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International Journal of Genomics
Volume 2017, Article ID 7208318, 9 pages
Research Article

An Exploration of Gene-Gene Interactions and Their Effects on Hypertension

1School of Nursing, University of Rochester, Rochester, NY, USA
2Department of Internal Medicine, Cardiology Division, University of Rochester Medical Center, Rochester, NY, USA
3Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA

Correspondence should be addressed to Ying Meng; ude.retsehcor.cmru@gnem_gniy

Received 6 February 2017; Accepted 24 April 2017; Published 31 May 2017

Academic Editor: Margarita Hadzopoulou-Cladaras

Copyright © 2017 Ying Meng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Hypertension tends to perpetuate in families and the heritability of hypertension is estimated to be around 20–60%. So far, the main proportion of this heritability has not been found by single-locus genome-wide association studies. Therefore, the current study explored gene-gene interactions that have the potential to partially fill in the missing heritability. A two-stage discovery-confirmatory analysis was carried out in the Framingham Heart Study cohorts. The first stage was an exhaustive pairwise search performed in 2320 early-onset hypertensive cases with matched normotensive controls from the offspring cohort. Then, identified gene-gene interactions were assessed in an independent set of 694 subjects from the original cohort. Four unique gene-gene interactions were found to be related to hypertension. Three detected genes were recognized by previous studies, and the other 5 loci/genes (MAN1A1, LMO3, NPAP1/SNRPN, DNAL4, and RNA5SP455/KRT8P5) were novel findings, which had no strong main effect on hypertension and could not be easily identified by single-locus genome-wide studies. Also, by including the identified gene-gene interactions, more variance was explained in hypertension. Overall, our study provides evidence that the genome-wide gene-gene interaction analysis has the possibility to identify new susceptibility genes, which can provide more insights into the genetic background of blood pressure regulation.