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

Autor: Ceballos FC; Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Hazelhurst S; Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; School of Electrical & Information Engineering, University of the Witwatersrand, Johannesburg, South Africa., Clark DW; Centre for Global Health Research, Usher Institute, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK., Agongo G; Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Navrongo Health Research Centre, Navrongo, Ghana., Asiki G; African Population and Health Research Center, Nairobi, Kenya., Boua PR; Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Faculty of Health Sciences University of the Witwatersrand, Division of Human Genetics, National Health Laboratory Service and School of Pathology, Johannesburg, South Africa.; Clinical Research Unit of Nanoro, Institut de Recherche en Sciences de la Santé, Nanoro, Burkina Faso., Xavier Gómez-Olivé F; MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Mashinya F; Department of Pathology and Medical Science, School of Health Care Sciences, Faculty of Health Sciences, University of Limpopo, Polokwane, South Africa., Norris S; Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Faculty of Health Sciences University of the Witwatersrand, Division of Human Genetics, National Health Laboratory Service and School of Pathology, Johannesburg, South Africa., Wilson JF; Centre for Global Health Research, Usher Institute, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK.; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK., Ramsay M; Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Michele.Ramsay@wits.ac.za.; Faculty of Health Sciences University of the Witwatersrand, Division of Human Genetics, National Health Laboratory Service and School of Pathology, Johannesburg, South Africa. Michele.Ramsay@wits.ac.za.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Nov 13; Vol. 11 (1), pp. 5754. Date of Electronic Publication: 2020 Nov 13.
DOI: 10.1038/s41467-020-19595-y
Abstrakt: 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.
Databáze: MEDLINE