Interaction of gender and body mass index (BMI) reveals evidence of linkage for hypertension in the Framingham Heart Study

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Abstract
Background: Genetic heterogeneity and complex biologic mechanisms of blood pressure regulation pose significant challenges to the identification of susceptibility loci influencing hypertension. Previous linkage studies have reported regions of interest, but lack consistency across studies. Incorporation of covariates, in particular the interaction between two independent risk factors (gender and BMI) greatly improved our ability to detect linkage. Results: We report a highly significant signal for linkage to chromosome 2p, a region that has been implicated in previous linkage studies, along with several suggestive linkage regions. Conclusion: We demonstrate the importance of including covariates in the linkage analysis when the phenotype is complex.