Sexspecific glioma genomewide association study identifies. To identify susceptibility loci for ba, we performed a genome wide association study on two groups of ba patients. Genomewide association study metaanalysis identifies. The results of genomewide association studies gwas and casecontrol studies performed to investigate the associations between epidermal growth factor receptor egfr gene polymorphisms and glioma risk are controversial. Metaanalysis of multiple genomewide association gwa studies has become common practice over the past few years. Conditional analysis was implemented using gcta software. Beatrice melin, richard houlston, melissa bondy and colleagues report results of a largescale genomewide association study of glioma. We discovered and replicated two novel loci associated with.
Here, we performed a metaanalysis to investigate the association between 6 polymorphisms in the ercc genes rs3212986, rs11615, rs181, rs1799793, rs238406, rs17655 and glioma risk. Manhattan plot of genomewide association study metaanalysis results including the spain cohort. 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. The subjects with cdkn2ab rs4977756 polymorphism might have higher glioma. Association of 3 polymorphisms in ercc2 gene rs181, rs1799793, and rs238406 with glioma risk.
We conducted a new independent gwas of glioma using 1,856 cases and 4,955 controls from 14 cohort studies, 3 casecontrol studies, and 1 populationbased caseonly study and found evidence of. Metaanalysis geneset enrichment of variant associations image credit. The direction and magnitude of the signal were consistent for samples from cohort and casecontrol studies, but the strength of the association was more pronounced for loci rs6010620 20q. Alzheimers disease susceptibility genes in lowgrade glioma. Pdf genomewide association study identifies multiple. Genomewide association study of brain connectivity changes. The tcga data portal contains clinical information, genomic characterization data of the tumor genomes and provides a. Genome wide association studies are one of the initial steps in coming to that understanding.
We investigated the association between 8,831,628 genetic variants and risk of glioma. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for gwas of colorectal cancer 2,906 cases, 3,416 controls that have not. To identify new glioma susceptibility loci, we conducted a. Genomewide association analyses in 128,266 individuals. Genome wide association studies gwas have successfully identified novel susceptibility loci for colorectal cancer. We conducted a new independent gwas of glioma using 1,856 cases and 4,955 controls from 14 cohort studies, 3 casecontrol studies, and 1 populationbased caseonly study and found evidence of strong replication for three of the seven previously reported associations at 20q. To identify new glioma susceptibility loci, we conducted a metaanalysis of four gwas totalling 4,147 cases and 7,435 controls, with imputation using genomes and uk10k project data as reference. In this study, we performed a genome wide association study gwas among chinese populations to identify novel genetic loci contributing to susceptibility to hbvrelated hcc. The main advantage of this technique is the maximization of power to detect. Metaanalysis associations between egfr gene polymorphisms. Hepatocellular carcinoma hcc is one of the most common cancers worldwide. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. We advance the understanding of human health and biology through novel computational methods applied to large and diverse datasets.
We conducted a new genome wide association scan of glioma gliomascan to validate previously reported risk regions and to attempt to identify additional novel risk loci. To identify risk variants for glioma, we conducted a principal componentadjusted genome wide association study. There was no significant association observed in the overall. The tests implemented include 1 binary casecontrol phenotypes, single and multiple quantitative phenotypes, 2 bayesian and frequentist tests, 3 ability to condition upon an arbitrary set of covariates and or snps and 4 various different methods for the dealing with imputed snps. Association between common polymorphisms in ercc gene and gl. Glutathione stransferase genes variants and glioma risk. Largest ever brain cancer study reveals new secrets to. Association between common polymorphisms in ercc gene and. Genotypebased gene signature of glioma risk neurooncology. Mar 15, 2018 we performed an analysis of genetic variants associated with atopy to assess the relationship with glioma risk using mendelian randomisation mr, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.
Original article cdkn2ab rs4977756 and glioma risk. This study with 12814 glioma patients and 21140 controls revealed a significant result. Potential sexspecific genetic effects were assessed in autosomal snps and sex chromosome variants for. The genomewide association study gwas for the gs cohort yielded two significant. Previous glioma genome wide association studies gwas have not stratified by sex. Ethnicity is an important factor associated with gst gene variants and glioma risk. In this study, meta analyses were performed for two groups of diseases, cancerous diseases, e.
To identify risk variants for glioma, we conducted a metaanalysis of two genomewide association studies by genotyping 550k tagging snps in a total of 1,878 cases and 3,670 controls, with. Previous genomewide association studies gwass have shown that common genetic variation contributes to the heritable risk of glioma. Genetic predisposition to glioma is well known in the settings of rare familial tumor syndromes. To identify genetic associations with human lifespan, several genomewide association gwa studies have been performed 7,8,9,10,11,12,14,15,16,17,18,19,20. The pubmed, embase, and web of science were searched up to september 6, 2016, for studies on the association between ercc polymorphisms and glioma. Summary measures odds ratios and 95% confidence intervals were obtained from each study, and a metaanalysis was performed using an inverse variance fixed effect model. Genomewide association studies, for better or for worse, have ushered in the exciting era of personalized medicine and personal genetic testing.
We identified genetic instruments for 37 potentially modifiable risk factors and evaluated their association with glioma risk using data from a genomewide association study of 12,488. With the advances in sequencing technologies and genomewide association studies gwas, several inherited variants that increase glioma risk have been identified. After targeted sequencing and functional annotation. Quality control and conduct of genomewide association. Joint analysis of three genomewide association studies of. Association between dna repair gene polymorphisms and risk. The majority of these gwas susceptibility variants reside in noncoding regions and the causal genes underlying the associations are largely unknown. Mar 27, 2017 the researchers carried out two new genomewide studies and combined the results with six previous studies in a metaanalysis involving in total 12,496 cases of glioma and 18,190 people without.
The association of 6 variants of 8q24 and the risk of glioma. Glioma accounts for 80% of malignant brain tumors, but its etiologic determinants remain elusive. Genomewide association studies gwas have revolutionized human genetics. Savage sa, bertazzi pa, tucker ma, chanock s, caporaso ne 2009 a genomewide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Study of glioma susceptibility in dogs may yield insights for humans. This metaanalysis of the association between germline snps in dna repair genes and the risk of glioma suggests that dna repair genes ercc1, ercc2 xpd, and xrcc1 are lowpenetrance glioma risk genes, while mgmt and parp1 polymorphisms have protective effects on glioma development. Feb 02, 2018 gioma makes up 80% of all malignant brain tumors in adults. Choi sh, ruggiero d, sorice r, song c, nutile t, vernon smith a, et al. Cdh18 was reported in a metaanalysis of depression. Metaanalysis findings of association between rs181 polymorphism and glioma are summarized in table table4.
Genomewide association study identifies three candidate genes linked to glioma development. Genomewide association study identifies possible genetic. Metaanalysis of genomewide association studies provides. Six novel loci associated with circulating vegf levels. A total of 10 studies involving 3289 cases and 4718 controls were included. This tutorial is a learning resource that outlines the basic process and provides specific software tools for implementing a complete genome. A genome wide association study gwas of 280 cases identified the hepatic cholesterol transporter abcg8 as a locus associated with risk for gallstone disease, but findings have not been reported from any other gwas of this phenotype. Metasoft is a free, opensource metaanalysis software tool for genomewide association study analysis, designed to perform a range of basic and advanced metaanalytic methods in an efficient. A program for the analysis of single snp association in genome wide studies. However, none of these associations reached statistical significance at the genomewide association level supplementary table 2. We performed a genomewide association study of sleep duration and morningness in 128,266 individuals from the uk biobank study.
Genome wide association study subject areas on research. To maximize sample size, we metaanalyzed data on 807,553 individuals 246,363 cases and 561,190 controls from the three largest genomewide association studies of depression. Genomewide association studies gwas have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma gbm or nongbm tumors. Here, we describe a multiethnic genome wide association study including 21 079 middleaged to elderly participants from 29 populationbased cohorts, who were free of dementia and stroke. Ten studies including 8818 cases and 17,551 controls were collected to conduct a metaanalysis to evaluate the associations between 6 variants in 8q24 and glioma risk. Through the linkage studies, genetic association studies and genomewide association studies gwas, people have identi. These risk loci for glioma include glioma susceptibility loci such as xrcc1 w399r and arg194trp, parp1 a762v, mgmt f84l, ercc1 a8092c, ercc2 q751k, il. 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. While apoe is ranked the number one alzheimers disease ad susceptibility gene, many other susceptibility genes have been identified in genome wide association studies. They have led to the identification of thousands of loci that affect both normal variation and susceptibility to disease, and. Genomewide association study identifies five susceptibility. Jan 29, 2020 genomewide association study of brain connectivity changes for alzheimers disease. To understand the genetic control of flavor, we report the metaanalysis of genomewide association studies gwas using 775 tomato accessions and 2,316,117 snps from three gwas panels. Read genomewide association study of glioma and metaanalysis, human genetics on deepdyve, the largest online rental service for scholarly research with thousands of academic.
Three genome wide association studies gwas have examined escc and two subsequent analyses used combinations of the three studies 4, 5 to report as many as 12 loci associated with escc risk. In genomewide analysis, an association with risk was suggested for 129 genetic variants p metaanalysis of multiple genomewide association gwa studies has become common practice over the last few years. Genomewide association study identifies a new locus at 7q21. Recent genomewide association studies gwas have identified seven new susceptibility regions. In the metaanalysis in this study, a significant association was found between gstp1 ile105val valval vs. Plot of the log10 p values of association between the 7,110,321 markers after meta. To date, five gwas reports have been published and have led to the discovery of about 14 snps in 7 chromosome regions associated with glioma risk for individuals of european descent 37. Author summary the etiology of biliary atresia ba is unknown and likely complex. Four additional loci have been reported based on an interaction with alcohol consumption, a known risk factor for escc 4. Genomewide association study of glioma subtypes identifies. Studies included in the gliomascan genomewide association study gwas and replication metaanalysis results studyspecific population characteristics are summarized in table 1. Known glioma risk loci are associated with glioma with a.
Metaanalysis of new genomewide association studies of. Anderson cancer center conducted a metaanalysis of two genomewide association studies gwas by genotyping 550 k tagging single nucleotide polymorphisms tsnps in a total of 1,878 cases and 3,670 controls, with validation in three additional independent series totaling 2,545 cases and 2,953. Environmental, infectious, and genetic risk factors have all been proposed, and the leading hypothesis in the field is that a combination of these factors is responsible for disease manifestation. Chanock sj, chatterjee n 2010 estimation of effect size distribution from genomewide. Development of risk prediction models for glioma based on. The following chapter provides an overview of the current state of research in the epidemiology of intracranial glioma. Association between dna repair gene polymorphisms and risk of. Genomewide association study of glioma and metaanalysis. Tcps was a colonoscopybased casecontrol study conducted in nashville, tennessee from 2003 to 2010. A metaanalysis of genomewide association studies of. Genomewide association study identifies multiple susceptibility loci for glioma article pdf available in nature communications 6. Study of glioma susceptibility in dogs may yield insights.
Details of the 19 studies participating in gliomascan are provided in table 1. Genome wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and nonglioblastoma tumors. Metaanalysis of genomewide association studies and. Genomewide metaanalysis of depression identifies 102. Metaanalysis findings of association between rs181 polymorphism and glioma are summarized in table 4. Despite genetic susceptibility loci identified by genome wide association study gwas, the agnostic approach leaves open the possibility that other susceptibility genes remain to be discovered. This study aimed to analyze the expression of apoe and the next 23 ranked ad susceptibility genes in malignant gliomas to identify significantly cooccurrent genes. More and more studies suggest that the number of genetic variants plays a signi.
Furthermore, some diseases have a positive association with the c and some with the a allele. Recent genomic analyses, using the genomewide association study gwas design, have identified several inherited risk variants that are associated with increased glioma risk. We lead and collaborate in national and international research, advise at the highest levels of government and academia, and actively seek collaborations, recognizing the value and impact of team science. Frontiers telomerase reverse transcriptase polymorphism. In genetics, a genomewide association study gwa study, or gwas, also known as whole genome association study wga study, or wgas, is an observational study of a genomewide set of genetic. A metaanalysis of genomewide association studies of epigenetic age acceleration. Lauren solomon, broad communications, broad institute, cambridge, ma.
Previous genome wide association studies gwass have shown that common genetic variation contributes to the heritable risk of glioma. To date, no studies have performed genomewide analyses to find novel genetic variants associated with glioma risk in children and aya. To identify risk variants for glioma, we conducted a metaanalysis of two genomewide association studies by genotyping 550k tagging snps in a total of 1,878 cases and 3,670 controls, with validation in three additional independent series totaling 2,545 cases and 2,953 controls. Here we performed a transcriptomewide association study. The main advantage of this technique is the maximization of power to detect the subtle genetic effects for common traits. We conducted a new independent gwas of glioma using 1,856 cases and 4,955 controls from 14 cohort studies, 3 casecontrol studies, and 1 populationbased caseonly study. A genomewide association study identifies a susceptibility. Twosample mr was undertaken using genome wide association study data. A number of genetic regions have been identified in genomewide association studies gwas. Incidence of glioma is approximately 50% higher in males. Jul 15, 2011 colorectal cancer is the second leading cause of cancer death in developed countries.
Eligible participants, between 45 and 70 years of age, were identified from patients scheduled for colonoscopy at the vanderbilt gastroenterology clinic and the veterans affairs tennessee valley health system nashville campus. In china, chronic hepatitis b virus hbv infection remains the major risk factor for hcc. Transcriptomewide association study identifies new. Therefore, a metaanalysis was performed to specifically investigate the association with gstp1 ile105val and ala114val, gstt1 nullpresent and gstm1 nullpresent variants and the risk of glioma that included data from this casecontrol study of 724 patients combined with other recently published and relevant studies.
The power of metaanalysis in genomewide association studies. This metaanalysis of the association between germline snps in dna repair genes and the risk of glioma suggests that dna repair genes ercc1, ercc2 xpd, and xrcc1 are lowpenetrance glioma risk genes, while mgmt and parp1 polymorphisms have protective effects on glioma. They identify five new risk loci for glioblastoma and. A metaanalysis of an association between the xrcc1. The gwama genomewide association metaanalysis software has been developed to perform metaanalysis of summary statistics generated from genomewide association studies of dichotomous phenotypes or quantitative traits. Ten studies including 8818 cases and 17,551 controls were collected to conduct a metaanalysis to evaluate the associations between 6 variants in 8q24 and glioma. Rtel1 tagging snps and haplotypes were associated with glioma. Metasoft is a metaanalysis software designed for performing a range of basic and advanced metaanalytic methods.