Genome-wide high-density SNP linkage search for glioma susceptibility loci: Results from the gliogene consortium Journal Article
| Authors: | Shete, S.; Lau, C. C.; Houlston, R. S.; Claus, E. B.; Barnholtz-Sloan, J.; Lai, R.; Il'yasova, D.; Schildkraut, J.; Sadetzki, S.; Johansen, C.; Bernstein, J. L.; Olson, S. H.; Jenkins, R. B.; Yang, P.; Vick, N. A.; Wrensch, M.; Davis, F. G.; McCarthy, B. J.; Leung, E. H. C.; Davis, C.; Cheng, R.; Hosking, F. J.; Armstrong, G. N.; Liu, Y.; Yu, R. K.; Henriksson, R.; The Gliogene Consortium; Melin, B. S.; Bondy, M. L. |
| Contributors: | Schubert, E.; DeAngelis, L. |
| Article Title: | Genome-wide high-density SNP linkage search for glioma susceptibility loci: Results from the gliogene consortium |
| Abstract: | 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. ©2011 AACR. |
| Keywords: | adolescent; adult; child; human tissue; aged; middle aged; young adult; major clinical study; single nucleotide polymorphism; polymorphism, single nucleotide; histopathology; cancer risk; united states; glioma; brain neoplasms; cancer susceptibility; family health; genetic predisposition to disease; genetic association; genotype; genome-wide association study; linkage disequilibrium; cancer research; risk assessment; pedigree; genetic susceptibility; human genome; familial cancer; high risk population; genetic risk; dna determination; genome, human; genetic linkage; genetic heterogeneity; chromosome mapping; rare disease; fatality; gene linkage disequilibrium; lod score |
| Journal Title: | Cancer Research |
| Volume: | 71 |
| Issue: | 24 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2011-12-15 |
| Start Page: | 7568 |
| End Page: | 7575 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-11-0013 |
| PROVIDER: | scopus |
| PMCID: | PMC3242820 |
| PUBMED: | 22037877 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 February 2012" - "CODEN: CNREA" - "Source: Scopus" |
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