Genome-wide association study of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway.
Jérémy ManryQuentin B VincentChristian JohnsonMaya ChrabiehLazaro LorenzoIoannis TheodorouMarie-Françoise ArdantEstelle MarionAnnick ChautyLaurent MarsollierLaurent AbelAlexandre AlcaïsPublished in: Communications biology (2020)
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.
Keyphrases
- genome wide association study
- cell death
- endoplasmic reticulum stress
- oxidative stress
- signaling pathway
- mycobacterium tuberculosis
- end stage renal disease
- long non coding rna
- south africa
- newly diagnosed
- chronic kidney disease
- ejection fraction
- long noncoding rna
- cell proliferation
- gene expression
- genome wide identification
- prognostic factors
- intellectual disability
- copy number
- genome wide analysis
- genome wide
- dna methylation
- wound healing
- transcription factor
- patient reported
- bioinformatics analysis