Genome-wide high-density SNP linkage search for glioma susceptibility loci: Results from the gliogene consortium

Sanjay Shete, Ching C. Lau, Richard S. Houlston, Elizabeth B. Claus, Jill Barnholtz-Sloan, Rose Lai, Dora Il'yasova, Joellen Schildkraut, Siegal Sadetzki, Christoffer Johansen, Jonine L. Bernstein, Sara H. Olson, Robert B. Jenkins, Ping Yang, Nicholas A. Vick, Margaret Wrensch, Faith G. Davis, Bridget J. McCarthy, Eastwood Hon Chiu Leung, Caleb DavisRita Cheng, Fay J. Hosking, Georgina N. Armstrong, Yanhong Liu, Robert K. Yu, Roger Henriksson, Beatrice S. Melin, Melissa L. Bondy, Christopher Amos, Kenneth D. Aldape, Mark R. Gilbert, Jeffrey Weinberg, Chris Man, Rudy Guerra, Sivashankarappa Gurusiddappa, Michael E. Scheurer, Lindsay Robertson, Elli Papaemmanuil, Andrew E. Sloan, Gene Barnett, Karen Devine, Yingli Wolinsky, Erika Florendo, Delcia Rivas, Christina Corpuz, Galit Hirsh Yechezkel, Revital Bar Sade Bruchim, Lili Aslanov, Hanne Bødtcher, Michael Kosteljanetz, Helle Broholm, Erica Schubert, Lisa DeAngelis, Amanda Rynearson, Ulrika Andersson, Thomas Brännström, John Wiencke, Joe Wiemels, Lucie McCoy

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32 and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P=0.008) and the Z-score of 1.47 (P=0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P = 0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma.

Original languageEnglish (US)
Pages (from-to)7568-7575
Number of pages8
JournalCancer research
Issue number24
StatePublished - Dec 15 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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