title: Single nucleotide polymorphism-single nucleotide polymorphism interactions among inflammation genes in the genetic architecture of blood pressure in the Framingham Heart Study.
abstract: BACKGROUND
  Hypertension is a major global health burden, but, although systolic and diastolic blood pressure (BP) each have estimated heritability of at least 30%, <3% of their variance has been attributed to particular genetic variants. Few studies have shown interactions between pairs of single nucleotide polymorphisms (SNPs) to be associated with BP. Although many studies use a Bonferroni correction for multiple testing to control type I error, thereby potentially reducing power, false discovery rate (FDR) approaches are also used in genome-wide studies. Renal ion balance genes have been associated with BP regulation, but, although inflammation has been studied in connection with BP, few studies have reported associations between inflammation genes and BP.
  
  
  METHODS
  We analyzed SNP-SNP interactions among 31 SNPs from genes involved in renal ion balance and 30 SNPs from genes involved in inflammation using data from the Framingham Heart Study.
  
  
  RESULTS
  No evidence of association was found for interactions among renal ion balance SNPs for either systolic or diastolic BP. A group of 3 interactions involving 6 inflammation genes (IKBKB-NFKBIA, IKBKE-CHUK, and ADIPOR2-RETN) showed evidence of association with diastolic BP with an FDR of 4.2%; no single interaction reached experiment-wide significance.
  
  
  CONCLUSIONS
  This study identified promising and biologically plausible candidates for interactions between inflammation genes that may be associated with DBP. Analysis using the FDR may allow detection of signals in the presence of modest noise (false positives) that a stringent approach based on Bonferroni-corrected P value thresholds may miss.
authors: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA; jjbasson@wustl.edu.
authors: Jacob J
authors: JJ
authors: Basson
authors: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA; Department of Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.
authors: Lisa
authors: L
authors: de las Fuentes
authors: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA;
authors: Dabeeru C
authors: DC
authors: Rao
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000235:genetics*; D015331:Cohort Studies; D004843:Epistasis, Genetic; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D051550:I-kappa B Kinase / Q000235:genetics; D020672:I-kappa B Proteins / Q000235:genetics; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin / Q000235:genetics; D052243:Resistin / Q000235:genetics
chemical_list: C475420:ADIPOR2 protein, human; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; C499624:RETN protein, human; D054419:Receptors, Adiponectin; D052243:Resistin; D000072000:NF-KappaB Inhibitor alpha; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human
keywords: NFκB; blood pressure; false discovery rate; hypertension; inflammation; interaction; single nucleotide polymorphism.