Genome-wide association study of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway

• DOI: 10.1038/s42003-020-0920-6
• Publication Date: 2020-04-20T10:03:19Z
• Authors: Jeremy Manry; Quentin B. Vincent; Christian Johnson; Maya Chrabieh; Lazaro Lorenzo; Ioannis Theodorou; Marie-Françoise A...; Estelle Marion; Annick Chauty; Laurent Marsollier; Laurent Abel; Alexandre Alcaïs
• Keywords: Buruli ulcer; Mycobacterium ulcerans; ATG16L1; Genome-wide Association Study

Abstract Buruli ulcer, caused by Mycobacterium ulcerans and characterized devastating necrotizing skin lesions, is the third mycobacterial disease worldwide. The role of host genetics in susceptibility to ulcer has long been suggested. We conduct first genome-wide association study on a sample 1524 well patients controls from rural Benin. Two-stage analyses identify two variants located within LncRNA genes: rs9814705 ENSG00000240095.1 ( P = 2.85 × 10 −7 ; odds ratio 1.80 [1.43–2.27]), rs76647377 LINC01622 9.85 −8 hazard 0.41 [0.28–0.60]). Furthermore, we replicate protective effect allele G missense variant ATG16L1 , previously shown decrease bacterial autophagy (rs2241880, 0.003; 0.31 [0.14–0.68]). Our results suggest LncRNAs pathway as critical factors development ulcer.