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

• Published in: Nature communications Vol. 11; no. 1; pp. 5754 - 8
• Main Authors: Ceballos, Francisco C., Hazelhurst, Scott, Clark, David W., Agongo, Godfred, Asiki, Gershim, Boua, Palwende R., Xavier Gómez-Olivé, F., Mashinya, Felistas, Norris, Shane, Wilson, James F., Ramsay, Michèle
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13-11-2020; Nature Publishing Group; Nature Portfolio
• Subjects: 45/43; 631/208/1397; 631/208/205/2138; 692/699/1702/393; 692/699/75; Adipose tissue; Africa South of the Sahara - epidemiology; Body mass; Body mass index; Body size; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - genetics; Cholesterol; Consanguinity; Disease; Female; Genes, Recessive; Genetics; Genome, Human; Genome-Wide Association Study; Health sciences; Homozygote; Humanities and Social Sciences; Humans; Inbreeding; Inbreeding Depression; Light; Light intensity; Lipoproteins; Luminous intensity; Male; Medical research; Men; multidisciplinary; Obesity - epidemiology; Obesity - genetics; Offspring; Phenotype; Phenotypes; Public health; Science; Science (multidisciplinary); Sex; Sex Factors; Triglycerides; Urban development; Urbanization; Womens health; Africa South of the Sahara; Africa
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-19595-y

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.
The prevalence of cardiometabolic diseases (CMDs) is increasing rapidly across Africa. Here, the authors investigate autozygosity in CMD-associated traits in over 10,000 sub-Saharan African individuals, showing these traits are influenced by sex-specific inbreeding depression and environmental interactions.