Cohort-Based GWAS of Glioma
Principal Investigator
Name
Preetha Rajaraman
Degrees
-
Institution
NCI, DCEG, REB
Position Title
-
Email
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
2008-0253
Initial CDAS Request Approval
Apr 27, 2009
Title
Cohort-Based GWAS of Glioma
Summary
We seek permission to perform a genome-wide scan on incident gliomas occuring in the PLCO population. Genome-wide scan studies require large numbers, and we will use the results in combination with other data sets: (1) immediately combine with two other NCI cohorts (Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC) and the Agricultural Health study) and two large case-control studies with high response rates that will be scanned at the same time (March 2009), (2) test the top findings from three scans from case-series and less robust case-control studies, expected soon, and pool data if indicated, and (3) initiate the planned GWAS of 17 cohorts belonging to the NCI Cohort Consortium. PLCO, like other prospective cohorts, is critical for studying glioma. The often fatal nature of glioblastoma, the most common type of glioma, limits the value of case-control studies because of possible survivor bias. In settings where rapid case ascertainment is possible, selection and recruitment of appropriate controls is difficult, introducing other possible selection biases. Thus, when the most significant findings are reported from case-control studies next spring, replication in cohorts will be vital to understanding suceptibility to this highly lethal disease. PLCO also offers a unique opportunity to explore future gene-environment interactions, with the availability of pre-diagnostic information on exposures. Since some PLCO subjects have already been genotyped, we will use those as controls where possible, providing savings in cost and specimens. We will fine map any SNPs that reach significance in a joint analysis of all three data sets combined (expected 1-2 SNPs). Research team: See attached research plan section C4
Aims
1. Primary Specific Aim : To conduct a cohort-based GWAS of glioma. A cohort-based GWAS has the advantage of: a) ascertainment of all cases including rapidly fatal histologies (e.g. GBM). b) availability of pre-diagnostic components and information from questionnaire and serum, for future gene-environment studies. 2. Secondary Specific Aim : 1-2 SNP associations are anticipated to reach genome-wide significance after addition of cohort data in the joint analysis. We will fine map these regions using tag SNPs from HapMap Phase II (including Caucasians, East Asians and Yoruba) to identify surrogate SNPs for each bin across the three populations. The fine-mapping strategy will include testing of other populations included in our study (e.g. African Americans and East Asians) to determine if the signals can be restricted to a smaller region of the genome.
Collaborators
Stephen Chanock (NCI, DCEG)
Joseph Fraumeni (NCI, DCEG)
Patricia Hartge (NCI, DCEG)
Robert Hoover (NCI, DCEG)
Peter Inskip (NCI, DCEG)
Martha Linet (NCI, DCEG)
Preetha Rajaraman (NCI, DCEG)
Sophia Wang (NCI, DCEG)
Related Publications
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Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.
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J. Natl. Cancer Inst. 2015 Dec; Volume 107 (Issue 12): Pages djv279 PUBMED -
Further Confirmation of Germline Glioma Risk Variant rs78378222 in TP53 and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data.
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Personal history of diabetes, genetic susceptibility to diabetes, and risk of brain glioma: a pooled analysis of observational studies.
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Joint effects between five identified risk variants, allergy, and autoimmune conditions on glioma risk.
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Known glioma risk loci are associated with glioma with a family history of brain tumours -- a case-control gene association study.
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Int. J. Cancer. 2013 May 15; Volume 132 (Issue 10): Pages 2464-8 PUBMED -
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Hum. Genet. 2012 Dec; Volume 131 (Issue 12): Pages 1877-88 PUBMED -
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