A genome wide association study identifies a lncRna as risk factor for pathological inflammatory responses in leprosy

by Vinicius M. Fava, Jeremy Manry, Aurélie Cobat, Marianna Orlova, Nguyen Van Thuc, Milton O. Moraes, Carolinne Sales-Marques, Mariane M. A. Stefani, Ana Carla P. Latini, Andrea F. Belone, Vu Hong Thai, Laurent Abel, Alexandre Alcaïs, Erwin Schurr

Leprosy Type-1 Reactions (T1Rs) are pathological inflammatory responses that afflict a sub-group of leprosy patients and result in peripheral nerve damage. Here, we employed a family-based GWAS in 221 families with 229 T1R-affect offspring with stepwise replication to identify risk factors for T1R. We discovered, replicated and validated T1R-specific associations with SNPs located in chromosome region 10p21.2. Combined analysis across the three independent samples resulted in strong evidence of association of rs1875147 with T1R (p = 4.5x10^-8; OR = 1.54, 95% CI = 1.32–1.80). The T1R-risk locus was restricted to a lncRNA-encoding genomic interval with rs1875147 being an eQTL for the lncRNA. Since a genetic overlap between leprosy and inflammatory bowel disease (IBD) has been detected, we evaluated if the shared genetic control could be traced to the T1R endophenotype. Employing the results of a recent IBD GWAS meta-analysis we found that 10.6% of IBD SNPs available in our dataset shared a common risk-allele with T1R (p = 2.4x10^-4). This finding points to a substantial overlap in the genetic control of clinically diverse inflammatory disorders.

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