Dataset Information

Genetic risk scores for cardiometabolic traits in sub-Saharan African populations.

ABSTRACT:

Background

There is growing support for the use of genetic risk scores (GRS) in routine clinical settings. Due to the limited diversity of current genomic discovery samples, there are concerns that the predictive power of GRS will be limited in non-European ancestry populations. GRS for cardiometabolic traits were evaluated in sub-Saharan Africans in comparison with African Americans and European Americans.

Methods

We evaluated the predictive utility of GRS for 12 cardiometabolic traits in sub-Saharan Africans (AF; n = 5200), African Americans (AA; n = 9139) and European Americans (EUR; n = 9594). GRS were constructed as weighted sums of the number of risk alleles. Predictive utility was assessed using the additional phenotypic variance explained and the increase in discriminatory ability over traditional risk factors [age, sex and body mass index (BMI)], with adjustment for ancestry-derived principal components.

Results

Across all traits, GRS showed up to a 5-fold and 20-fold greater predictive utility in EUR relative to AA and AF, respectively. Predictive utility was most consistent for lipid traits, with percentage increase in explained variation attributable to GRS ranging from 10.6% to 127.1% among EUR, 26.6% to 65.8% among AA and 2.4% to 37.5% among AF. These differences were recapitulated in the discriminatory power, whereby the predictive utility of GRS was 4-fold greater in EUR relative to AA and up to 44-fold greater in EUR relative to AF. Obesity and blood pressure traits showed a similar pattern of greater predictive utility among EUR.

Conclusions

This work demonstrates the poorer performance of GRS in AF and highlights the need to improve representation of multiple ethnic populations in genomic studies to ensure equitable clinical translation of GRS.

SUBMITTER: Ekoru K

PROVIDER: S-EPMC8407873 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background and objectivesRecessive inheritance of African-specific APOL1 kidney risk variants is associated with higher risk of nondiabetic kidney disease, progression to kidney failure, and early-onset albuminuria that precedes eGFR decline. The effect of APOL1 risk variants on kidney disease in continental Africans is understudied. Objectives of this study were to determine APOL1 risk allele prevalence and associations between APOL1 genotypes and kidney disease in West, East, and South Africa.Design, setting, participants, & measurementsThis cross-sectional population-based study in four African countries included 10,769 participants largely aged 40-60 years with sociodemographic and health information, anthropometry data, and blood and urine tests for biomarkers of kidney disease. APOL1 risk alleles were imputed from the H3Africa genotyping array, APOL1 risk allele and genotype frequencies were determined, and genetic associations were assessed for kidney disease. Kidney disease was defined as the presence of eGFR <60 ml/min per 1.73 m2, albuminuria, or a composite end point including eGFR <60 ml/min per 1.73 m2 and/or albuminuria.ResultsHigh G1 allele frequencies occurred in South and West Africa (approximately 7%-13%). G2 allele frequencies were highest in South Africa (15%-24%), followed by West Africa (9%-12%). Associations between APOL1 risk variants and albuminuria were significant for recessive (odds ratio, 1.63; 95% confidence interval, 1.25 to 2.12) and additive (odds ratio, 1.39; 95% confidence interval, 1.09 to 1.76) models. Associations were stronger for APOL1 G1/G1 genotypes versus G0/G0 (odds ratio, 3.87; 95% confidence interval, 2.16 to 6.93) compared with either G2/G2 (odds ratio, 1.65; 95% confidence interval, 1.09 to 2.51) or G1/G2 (odds ratio, 1.24; 95% confidence interval, 0.83 to 1.87). No association between APOL1 risk variants and eGFR <60 ml/min per 1.73 m2 was observed.ConclusionsAPOL1 G1 and G2 alleles and high-risk genotype frequencies differed between and within West and South Africa and were almost absent from East Africa. APOL1 risk variants were associated with albuminuria but not eGFR <60 ml/min per 1.73 m2. There may be differential effects of homozygous G1 and G2 genotypes on albuminuria that require further investigation.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_05_16_CJN14321121.mp3.