Title | Genome-wide high-density SNP linkage search for glioma susceptibility loci: results from the Gliogene Consortium. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Shete, S, Lau, CC, Houlston, RS, Claus, EB, Barnholtz-Sloan, J, Lai, R, Il'yasova, D, Schildkraut, J, Sadetzki, S, Johansen, C, Bernstein, JL, Olson, SH, Jenkins, RB, Yang, P, Vick, NA, Wrensch, M, Davis, FG, McCarthy, BJ, Leung, EHon-chiu, Davis, C, Cheng, R, Hosking, FJ, Armstrong, GN, Liu, Y, Yu, RK, Henriksson, R, Melin, BS, Bondy, ML |
Corporate Authors | Gliogene Consortium |
Journal | Cancer Res |
Volume | 71 |
Issue | 24 |
Pagination | 7568-75 |
Date Published | 2011 Dec 15 |
ISSN | 1538-7445 |
Keywords | Adolescent, Adult, Aged, Brain Neoplasms, Child, Chromosome Mapping, Family Health, Female, Genetic Heterogeneity, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Genotype, Glioma, Humans, Linkage Disequilibrium, Lod Score, Male, Middle Aged, Pedigree, Polymorphism, Single Nucleotide, United States, Young Adult |
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. |
DOI | 10.1158/0008-5472.CAN-11-0013 |
Alternate Journal | Cancer Res |
PubMed ID | 22037877 |
PubMed Central ID | PMC3242820 |
Grant List | R01 CA052689-17 / CA / NCI NIH HHS / United States R01CA126831 / CA / NCI NIH HHS / United States 5R01 CA119215 / CA / NCI NIH HHS / United States 5P30CA16672 / CA / NCI NIH HHS / United States 5R01 CA070917 / CA / NCI NIH HHS / United States R01 CA070917 / CA / NCI NIH HHS / United States R01 CA070917-09 / CA / NCI NIH HHS / United States P50097257 / / PHS HHS / United States R01 CA052689 / CA / NCI NIH HHS / United States R01 CA126831 / CA / NCI NIH HHS / United States R01 CA119215-05 / CA / NCI NIH HHS / United States R01 CA126831-05 / CA / NCI NIH HHS / United States R01 CA119215 / CA / NCI NIH HHS / United States R01CA52689 / CA / NCI NIH HHS / United States |
Genome-wide high-density SNP linkage search for glioma susceptibility loci: results from the Gliogene Consortium.
Similar Publications
DNA Methylation-Derived Immune Cell Proportions and Cancer Risk in Black Participants. Cancer Res Commun. 2024;4(10):2714-2723. | .
StratoMod: predicting sequencing and variant calling errors with interpretable machine learning. Commun Biol. 2024;7(1):1316. | .
Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk. BMC Med Genomics. 2024;17(1):255. | .