The Meningioma Consortium: Genome-Wide Association Study

Sponsor: Yale University

Location(s): United States


Meningioma is the most common primary brain tumor, present in up to one percent of adults, and although often considered benign, has survival comparable to breast cancer. Information on risk factors is extremely limited. In an effort to better define such factors, we are conducting a comprehensive population-based, case/control study of meningioma that includes 1600 cases and 1600 controls drawn from Massachusetts, Connecticut, North Carolina, California and Texas. This will represent the largest population-based collection of meningioma cases worldwide, with more than double the number of cases of any existing study. We are currently collecting biological specimens, and extensive exposure and phenotypic data with funding from the National Institutes of Health (NIH R01s CA109468, CA109461, CA109745, CA108473, and CA109475). In this application we request funds to genotype the study subjects to find inherited risk loci for meningioma. Our aims are to
1) Conduct the first genome wide association study (GWAS) of meningioma using the 1360 Caucasian cases from our ongoing case/control project and 3420 Caucasian controls drawn from the first half of three control series
2) Using 700 additional Caucasian meningioma subjects drawn from our clinical series and the second half of the above mentioned controls (n=3420), replicate candidates from Aim 1 that yielded p<10-5 for association with meningioma. Variants with p < 5.0*10-8 will be considered significant for genome wide association with meningioma risk from combined stage 1 and stage 2 analyses,
3) Replicate previous associations from the Interphone study8a of meningioma risk with variants in BRIP1 (the breast cancer susceptibility gene (BRCA1)-interacting protein) and ATM (ataxia telangiectasia mutated gene) and
4) Replicate previous associations from the Tineas Capitas study of meningioma risk with variants in DNA repair genes (KRAS2, ERCC2, CCND1).