arsenic. The objective of this analysis was to evaluate whether arsenic metabolism efficiency is associated with hypertension and diabetes using a Mendelian randomization framework in a population with high rice consumption but no known water arsenic exposure.Using 12,689 participants from the Hispanic Community Health Study/Study of Latinos, this study examined the relationship between estimated arsenic metabolism efficiency (defined as the percentages of inorganic arsenic, monomethylarsenate (MMA), and dimethylarsinate (DMA) species) and three hypertensive traits and seven diabetes-related traits. The analyses implemented a two-stage Mendelian randomization approach, with the genotype-arsenic metabolism relationships extracted from published literature, and the genotype-trait relationships estimated from a mixed-effect linear model within the HCHS/SOL population that controlled for the complex survey design and admixed ancestry. The analysis was stratified by rice consumption, dichotomized at the top 10th percentile.Among high consumers of rice, each estimated percentage point increase in MMA was associated with increases of 1.08 mmHg in systolic blood pressure and 0.82 mmHg in diastolic (p=0.047 and 0.0167, respectively). Inorganic arsenic was similarly associated with increased diastolic blood pressure (1.1 mmHg/percentage point; p=0.021). DMA, which represents more efficient arsenic metabolism, was associated with lowered diastolic blood pressure (-0.5 mmHg/percentage point; p=0.017). Among low rice consumers, no associations were observed. Evidence for a relationship with diabetes was equivocal.This suggests that dietary arsenic exposure through rice may be a contributor to high blood pressure in the Hispanic/Latino community.