TY - JOUR
T1 - A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians
AU - Png, Eileen
AU - Alisjahbana, Bachti
AU - Sahiratmadja, Edhyana
AU - Marzuki, Sangkot
AU - Nelwan, Ron
AU - Balabanova, Yanina
AU - Nikolayevskyy, Vladyslav
AU - Drobniewski, Francis
AU - Nejentsev, Sergey
AU - Adnan, Iskandar
AU - van de Vosse, Esther
AU - Hibberd, Martin L.
AU - van Crevel, Reinout
AU - Ottenhoff, Tom H.M.
AU - Seielstad, Mark
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/1/13
Y1 - 2012/1/13
N2 - Background: There is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals. Many of the genome wide linkage and association studies (GWAS) to date have been conducted on African populations. In order to identify additional targets in genetically dissimilar populations, and to enhance our understanding of this disease, we performed a multi-stage GWAS in a Southeast Asian cohort from Indonesia.Methods: In stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian samples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In stage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals from the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB association in an independent Caucasian cohort (n = 3,760) from Russia.Results: Our study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal significance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4.Conclusions: Mechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may suggest novel pathways involved in the host containment of infection with TB.
AB - Background: There is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals. Many of the genome wide linkage and association studies (GWAS) to date have been conducted on African populations. In order to identify additional targets in genetically dissimilar populations, and to enhance our understanding of this disease, we performed a multi-stage GWAS in a Southeast Asian cohort from Indonesia.Methods: In stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian samples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In stage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals from the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB association in an independent Caucasian cohort (n = 3,760) from Russia.Results: Our study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal significance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4.Conclusions: Mechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may suggest novel pathways involved in the host containment of infection with TB.
UR - http://www.scopus.com/inward/record.url?scp=84855718039&partnerID=8YFLogxK
U2 - 10.1186/1471-2350-13-5
DO - 10.1186/1471-2350-13-5
M3 - Article
C2 - 22239941
AN - SCOPUS:84855718039
SN - 1471-2350
VL - 13
JO - BMC Medical Genetics
JF - BMC Medical Genetics
M1 - 5
ER -
