Genome-wide association study of Buruli ulcer in rural Benin

Abstract Buruli ulcer, caused by Mycobacterium ulcerans , is the third mycobacterial disease worldwide characterized by devastating necrotizing skin lesions. The role of host genetics in susceptibility to Buruli ulcer has long been suggested. We conduct the first genome-wide association study of Buruli ulcer on a combined sample of 1,524 well characterized patients and controls from rural Benin. Two-stage analyses identify two novel associated loci located within lincRNA genes: rs9814705 in ENSG00000240095 . 1 ( P = 2.85×10 −7 ; odds ratio = 1.80 [1.43-2.27]), and rs76647377 in LINC01622 ( P = 9.85×10 −8 ; hazard ratio = 0.41 [0.28-0.60]). Furthermore, we replicate the protective effect of allele G of a missense variant located in ATG16L1 , and previously shown to decrease bacterial autophagy (rs2241880, P = 0.003; odds ratio = 0.31 [0.14-0.68]). Our results suggest lincRNAs and the autophagy pathway as critical factors in the development of Buruli ulcer.