Studies assessing genetic diversity in global populations are important to understand the impact of genetic variation on disease risk, but limited numbers of genome-wide association studies (GWAS) have been performed in non-European populations. Genetic variation is higher in African populations than in European populations, which suggests more opportunities for discovery per individual in populations with African ancestry. A new paper in Cell provides the largest whole-genome sequence data set in an African population to date and shows that genetic causes of disease can differ between African and European populations.

Credit: P. Morgan/Springer Nature Limited

Gurdasani et al. collected and analysed genome-wide data from approximately 6,400 individuals in a rural Ugandan community, obtaining whole-genome sequences from nearly 2,000 of them. In addition, data from nearly 8,000 individuals from Ghana, Kenya, Nigeria and South Africa were analysed. An electronic questionnaire was used to collect information on demographics and non-communicable diseases, and physical attributes, such as height, weight and blood pressure, and serum levels of lipids and haemoglobin A1c (HbA1c) were measured.

Ugandan genomes were a mixture of many ancestries, including ancient East African populations and Eurasian genomes, indicating a complex history of migration into the region. As expected, the authors found that Africans had higher levels of genetic variation than other continental populations.

In a GWAS of 34 cardiometabolic traits in up to ~14,000 individuals from the African populations, the researchers identified new genetic associations between variants unique to Africans (or rare in non-Africans) and blood, liver function and glucose-related traits. For example, a novel association was identified between a deletion known to cause α-thalassaemia in African individuals and HbA1c levels. The deletion is present in 22% of Africans and protective against severe malaria. As HbA1c levels are often used to diagnose diabetes mellitus, the authors say its utility as a diagnostic test in African populations needs to be evaluated.

Height was less genetically determined in the rural Ugandan population than in Europeans, perhaps due to nutritional deficits that attenuate the effects of genetic variance on height. By contrast, LDL cholesterol levels were more genetically determined in Ugandans than in Europeans, potentially as a result of increased levels of obesity that reduce the influence of genetic factors on LDL cholesterol levels.

Africans had higher levels of genetic variation than other continental populations

“This study confirms that genetic causes of disease may be different in Africans and provides opportunities to identify new genes associated with disease that would not be identified in European studies,” says Gurdasani. “This kind of research will allow us to identify new targets for therapies that could potentially be useful for all populations.”