| Title: |
Genome-wide association study of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway |
| Authors: |
Manry, Jeremy; Vincent, Quentin; Johnson, Christian; Chrabieh, Maya; Lorenzo, Lazaro; Theodorou, Ioannis; Ardant, Marie-Françoise; Marion, Estelle; Chauty, Annick; Marsollier, Laurent; Abel, Laurent; Alcaïs, Alexandre |
| Contributors: |
Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Université d’Abomey-Calavi = University of Abomey Calavi (UAC); Centre d'Immunologie et des Maladies Infectieuses (CIMI); Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); Hopital Saint-Louis AP-HP (AP-HP); Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA); Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN); Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9); Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Rockefeller University New York; ANR-16-CE12-0023,MYCOPARADOX,Dissection de l'architecture génétique des réactions paradoxales dans la Lèpre et l'Ulcère de Buruli(2016) |
| Source: |
ISSN: 2399-3642 ; Communications Biology ; https://hal.sorbonne-universite.fr/hal-02573225 ; Communications Biology, 2020, 3, pp.177. ⟨10.1038/s42003-020-0920-6⟩. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2020 |
| Subject Terms: |
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics; [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE]; [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases; [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/32313116; PUBMED: 32313116; PUBMEDCENTRAL: PMC7171125 |
| DOI: |
10.1038/s42003-020-0920-6 |
| Availability: |
https://hal.sorbonne-universite.fr/hal-02573225; https://hal.sorbonne-universite.fr/hal-02573225v1/document; https://hal.sorbonne-universite.fr/hal-02573225v1/file/s42003-020-0920-6.pdf; https://doi.org/10.1038/s42003-020-0920-6 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.F799751 |
| Database: |
BASE |