Next Article in Journal
D181A Site-Mutagenesis Enhances Both the Hydrolyzing and Transfructosylating Activities of BmSUC1, a Novel β-Fructofuranosidase in the Silkworm Bombyx mori
Next Article in Special Issue
Liddle Syndrome: Review of the Literature and Description of a New Case
Previous Article in Journal
The Role of Long Non-Coding RNAs in Hepatocarcinogenesis
Previous Article in Special Issue
The Low-Renin Hypertension Phenotype: Genetics and the Role of the Mineralocorticoid Receptor
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2018, 19(3), 688; https://doi.org/10.3390/ijms19030688

Advances in the Genetics of Hypertension: The Effect of Rare Variants

1
Department of Medical Sciences, University of Turin, 10126 Turin, Italy
2
Italian Institute for Genomic Medicine (IIGM, Formerly HuGeF), 10126 Turin, Italy
*
Author to whom correspondence should be addressed.
Received: 31 January 2018 / Revised: 19 February 2018 / Accepted: 26 February 2018 / Published: 28 February 2018
(This article belongs to the Special Issue Role of Genomics in the Management of Hypertension)
View Full-Text   |   Download PDF [285 KB, uploaded 28 February 2018]   |  

Abstract

Worldwide, hypertension still represents a serious health burden with nine million people dying as a consequence of hypertension-related complications. Essential hypertension is a complex trait supported by multifactorial genetic inheritance together with environmental factors. The heritability of blood pressure (BP) is estimated to be 30–50%. A great effort was made to find genetic variants affecting BP levels through Genome-Wide Association Studies (GWAS). This approach relies on the “common disease–common variant” hypothesis and led to the identification of multiple genetic variants which explain, in aggregate, only 2–3% of the genetic variance of hypertension. Part of the missing genetic information could be caused by variants too rare to be detected by GWAS. The use of exome chips and Next-Generation Sequencing facilitated the discovery of causative variants. Here, we report the advances in the detection of novel rare variants, genes, and/or pathways through the most promising approaches, and the recent statistical tests that have emerged to handle rare variants. We also discuss the need to further support rare novel variants with replication studies within larger consortia and with deeper functional studies to better understand how new genes might improve patient care and the stratification of the response to antihypertensive treatments. View Full-Text
Keywords: essential hypertension; blood pressure; genome-wide association studies; exome microarray; next-generation sequencing; rare variants; rare-variants association testing; burden test; sequence kernel association test essential hypertension; blood pressure; genome-wide association studies; exome microarray; next-generation sequencing; rare variants; rare-variants association testing; burden test; sequence kernel association test
Figures

Graphical abstract

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. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Russo, A.; Di Gaetano, C.; Cugliari, G.; Matullo, G. Advances in the Genetics of Hypertension: The Effect of Rare Variants. Int. J. Mol. Sci. 2018, 19, 688.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top