Abstract P127: Gene-Lifestyle Interactions Detect Novel Blood Pressure Loci

Abstract

Introduction: Gene-lifestyle interaction effects (GxE more generally) on blood pressure (BP), a promising approach for novel loci discovery, is being actively pursued in the CHARGE Gene-Lifestyle Interactions Working Group using individual lifestyle domains, such as smoking status. Objectives: To explore the potential utility of a “lifestyle index” (aggregating multiple lifestyle domains) for identifying novel BP loci in a GxE context, we performed genome-wide interaction analysis with two lifestyle index variables. Methods: For each of 6,257 subjects (19 – 80 years, 46.9% male) in the Framingham Heart Study SHARe dataset, lifestyle index was defined as the sum of risk scores for four lifestyle factors: smoking status (0 = Never, 1 = Former, 2 = Current), alcohol intake (0 = Moderate, 1 = Never, 2 = Heavy), physical activity (0 = Active, 1= Inactive), and educational level (0=College degree, 1 = Some college, and 2 = No college). We examined GxE for systolic BP using the quantitative index (ranging from 0 to 7) and a binary form of the index (≥ vs < the median), while adjusting for sex, age, and kinship. Promising loci were identified using a 2 df joint test of main and interaction effects at α = 5 x 10 -6 . Results: Sixteen promising single nucleotide polymorphisms (SNPs) representing 8 loci were found when using the quantitative lifestyle index, and 43 SNPs representing 4 loci when using the binary lifestyle index (Table 1), with only one locus common to both indices. Of the 11 unique loci detected, 3 are within 500 kb of known BP loci and 6 are in or near a gene with a known function. Conclusions: We demonstrate that a composite of multiple lifestyle factors can enhance novel discovery.