Genome-wide association study of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway
Open Access
- 20 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Communications Biology
- Vol. 3 (1), 1-10
- https://doi.org/10.1038/s42003-020-0920-6
Abstract
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.Funding Information
- Agence Nationale de la Recherche (ANR-10-IAHU-01, ANR 17 BSV3 0013 01, ANR-10-IAHU-01, ANR 12 BSV3 0013 01, ANR 17 BSV3 0013 01, ANR-10-IAHU-01)
- Fondation pour la Recherche Médicale (DMI20091117308)
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