Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.


Melin BS, Barnholtz-Sloan JS, Wrensch MR, Johansen C, Il’yasova D, Kinnersley B, Ostrom QT, Labreche K, Chen Y, Armstrong G, Liu Y, Eckel-Passow JE, Decker PA, Labussière M, Idbaih A, Hoang-Xuan K, Di Stefano AL, Mokhtari K, Delattre JY, Broderick P, Galan P, Gousias K, Schramm J, Schoemaker MJ, Fleming SJ, Herms S, Heilmann S, Nöthen MM, Wichmann HE, Schreiber S, Swerdlow A, Lathrop M, Simon M, Sanson M, Andersson U, Rajaraman P, Chanock S, Linet M, Wang Z, Yeager M, , Wiencke JK, Hansen H, McCoy L, Rice T, Kosel ML, Sicotte H, Amos CI, Bernstein JL, Davis F, Lachance D, Lau C, Merrell RT, Shildkraut J, Ali-Osman F, Sadetzki S, Scheurer M, Shete S, Lai RK, Claus EB, Olson SH, Jenkins RB, Houlston RS, Bondy ML,.

Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P 2.04 10(-9), odds ratio (OR) 1.22), 11q14.1 (rs11233250; P 9.95 10(-10), OR 1.24), 16p13.3 (rs2562152; P 1.93 10(-8), OR 1.21), 16q12.1 (rs10852606; P 1.29 10(-11), OR 1.18) and 22q13.1 (rs2235573; P 1.76 10(-10), OR 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P 3.34 10(-9), OR 1.19), 1q44 (rs12076373; P 2.63 10(-10), OR 1.23), 2q33.3 (rs7572263; P 2.18 10(-10), OR 1.20), 3p14.1 (rs11706832; P 7.66 10(-9), OR 1.15), 10q24.33 (rs11598018; P 3.39 10(-8), OR 1.14), 11q21 (rs7107785; P 3.87 10(-10), OR 1.16), 14q12 (rs10131032; P 5.07 10(-11), OR 1.33) and 16p13.3 (rs3751667; P 2.61 10(-9), OR 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.

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Will Bush

Will Bush

William S. Bush, Ph.D., is a human geneticist and bioinformatician, and Assistant Professor within the Cleveland Institute for Computational Biology and the Department of Population and Quantitative Health Sciences at Case Western Reserve University.