Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans

Palwende Romuald Boua (), Jean-Tristan Brandenburg, Ananyo Choudhury, Hermann Sorgho, Engelbert A. Nonterah, Godfred Agongo, Gershim Asiki, Lisa Micklesfield, Solomon Choma, Francesc Xavier Gómez-Olivé, Scott Hazelhurst, Halidou Tinto, Nigel J. Crowther, Christopher G. Mathew and Michèle Ramsay ()
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Palwende Romuald Boua: Centre national de la Recherche scientifique et technologique (CNRST)
Jean-Tristan Brandenburg: University of the Witwatersrand
Ananyo Choudhury: University of the Witwatersrand
Hermann Sorgho: Centre national de la Recherche scientifique et technologique (CNRST)
Engelbert A. Nonterah: Navrongo Health Research Centre, Ghana Health Service
Godfred Agongo: Navrongo Health Research Centre, Ghana Health Service
Gershim Asiki: African Population and Health Research Center
Lisa Micklesfield: University of the Witwatersrand
Solomon Choma: University of Limpopo
Francesc Xavier Gómez-Olivé: University of the Witwatersrand
Scott Hazelhurst: University of the Witwatersrand
Halidou Tinto: Centre national de la Recherche scientifique et technologique (CNRST)
Nigel J. Crowther: University of the Witwatersrand
Christopher G. Mathew: University of the Witwatersrand
Michèle Ramsay: University of the Witwatersrand

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-28276-x

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