A Genome-Wide Association Study Reveals Novel Genetic Markers Associated with Human African Trypanosomiasis

Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense cause human African trypanosomiasis (HAT), a neglected tropical disease that constitutes an important public health issue in sub-Saharan Africa. In the absence of a vaccine, only chemotherapy and vector control has been used to combat the disease. Environmental factors, such as exposure to infected tsetse files, and genetic factors such as variants in the APOL1 gene have been shown to contribute to the risk of developing HAT. However, the known factors only explain a small part of the risk of developing trypanosomiasis. We have undertaken a genome wide association study (GWAS) using 3813 samples from T. b. gambiense and T.b. rhodesiense HAT foci in Guinea, Cote dIvoire, Cameroon, DRC, Malawi and Uganda. 2141 samples were genotyped on the H3Africa SNP chip followed by a genotyping a validation cohort of an additional 1,627 samples at candidate loci. After the primary and validation studies we identified a novel locus near SMOC2 with genome-wide significance. We also identified suggestive associations near NXN, NTNG1 and NCKAP5 that have stronger associations with disease susceptibility than the APOL1 loci that has been previously identified by hypothesis driven approaches. These genes offer new entry points for future studies of the underlying genetic mechanisms of HAT.