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

Author

Listed:
  • Palwende Romuald Boua

    (Centre national de la Recherche scientifique et technologique (CNRST)
    University of the Witwatersrand
    University of the Witwatersrand)

  • 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
    University Medical Centre, Utrecht University)

  • Godfred Agongo

    (Navrongo Health Research Centre, Ghana Health Service
    C.K. Tedam University of Technology and Applied Sciences)

  • 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
    University of the Witwatersrand
    Faculty of Life Sciences and Medicine, King’s College London)

  • Michèle Ramsay

    (University of the Witwatersrand
    University of the Witwatersrand)

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.

Suggested Citation

  • Palwende Romuald Boua & Jean-Tristan Brandenburg & Ananyo Choudhury & Hermann Sorgho & Engelbert A. Nonterah & Godfred Agongo & Gershim Asiki & Lisa Micklesfield & Solomon Choma & Francesc Xavier Góme, 2022. "Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28276-x
    DOI: 10.1038/s41467-022-28276-x
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    References listed on IDEAS

    as
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    2. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    3. Anshul Kundaje & Wouter Meuleman & Jason Ernst & Misha Bilenky & Angela Yen & Alireza Heravi-Moussavi & Pouya Kheradpour & Zhizhuo Zhang & Jianrong Wang & Michael J. Ziller & Viren Amin & John W. Whit, 2015. "Integrative analysis of 111 reference human epigenomes," Nature, Nature, vol. 518(7539), pages 317-330, February.
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