What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Hypertension and blood pressure traits (n=10775). Intervention: Genetic variants (SNPs) vs. Reference alleles. Primary outcome: Genome-wide significant association with systolic blood pressure (rs77846204 near P2RY1) (Beta -1.99, p=4.95E-08).

December 16, 2023Open Access

Genome-wide association study meta-analysis of blood pressure traits and hypertension in sub-Saharan African populations: an AWI-Gen study

SSSurina SinghUniversity of the Witwatersrand ACAnanyo ChoudhuryNational Health Laboratory Service SHScott HazelhurstUniversity of the Witwatersrand

Key Result

A GWAS meta-analysis of 10,775 sub-Saharan Africans identified two novel genome-wide significant signals: systolic blood pressure near P2RY1 (p=4.95E-08) and pulse pressure near LINC01256 (p=1.76E-08).

Study Design

Type

Meta-Analysis (n=10,775)

Multicenter

Yes

Structured PICO

Population

10,775 adults from sub-Saharan Africa assessed for genetic associations with blood pressure traits and hypertension.

Outcome

Blood pressure-related traits (systolic and diastolic BP, pulse pressure, mean-arterial pressure and hypertension)surrogate

This GWAS meta-analysis identifies novel genetic variants associated with blood pressure traits in sub-Saharan African populations, highlighting the limited transferability of polygenic risk scores derived from other ancestries.

Main Result

Mean Difference: -1.99

p-value: p=4.95E-08

Limitations

Modest sample size with limited power to identify associations with markers with low minor allele frequency and small effect sizes
Lack of multiple large African-ancestry datasets for replication
Lack of knowledge of related hypertension co-factors such as diabetes medication in some cohorts

Abstract

Most hypertension-related genome-wide association studies (GWASs) focus on non-African populations, despite hypertension (a major risk factor for cardiovascular disease) being highly prevalent in Africa. The AWI-Gen study GWAS meta-analysis for blood pressure (BP)-related traits (systolic and diastolic BP, pulse pressure, mean-arterial pressure and hypertension) from three sub-Saharan African geographic regions (N = 10,775), identifies two novel genome-wide significant signals (p < 5E-08): systolic BP near P2RY1 (rs77846204; intergenic variant, p = 4.95E-08) and pulse pressure near LINC01256 (rs80141533; intergenic variant, p = 1.76E-08). No genome-wide signals are detected for the AWI-Gen GWAS meta-analysis with previous African-ancestry GWASs (UK Biobank (African), Uganda Genome Resource). Suggestive signals (p < 5E-06) are observed for all traits, with 29 SNPs associating with more than one trait and several replicating known associations. Polygenic risk scores (PRSs) developed from studies on different ancestries have limited transferability, with multi-ancestry PRS providing better prediction. This study provides insights into the genetics of BP variation in African populations.

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