Leveraging ethnic group incidence variation to investigate genetic susceptibility to glioma: A novel candidate SNP approach

Frontiers in Genetics

Melissa eBondy¹  Marianne eLabussiere²  Marc eSanson²  Anna Luisa eDi Stefano²  Andre eFranke³  H-Erich eWichmann⁴  Martina eMüller-Nurasyid⁴  Richard eHoulston⁵  Robert eJenkins⁶  Stefan eSchreiber⁷  Susanne eMoebus⁸  Lewin eEisele⁸  John eWiencke⁹  Kyle M. Walsh⁹  Margaret eWrensch⁹  Konstantinos eGousias^1,10  Matthias eSimon^1,10  Johannes eSchramm^1,10  Andrew eDeWan^1,11  Daniel Ian Jacobs^1,11  Robert eDubrow^1,11 

[1] Baylor College of Medicine;Centre de Recherche de l’Institut du Cerveau et de la Moëlle épinière (CRICM);Christian-Albrechts-University Kiel;Helmholtz Zentrum München—German Research Center for Environmental Health;Institute of Cancer Research;Mayo Clinic College of Medicine;University Clinic Schleswig-Holstein;University Hospital of Essen;University of California San Francisco;Universitätskliniken Bonn;Yale School of Public Health;

关键词: Glioma;    race;    admixture;    Ancestry informative markers;    ethnicity;    candidate SNP association study;   

DOI  :  10.3389/fgene.2012.00203

来源: DOAJ

【 摘 要 】

Objectives:Using a novel candidate SNP approach, we aimed to identify a possible genetic basis for the higher glioma incidence in Whites relative to East Asians and African-Americans. Methods: We hypothesized that genetic regions containing SNPs with extreme differences in allele frequencies across ethnicities are most likely to harbor susceptibility variants. We used International HapMap Project data to identify 3,961 candidate SNPs with the largest allele frequency differences in Whites compared to East Asians and Africans and tested these SNPs for association with glioma risk in a set of White cases and controls.Top SNPs identified in the discovery dataset were tested for association with glioma in five independent replication datasets.Results:No SNP achieved statistical significance in either the discovery or replication datasets after accounting for multiple testing.However, the most strongly associated SNP, rs879471, was found to be in linkage disequilibrium with a previously identified risk SNP, rs6010620, in RTEL1.We estimate rs6010620 to account for a glioma incidence rate ratio of 1.34 for Whites relative to East Asians.Conclusions:We explored genetic susceptibility to glioma using a novel candidate SNP method which may be applicable to other diseases with appropriate epidemiologic patterns.

【 授权许可】

Unknown