PLoS Genetics (Feb 2017)

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

  • 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

DOI
https://doi.org/10.1371/journal.pgen.1006637
Journal volume & issue
Vol. 13, no. 2
p. e1006637

Abstract

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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.