Gene-Education Interactions Identify Novel Blood Pressure Loci in the Framingham Heart Study

BACKGROUND: Blood pressure (BP) variability has a genetic component, most of which has yet to be attributed to specific variants. One promising strategy for gene discovery is analysis of interactions between single-nucleotide polymorphisms (SNPs) and BP-related factors, including age, sex, and body mass index (BMI). Educational attainment, a marker for socioeconomic status, has effects on both BP and BMI. METHODS: We investigated SNP-education interaction effects on BP in genome-wide data on 3,836 subjects in families from the Framingham Heart Study. The ABEL suite was used to adjust for age, sex, BMI, medication use, and kinship and to perform 1 degree-of-freedrom (df) and 2 df SNP-education interaction tests. RESULTS: An SNP in PTN was associated with increased systolic BP (5.4mm Hg per minor allele) in those without a bachelor's degree but decreased systolic BP (1.6mm Hg per allele) in those with a bachelor's degree (2 df; P = 2.08 × 10(-8)). An SNP in TOX2 was associated with increased diastolic BP (DBP; 4.1mm Hg per minor allele) in those with no more educational attainment than high school but decreased DBP in those with education past high school (-0.7; 1 df; P = 3.74 × 10(-8)). Three suggestive associations were also found: in MYO16 (pulse pressure: 2 df; P = 2.89 × 10(-7)), in HAS2 (DBP: 1 df; P = 1.41 × 10(-7)), and in DLEU2 (DBP: 2 df; P = 1.93 × 10(-7)). All 5 genes are related to BP, including roles in vasodilation and angiogenesis for PTN and TOX2. CONCLUSIONS: PTN and TOX2 are associated with BP. Analyzing SNP-education interactions may detect novel associations. Education may be a surrogate for unmeasured exposures and behaviors modifying SNP effects on BP.