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Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans
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Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans
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Journal Article
Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans
2022
Overview
Atherosclerosis precedes the onset of clinical manifestations of cardiovascular diseases (CVDs). We used carotid intima-media thickness (cIMT) to investigate genetic susceptibility to atherosclerosis in 7894 unrelated adults (3963 women, 3931 men; 40 to 60 years) resident in four sub-Saharan African countries. cIMT was measured by ultrasound and genotyping was performed on the H3Africa SNP Array. Two new African-specific genome-wide significant loci for mean-max cIMT,
SIRPA
(p = 4.7E-08), and
FBXL17
(p = 2.5E-08), were identified. Sex-stratified analysis revealed associations with one male-specific locus,
SNX29
(p = 6.3E-09), and two female-specific loci,
LARP6
(p = 2.4E-09) and
PROK1
(p = 1.0E-08). We replicate previous cIMT associations with different lead SNPs in linkage disequilibrium with SNPs primarily identified in European populations. Our study find significant enrichment for genes involved in oestrogen response from female-specific signals. The genes identified show biological relevance to atherosclerosis and/or CVDs, sex-differences and transferability of signals from non-African studies.
Genetic studies of disease-relevant traits have mostly been performed on European populations. Here, the authors perform a genome-wide association study for carotid intima-media thickness, in sub-Saharan African samples, finding population-specific and sex-specific loci.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Adult
/ Cardiovascular Diseases - genetics
/ Carotid Intima-Media Thickness - statistics & numerical data
/ Female
/ Females
/ Gastrointestinal Hormones - genetics
/ Genes
/ Genetic Predisposition to Disease - genetics
/ Genome-wide association studies
/ Genomes
/ Humanities and Social Sciences
/ Humans
/ Loci
/ Male
/ Men
/ Polymorphism, Single Nucleotide - genetics
/ Ribonucleoproteins - genetics
/ Science
/ Sex
/ Single-nucleotide polymorphism
/ Vascular Endothelial Growth Factor, Endocrine-Gland-Derived - genetics
