title: A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians.
abstract: 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.
authors.affiliation: Human Genetics, Genome Institute of Singapore, 60 Biopolis Street, Singapore. pnge@gis.a-star.edu.sg
authors.forename: Eileen
authors.initials: E
authors.lastname: Png
authors.forename: Bachti
authors.initials: B
authors.lastname: Alisjahbana
authors.forename: Edhyana
authors.initials: E
authors.lastname: Sahiratmadja
authors.forename: Sangkot
authors.initials: S
authors.lastname: Marzuki
authors.forename: Ron
authors.initials: R
authors.lastname: Nelwan
authors.forename: Yanina
authors.initials: Y
authors.lastname: Balabanova
authors.forename: Vladyslav
authors.initials: V
authors.lastname: Nikolayevskyy
authors.forename: Francis
authors.initials: F
authors.lastname: Drobniewski
authors.forename: Sergey
authors.initials: S
authors.lastname: Nejentsev
authors.forename: Iskandar
authors.initials: I
authors.lastname: Adnan
authors.forename: Esther
authors.initials: E
authors.lastname: van de Vosse
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.forename: Reinout
authors.initials: R
authors.lastname: van Crevel
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Mark
authors.initials: M
authors.lastname: Seielstad
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D007214:Indonesia; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014397:Tuberculosis, Pulmonary / Q000235:genetics*; D055815:Young Adult