Brief Overview of a Decade of Genome-Wide Association Studies on Primary Hypertension

Abstract

Primary hypertension is widely believed to be a complex polygenic disorder with the manifestation influenced by the interactions of genomic and environmental factors making identification of susceptibility genes a major challenge. With major advancement in high-throughput genotyping technology, genome-wide association study (GWAS) has become a powerful tool for researchers studying genetically complex diseases. GWASs work through revealing links between DNA sequence variation and a disease or trait with biomedical importance. The human genome is a very long DNA sequence which consists of billions of nucleotides arranged in a unique way. A single base-pair change in the DNA sequence is known as a single nucleotide polymorphism (SNP). With the help of modern genotyping techniques such as chip-based genotyping arrays, thousands of SNPs can be genotyped easily. Large-scale GWASs, in which more than half a million of common SNPs are genotyped and analyzed for disease association in hundreds of thousands of cases and controls, have been broadly successful in identifying SNPs associated with heart diseases, diabetes, autoimmune diseases, and psychiatric disorders. It is however still debatable whether GWAS is the best approach for hypertension. The following is a brief overview on the outcomes of a decade of GWASs on primary hypertension.

A Variant in the Nicotinic Acetylcholine Receptor Alpha 3 Subunit Gene Is Associated With Hypertension Risks in Hypogonadic Patients

“…CHRNA3 SNVs have not been found to be significantly associated with hypertension risks in many genomewide association studies (Wellcome Trust Case Control Consortium, 2007;Adeyemo et al, 2009;Levy et al, 2009;Org et al, 2009;Hiura et al, 2010;Padmanabhan et al, 2010;International Consortium for Blood Pressure Genome-Wide Association Studies et al, 2011;Slavin et al, 2011;Guo et al, 2012). However, testosterone levels are not stratified in these studies.…”

Genome-wide Association Study Meta-analysis of Blood Pressure Traits and Hypertension in Sub-Saharan African Populations: An AWI-Gen Study

“…Early GWAS studies outlined the complexity of studying BP-related traits and emphasised the importance of large sample sizes to enable the detection of genetic associations 19,20 . Large-scale GWAS discovery meta-analyses have shown signi cant genetic associations with BP and HTN 16,21,22 . The largest BP GWAS to date by Evangelou, et al 22 included over 1 million individuals of European ancestry from the UK Biobank (UKBB) and the International Consortium of Blood Pressure (ICBP), identifying 535 BP-related loci.…”

“…Genome-wide association studies (GWASs) have explained only a modest proportion of the genetic heritability (3-6%) for blood pressure (BP) and HTN 16 . The GWAS Catalog 17 18 includes data from the rst BP/HTN case-control studies conducted in 2007 for HTN 19 and for BP as a quantitative trait 20 .…”

“…Only a small number of GWAS for genetic associations with BP and HTN have been performed on the African continent. Despite HTN being highly prevalent in Africa 23 , most studies have focused on the European populations 16 . Studies based on African-ancestry populations comprise mainly of African American (AA) populations [24][25][26][27][28] , with the rst GWAS for HTN in AA conducted in 2009 by Adeyemo, et al 29 .…”

Systematic Review of Genomic Associations with Blood Pressure and Hypertension in Populations with African-Ancestry

“…The importance of increasing the representation of diverse populations in genomic research, including Africans, has been addressed in many studies ( Ramsay et al, 2016 ; Martin et al, 2018 ; Popejoy et al, 2018 ; Bentley et al, 2020 ). Most GWAS studies have focused on the European ancestry populations ( Azam and Azizan, 2018 ), and studies based on African-ancestry participants comprise mainly African Americans (AAs) ( Manolio et al, 2009 ; Franceschini et al, 2013 ; Franceschini et al, 2016 ; Taylor et al, 2016 ; Liang et al, 2017 ). The first GWAS for HTN in AAs was conducted by Adeyemo et al (2009) .…”