title: Leveraging ethnic group incidence variation to investigate genetic susceptibility to glioma: a novel candidate SNP approach.
abstract: OBJECTIVE
  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 or conducting meta-analysis. 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.
authors.affiliation: Yale School of Public Health, Yale School of Medicine New Haven, CT, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Jacobs
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Walsh
authors.forename: Margaret
authors.initials: M
authors.lastname: Wrensch
authors.forename: John
authors.initials: J
authors.lastname: Wiencke
authors.forename: Robert
authors.initials: R
authors.lastname: Jenkins
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.forename: Melissa
authors.initials: M
authors.lastname: Bondy
authors.forename: Matthias
authors.initials: M
authors.lastname: Simon
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Gousias
authors.forename: Johannes
authors.initials: J
authors.lastname: Schramm
authors.forename: Marianne
authors.initials: M
authors.lastname: Labussière
authors.forename: Anna Luisa
authors.initials: AL
authors.lastname: Di Stefano
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Martina
authors.initials: M
authors.lastname: Müller-Nurasyid
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Susanne
authors.initials: S
authors.lastname: Moebus
authors.forename: Lewin
authors.initials: L
authors.lastname: Eisele
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Dewan
authors.forename: Robert
authors.initials: R
authors.lastname: Dubrow
keywords: admixture; ancestry informative markers; brain cancer; candidate SNP association study; ethnicity; glioma; race