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Glioma risk associated with extent of estimated European genetic ancestry in African Americans and Hispanics.

ABSTRACT: Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case-Control Study and GliomaSE Case-Control Study previously estimated to have <80% EA, or self-identify as non-White. We estimated global and local ancestry using fastStructure and RFMix, respectively, using 1,000 genomes project reference populations. Within groups with ?40% AA (AFR_?0.4 ), and??15% NAA (AMR_?0.15 ), genome-wide association between local EA and glioma was evaluated using logistic regression conditioned on global EA for all gliomas. We identified two regions (7q21.11, p?=?6.36?×?10^-4 ; 11p11.12, p?=?7.0?×?10^-4 ) associated with increased EA, and one associated with decreased EA (20p12.13, p?=?0.0026) in AFR_?0.4 . In addition, we identified a peak at rs1620291 (p?=?4.36?×?10^-6 ) in 7q21.3. Among AMR_?0.15 , we found an association between increased EA in one region (12q24.21, p?=?8.38?×?10^-4 ), and decreased EA in two regions (8q24.21, p?=?0. 0010; 20q13.33, p?=?6.36?×?10^-4 ). No other significant associations were identified. This analysis identified an association between glioma and two regions previously identified in EA populations (8q24.21, 20q13.33) and four novel regions (7q21.11, 11p11.12, 12q24.21 and 20p12.13). The identifications of novel association with EA suggest regions to target for future genetic association studies.

SUBMITTER: Ostrom QT

PROVIDER: S-EPMC6785354 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Glioma risk associated with extent of estimated European genetic ancestry in African Americans and Hispanics.

Ostrom Quinn T QT Egan Kathleen M KM Nabors L Burt LB Gerke Travis T Thompson Reid C RC Olson Jeffrey J JJ LaRocca Renato R Chowdhary Sajeel S Eckel-Passow Jeanette E JE Armstrong Georgina G Wiencke John K JK Bernstein Jonine L JL Claus Elizabeth B EB Il'yasova Dora D Johansen Christoffer C Lachance Daniel H DH Lai Rose K RK Merrell Ryan T RT Olson Sara H SH Sadetzki Siegal S Schildkraut Joellen M JM Shete Sanjay S Houlston Richard S RS Jenkins Robert B RB Wrensch Margaret R MR Melin Beatrice B Amos Christopher I CI Huse Jason T JT Barnholtz-Sloan Jill S JS Bondy Melissa L ML

International journal of cancer 20190422 3

Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained ...[more]

PMID: 30963577

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Project description:BackgroundFamily history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.MethodsIndividual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.ResultsMean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered "no" to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.ConclusionsMean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP.

Dataset Information

Glioma risk associated with extent of estimated European genetic ancestry in African Americans and Hispanics.

Publications

Glioma risk associated with extent of estimated European genetic ancestry in African Americans and Hispanics.

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