TY - JOUR
KW - Receptors, Interleukin
KW - Receptor-Interacting Protein Serine-Threonine Kinase 2
KW - rab GTP-Binding Proteins
KW - Principal Component Analysis
KW - Polymorphism, Single Nucleotide
KW - Nod2 Signaling Adaptor Protein
KW - Middle Aged
KW - Male
KW - Linkage Disequilibrium
KW - leprosy
KW - Humans
KW - Haplotypes
KW - Genome-Wide Association Study
KW - Genetic Predisposition to Disease
KW - Female
KW - Epistasis, Genetic
KW - Chromosomes, Human, Pair 11
KW - Case-Control Studies
KW - Aged
AU - Zhang F
AU - Liu H
AU - Chen S
AU - Low H
AU - Sun L
AU - Cui Y
AU - Chu T
AU - Li Y
AU - Fu X
AU - Yu Y
AU - Yu G
AU - Shi B
AU - Tian H
AU - Liu D
AU - Yu X
AU - Li J
AU - Lu N
AU - Bao F
AU - Yuan C
AU - Liu J
AU - Liu H
AU - Zhang L
AU - Sun Y
AU - Chen M
AU - Yang Q
AU - Yang H
AU - Yang R
AU - Zhang L
AU - Wang Q
AU - Liu H
AU - Zuo F
AU - Zhang H
AU - Khor CC
AU - Hibberd ML
AU - Yang S
AU - Liu J
AU - Zhang X
AB - <p>We performed a genome-wide association study with 706 individuals with leprosy and 5,581 control individuals and replicated the top 24 SNPs in three independent replication samples, including a total of 3,301 individuals with leprosy and 5,299 control individuals from China. Two loci not previously associated with the disease were identified with genome-wide significance: rs2275606 (combined P = 3.94 × 10(-14), OR = 1.30) on 6q24.3 and rs3762318 (combined P = 3.27 × 10(-11), OR = 0.69) on 1p31.3. These associations implicate IL23R and RAB32 as new susceptibility genes for leprosy. Furthermore, we identified evidence of interaction between the NOD2 and RIPK2 loci, which is consistent with the biological association of the proteins encoded by these genes (NOD2-RIPK2 complex) in activating the NF-κB pathway as a part of the host defense response to infection. Our findings have expanded the biological functions of IL23R by uncovering its involvement in infectious disease susceptibility and suggest a potential involvement of autophagocytosis in leprosy pathogenesis. The IL23R association supports previous observations of the marked overlap of susceptibility genes for leprosy and Crohn's disease, implying common pathogenesis mechanisms.</p>

BT - Nature genetics
C1 - <p>http://www.ncbi.nlm.nih.gov/pubmed/22019778?dopt=Abstract</p>

DO - 10.1038/ng.973
IS - 12
J2 - Nat. Genet.
LA - eng
N2 - <p>We performed a genome-wide association study with 706 individuals with leprosy and 5,581 control individuals and replicated the top 24 SNPs in three independent replication samples, including a total of 3,301 individuals with leprosy and 5,299 control individuals from China. Two loci not previously associated with the disease were identified with genome-wide significance: rs2275606 (combined P = 3.94 × 10(-14), OR = 1.30) on 6q24.3 and rs3762318 (combined P = 3.27 × 10(-11), OR = 0.69) on 1p31.3. These associations implicate IL23R and RAB32 as new susceptibility genes for leprosy. Furthermore, we identified evidence of interaction between the NOD2 and RIPK2 loci, which is consistent with the biological association of the proteins encoded by these genes (NOD2-RIPK2 complex) in activating the NF-κB pathway as a part of the host defense response to infection. Our findings have expanded the biological functions of IL23R by uncovering its involvement in infectious disease susceptibility and suggest a potential involvement of autophagocytosis in leprosy pathogenesis. The IL23R association supports previous observations of the marked overlap of susceptibility genes for leprosy and Crohn's disease, implying common pathogenesis mechanisms.</p>

PY - 2011
SP - 1247
EP - 51
T2 - Nature genetics
TI - Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy.
VL - 43
SN - 1546-1718
ER -