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

Anno:

2018

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

Russo A1,2, Di Gaetano C3,4, Cugliari G5,6, Matullo G7,8.

Int J Mol Sci. 2018 Feb 28;19(3). pii: E688. doi: 10.3390/ijms19030688. PMID: 29495593

Author information

1: Department of Medical Sciences, University of Turin, 10126 Turin, Italy. alessia.russo@hugef.org.
2: Italian Institute for Genomic Medicine (IIGM, Formerly HuGeF), 10126 Turin, Italy. alessia.russo@hugef.org.
3: Department of Medical Sciences, University of Turin, 10126 Turin, Italy. cornelia.digaetano@unito.it.
4: Italian Institute for Genomic Medicine (IIGM, Formerly HuGeF), 10126 Turin, Italy. cornelia.digaetano@unito.it.
5: Department of Medical Sciences, University of Turin, 10126 Turin, Italy. giovanni.cugliari@hugef.org.
6: Italian Institute for Genomic Medicine (IIGM, Formerly HuGeF), 10126 Turin, Italy. giovanni.cugliari@hugef.org.
7: Department of Medical Sciences, University of Turin, 10126 Turin, Italy. giuseppe.matullo@unito.it.
8: Italian Institute for Genomic Medicine (IIGM, Formerly HuGeF), 10126 Turin, Italy. giuseppe.matullo@unito.it.

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.