Single Nucleotide Polymorphism-Single Nucleotide Polymorphism Interactions Among Inflammation Genes in the Genetic Architecture of Blood Pressure in the Framingham Heart Study

被引:3
作者
Basson, Jacob J. [1 ]
de las Fuentes, Lisa [1 ,2 ]
Rao, Dabeeru C. [1 ]
机构
[1] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Med, Div Cardiovasc, St Louis, MO 63110 USA
关键词
blood pressure; false discovery rate; hypertension; inflammation; interaction; NF kappa B; single nucleotide polymorphism; GENOME-WIDE ASSOCIATION; 3 CANDIDATE GENES; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; ADIPOR2; GENE; HYPERTENSION; ADIPONECTIN; RESISTIN; VARIANTS;
D O I
10.1093/ajh/hpu132
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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.
引用
收藏
页码:248 / 255
页数:8
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