Gene-education interactions identify novel blood pressure loci in the framingham heart study

Jacob Basson, Yun Ju Sung, Karen Schwander, Rezart Kume, Jeannette Simino, Lisa De Las Fuentes, Dabeeru Rao

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

BACKGROUNDBlood 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.METHODSWe 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.RESULTSAn 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.CONCLUSIONSPTN 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.

Original languageEnglish
Pages (from-to)431-444
Number of pages14
JournalAmerican Journal of Hypertension
Volume27
Issue number3
DOIs
StatePublished - Mar 2014

Keywords

  • GWAS
  • blood pressure
  • educational attainment
  • gene-education interaction
  • hypertension
  • interaction

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