Autozygosity influences cardiometabolic disease-associated traits in the AWI-Gen sub-Saharan African study

Francisco C. Ceballos, Scott Hazelhurst, David W. Clark, Godfred Agongo, Gershim Asiki, Palwende R. Boua, F. Xavier Gómez-Olivé, Felistas Mashinya, Shane Norris, James F. Wilson and Michèle Ramsay ()
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Francisco C. Ceballos: Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand
Scott Hazelhurst: Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand
David W. Clark: University of Edinburgh
Godfred Agongo: Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand
Gershim Asiki: African Population and Health Research Center
Palwende R. Boua: Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand
F. Xavier Gómez-Olivé: MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand
Felistas Mashinya: Department of Pathology and Medical Science, School of Health Care Sciences, Faculty of Health Sciences, University of Limpopo
Shane Norris: Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand
James F. Wilson: University of Edinburgh
Michèle Ramsay: Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand

Nature Communications, 2020, vol. 11, issue 1, 1-8

Abstract: Abstract The analysis of the effects of autozygosity, measured as the change of the mean value of a trait among offspring of genetic relatives, reveals the existence of directional dominance or overdominance. In this study we detect evidence of the effect of autozygosity in 4 out of 13 cardiometabolic disease-associated traits using data from more than 10,000 sub-Saharan African individuals recruited from Ghana, Burkina Faso, Kenya and South Africa. The effect of autozygosity on these phenotypes is found to be sex-related, with inbreeding having a significant decreasing effect in men but a significant increasing effect in women for several traits (body mass index, subcutaneous adipose tissue, low-density lipoproteins and total cholesterol levels). Overall, the effect of inbreeding depression is more intense in men. Differential effects of inbreeding depression are also observed between study sites with different night-light intensity used as proxy for urban development. These results suggest a directional dominant genetic component mediated by environmental interactions and sex-specific differences in genetic architecture for these traits in the Africa Wits-INDEPTH partnership for Genomic Studies (AWI-Gen) cohort.

Date: 2020
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DOI: 10.1038/s41467-020-19595-y

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