Dataset Information

Cohort-Based Genome-Wide Association Study of Glioma (GliomaScan)

ABSTRACT:

We conducted a new independent GWAS of adult glioma using 1,856 cases and 4,955 controls from 14 cohort studies belonging to the Cohort Consortium, 3 case-control studies, and 1 population-based case only study. Cases were newly diagnosed glioma [ICDO-3 codes 9380-9480 or equivalent], and controls were cancer-free at the time of glioma diagnosis. We found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to higher grade tumors being captured in the cohort studies. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.

PROVIDER: phs000652.v1.p1 | EGA |

REPOSITORIES: EGA

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Publications

Genome-wide association study of glioma and meta-analysis.

Rajaraman Preetha P Melin Beatrice S BS Wang Zhaoming Z McKean-Cowdin Roberta R Michaud Dominique S DS Wang Sophia S SS Bondy Melissa M Houlston Richard R Jenkins Robert B RB Wrensch Margaret M Yeager Meredith M Ahlbom Anders A Albanes Demetrius D Andersson Ulrika U Freeman Laura E Beane LE Buring Julie E JE Butler Mary Ann MA Braganza Melissa M Carreon Tania T Feychting Maria M Fleming Sarah J SJ Gapstur Susan M SM Gaziano J Michael JM Giles Graham G GG Hallmans Goran G Henriksson Roger R Hoffman-Bolton Judith J Inskip Peter D PD Johansen Christoffer C Kitahara Cari M CM Lathrop Mark M Liu Chenwei C Le Marchand Loic L Linet Martha S MS Lonn Stefan S Peters Ulrike U Purdue Mark P MP Rothman Nathaniel N Ruder Avima M AM Sanson Marc M Sesso Howard D HD Severi Gianluca G Shu Xiao-Ou XO Simon Matthias M Stampfer Meir M Stevens Victoria L VL Visvanathan Kala K White Emily E Wolk Alicja A Zeleniuch-Jacquotte Anne A Zheng Wei W Decker Paul P Enciso-Mora Victor V Fridley Brooke B Gao Yu-Tang YT Kosel Matthew M Lachance Daniel H DH Lau Ching C Rice Terri T Swerdlow Anthony A Wiemels Joseph L JL Wiencke John K JK Shete Sanjay S Xiang Yong-Bing YB Xiao Yuanyuan Y Hoover Robert N RN Fraumeni Joseph F JF Chatterjee Nilanjan N Hartge Patricia P Chanock Stephen J SJ

Human genetics 20120811 12

Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, ...[more]

PMID: 22886559

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Project description:In this study 3 pooling experiments were performed. In each of the 3 cohorts, a 'case' and a 'control' blood pool was compared - the goal being to identify single nucleotide polymorphisms with significantly different estimated pooling allele frequencies between cases and controls. For cohort 1, 100 individuals with blue eye color were placed in one pool (the 'control' pool) and 100 individuals with brown eye color were placed in another pool ( the 'case' pool). In cohort 2, 131 individuals with age-related macular degeneration were placed in one pool, with 216 control individuals in another pool. In cohort 3, 100 individuals with pseudoexfoliation syndrome were placed in a case pool - in this case the cohort 2 control sample was used as 'controls'. The blue/brown pools were hybridized to Illumina HumanHap550 arrays. The cohort 2 and 3 pools were hybridized to Illumina 1M arrays. After processing, the raw data are summarized to give pooling allele frequency estimates for each pool. The abstract from the paper describing these data is as follows: Genome-wide association studies (GWAS) have now successfully identified important genetic variants associated with many human traits and diseases. The high cost of genotyping arrays in large datasets remains the major barrier to wider utilization of GWAS. We have developed a novel method in which whole blood from cases and controls respectively is pooled prior to DNA extraction for genotyping. We demonstrate proof of principle by clearly identifying the associated variants for eye color, age-related macular degeneration and pseudoexfoliation syndrome in cohorts not previously studied. Blood pooling has the potential to reduce GWAS cost by several orders of magnitude and dramatically shorten gene discovery time. This method has profound implications for translation of modern genetic approaches to a multitude of diseases and traits yet to be analysed by GWAS, and will enable developing nations to participate in GWAS.

Project description:Trachoma is a poorly understood immuno-fibrogenic disease process, initiated by Chlamydia trachomatis (Ct). Differences in conjunctival gene expression profiles between Ethiopians with trachomatous trichiasis (with (TTI) and without (TT) inflammation) and controls (NC) were investigated to identify relevant host responses. Tarsal conjunctival swab samples were collected for RNA isolation and Ct PCR. Transcriptome-wide microarray experiments were conducted on 42 samples (TTI 13, TT 15, NC14). Specific results were confirmed using multiplex quantitative RT-PCR for 16 mRNA targets in an independent collection of case-control samples: 386 case-control pairs (TTI 244, TT 142, NC 386). The gene expression profiles of cases were consistent with: squamous metaplasia (Keratins, SPRR), pro-inflammatory cytokine production (IL-1β, CXCL5, S100A7) and tissue remodelling (MMP7, MMP9, MMP12, HAS3). There was no difference in the level of IFNG between cases and controls. However, cases had increased INDO, NOS2A, and IL13RA2 and reduced IL13. Ct was detected in 1/772. Cases show evidence of ongoing inflammation and tissue remodelling, which were more marked where clinical inflammation was also present. Significantly, these processes appear to be active in the absence of current Ct infection. There was limited evidence of a TH1 response (INDO, NOS2A) and no association between a TH2 response and cases. The epithelium appears actively involved in late cicatricial stages of trachoma through production of pro-inflammatory factors (IL-1β, CXCL5, S100A7). Longitudinal studies are needed to investigate which aetiological factors and pathways are associated with progressive scarring and whether simply controlling chlamydial infection will halt progression in people with established cicatricial disease. Case - control study. Conjunctival swab samples were collected from people with trachomatous trichiasis with (TTI) and without (TT) clinically visable inflammation compared to normal controls (C). Total RNA extracted and analysed on the Illumina WG-6 platrom. Additional extensive qRT-PCR work done on a large set of case-control pairs.

Dataset Information

Cohort-Based Genome-Wide Association Study of Glioma (GliomaScan)

Publications

Genome-wide association study of glioma and meta-analysis.

Similar Datasets

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