title: Gene-smoking interactions identify several novel blood pressure loci in the Framingham Heart Study.
abstract: BACKGROUND
  Cardiovascular diseases are among the most significant health problems in the United States. Blood pressure (BP) variability has a genetic component, and most of the genetic variance remains to be identified. One promising strategy for gene discovery is genome-wide analysis of interactions between single nucleotide polymorphisms (SNPs) and environmental factors related to cardiovascular diseases.
  
  
  METHODS
  We investigated SNP-smoking interaction effects on BP in genome-wide data in 6,889 participants from the Framingham Heart Study. We performed the standard 1 degree of freedom (df) test of the interaction effect and the joint 2 df test of main and interaction effects. Three smoking measures were used: cigarettes per day (CPD), pack years of smoking, and smoking status.
  
  
  RESULTS
  We identified 7 significant and 21 suggestive BP loci. Identified through the joint 2 df test, significant SBP loci include: rs12149862 (P = 3.65×10(-9)) in CYB5B, rs2268365 (P = 4.85×10(-8)) in LRP2, rs133980 (P = 1.71×10(-8) with CPD and P = 1.07×10(-8) with pack-years) near MN1, and rs12634933 (P = 4.05×10(-8)) in MECOM. Through 1 df interaction analysis, 1 suggestive SBP locus at SNP rs8010717 near NRXN3 was identified using all 3 smoking measures (P = 3.27×10(-7) with CPD, P = 1.03×10(-7) with pack-years, and P = 1.19×10(-7) with smoking status).
  
  
  CONCLUSIONS
  Several of these BP loci are biologically plausible, providing physiological connection to BP regulation. Our study demonstrates that SNP-smoking interactions can enhance gene discovery and provide insight into novel pathways and mechanisms regulating BP.
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri; yunju@wubios.wustl.edu.
authors.forename: Yun J
authors.initials: YJ
authors.lastname: Sung
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri; Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Lisa
authors.initials: L
authors.lastname: de las Fuentes
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Karen L
authors.initials: KL
authors.lastname: Schwander
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Jeannette
authors.initials: J
authors.lastname: Simino
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri; Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Dabeeru C
authors.initials: DC
authors.lastname: Rao
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012907:Smoking / Q000503:physiopathology*
keywords: blood pressure; gene–environment interaction; genome-wide association study; hypertension; single nucleotide polymorphisms; smoking.