A Mendelian randomization study to assess the causality of fasting glucose level for hypertension in African Americans

Authors

• SM Tajuddin
• MA Nalls
• AB Zonderman
• MK Evans

Abstract

Hypertension (HTN) causes significant morbidity and mortality, and disproportionately affects African Americans (AAs). Elevated fasting plasma glucose (FPG) is one of the risk factors of HTN identified through epidemiologic studies. Whether the association between FPG and HTN is causal is unknown. Using a Mendelian randomization (MR) analysis among 942 AAs in the Healthy Aging in Neighborhoods of Diversity across the Life Span study (HANDLS), we tested the hypothesis that elevated FPG is causally associated with HTN risk. To construct a FPG genetic score (GS) as an instrumental variable, we selected five significantly associated SNPs at TMEM163-MGAT5, LOC285692, and 9q32 loci. For epidemiological analysis, we fitted a multivariable adjusted logistic regression model to assess the association between FPG and risk of HTN. For MR analysis, we used a two-stage regression analysis (1) to assess the association between GS and FPG, and (2) to assess the association between genetically predicted FPG values and HTN risk. The GS was positively associated with FPG (beta=0.143, standard error=0.023, P=1.45E-9, F-statistic=37.3) but not with HTN risk (OR=0.90, 95%CI 0.56-1.46), which together suggest the GS is a strong instrumental variable. In epidemiological analysis, increased FPG was significantly associated with increased risk of HTN [OR = 2.03, 95% confidence interval (CI) 1.13-3.65, P=0.02]. In MR analysis, genetically elevated FPG was significantly associated with increased risk of HTN (causal OR = 15.08, 95%CI 12.98-17.19, P=0.01). Our findings provide the first evidence that the genetic loci that elevate FPG are causally associated with increased HTN risk among AA adults.

Scientific Focus Area: Genetics and Genomics

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