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

Jeremy Manry (1, 2) , Quentin Vincent (1, 2) , Christian Johnson (3) , Maya Chrabieh (1, 2) , Lazaro Lorenzo (2, 1) , Ioannis Theodorou (4, 5) , Marie-Françoise Ardant , Estelle Marion (6, 7) , Annick Chauty , Laurent Marsollier (6, 7) , Laurent Abel (1, 2, 8) , Alexandre Alcaïs (1, 2)

1 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
2 Hôpital Necker - Enfants Malades [AP-HP]
3 UAC - Université d’Abomey-Calavi = University of Abomey Calavi
4 CIMI - Centre d'Immunologie et des Maladies Infectieuses
5 AP-HP - Hopital Saint-Louis [AP-HP]
6 CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
7 CRCINA-ÉQUIPE 9 - Apoptosis and Tumor Progression
8 Rockefeller University [New York]

Buruli ulcer, caused by Mycobacterium ulcerans and characterized by devastating necrotizing skin lesions, is the third mycobacterial disease worldwide. 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 sample of 1524 well characterized patients and controls from rural Benin. Two-stage analyses identify two variants located within LncRNA 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, previously shown to decrease bacterial autophagy (rs2241880, P = 0.003; odds ratio = 0.31 [0.14-0.68]). Our results suggest LncRNAs and the autophagy pathway as critical factors in the development of Buruli ulcer.

Domaines: Génétique humaine; Génétique des populations [q-bio.PE]; Maladies infectieuses; Dermatologie

Jeremy Manry, Quentin Vincent, Christian Johnson, Maya Chrabieh, Lazaro Lorenzo, et al.. Genome-wide association study of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway. Communications Biology, 2020, 3, pp.177. ⟨10.1038/s42003-020-0920-6⟩. ⟨hal-02573225⟩