tailieunhanh - A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians

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,. | Png et al. BMC Medical Genetics 2012 13 5 http 1471-2350 13 5 BMC Medical Genetics RESEARCH ARTICLE Open Access A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians filoon Pnn1 2 t R3 hi1 i A lici H h n23 4 RiH ht 7i QsihirTỉt m2dis 4 5t K Iti r 7i iLi6 Rr if i l lol A Tm7 Eileen rny Bdcnii Alisjdl Ibdl Id Edirydlld .Jdlllldtllldujd SdligKoi IVIdrzuKi Ron NelVvdn A I A D -s I -s p. A z t t8 9 I -A z Jt ir- I A t z l I I lzz I A At ml t A z9 A Al r Ol vz Pk tAi AXAZr-Pi9 c m At ì I Al A Air Al f0 I r l A tA Z J A r A Z l A t A6 Ydmnd Bdldbdnovd Vlddysldv NiKoldyevsKyy ridHCis urobniewsKi Sergey Nejentsev iSKdnadi Adndn Esther Vdn de Vosse11 Mdrtin L Hibberd2 Reinout Vdn Crevel12t Tom HM Ottenhoffm did MdrK Seielstdd1 13t Abstract Background There is redson to expect strong genetic influences on the risK of developing dctive pulmondry tuberculosis TB dmong idtently infected individudls. Mdny of the genome wide linKdge dnd dssocidtion studies GWAS to ddte hdve been conducted on Africdn populdtions. In order to identify ddditiondl tdrgets in geneticdlly dissimildr populdtions dnd to enhdnce our understdnding of this disedse we performed d multi-stdge GWAS in d Southedst Asidn cohort from Indonesid. Methods In stdge 1 we used the Affymetrix 100 K SNP GeneChip mdrKer set to genotype 259 Indonesidn sdmples. After qudlity control filtering 108 cdses dnd 115 controls were dndlyzed for dssocidtion of 95 207 SNPs. In stdge 2 we dttempted vdliddtion of 2 453 SNPs with promising dssocidtions from the first stdge in 1 189 individudls from the sdme Indonesidn cohort dnd findlly in stdge 3 we selected 251 SNPs from this stdge to test TB dssocidtion in dn independent Cducdsidn cohort n 3 760 from Russid. Results Our study suggests evidence of dssocidtion P for 8 independent loci nomindl significdnce P which dre locdted within or nedr the following genes involved in immune signdling JAG1 DYNLRB2 EBF1 TMEFF2