A Weighted Genetic Risk Score of Adult Glioma Susceptibility Loci Associated with Pediatric Brain Tumor Risk

Abstract

Genetic risk score (GRS) is used to demonstrate the genetic variants contributing to the polygenic architecture of complex diseases. By using a GRS, we have investigated the additive impact of the known adult glioma susceptibility loci on the pediatric brain tumor (PBT) risk and assessed the proportion of PBT heritability attributable to these susceptibility loci. A GRS was generated for PBTs based on the alleles and associated effect sizes derived from a previously published genome-wide association study on adult glioma. The GRS was calculated in CEFALO, a population-based case-control study of brain tumors in children and adolescents including saliva DNA of 245 cases and 489 controls. The unconditional logistic regression model was used to investigate the association between standardized GRS and risk of PBTs. To measure the variance explained by the effect of GRS, Nagelkerke pseudo-R2 was calculated. The GRS for adult brain tumors was associated with an increased risk of PBTs (OR 1.25 [95% CI 1.06–1.49], p = 0.009) and 0.3% of the variance in PBTs could be explained by the effect of GRS on the liability scale. This study provides evidence that heritable risks of PBTs are in-part attributable to some common genetic variants associated with adult glioma.

Pediatric Brain Tumors: Descriptive Epidemiology, Risk Factors, and Future Directions

“…These variants are predominantly located in TERT (5p15.33), RTEL1 (20q13.33), CCDC26 (8q24.21), and CDKN2BAS (9p21.3; refs. [28][29][30]. A recent study was performed in a U.S. population to assess whether genomewide ancestry differences are associated with risk of ependymoma.…”

Polygenic risk score for atopic dermatitis in the Canadian population

“…E12 In comparison, AUCs derived from PRSs in the literature range from 53% to 76%, 6 and show relatively low percentages of explained variance (0.3% for brain tumor compared with 36% in this study). 7 The PRS based on the Canadian cohorts also carried good predictive values for other allergic phenotypes (for clinical definitions, see this article's Online Repository at www.jacionline.org), with AUCs of 75% for food allergies, 71% for asthma, and 69% for allergic rhinitis (Fig 2, A and B). Interestingly, the discriminative value for asthma was similar than that reported using the Predicting Asthma Risk in Children clinical tool, based on respiratory symptoms occurring before school age (AUC 5 77%), even though the predictive tool proposed in this study is designed to identify children at high risk of developing MSAD and not directly to detect those at high risk of developing asthma.…”

Heritability of nervous system tumors: a sibling-based design

“…In conclusion, the variation in susceptibility to nervous system tumors was predominantly attributable to non-shared environmental factors (71%), followed by inherited genetic factors (29%). Although the effect of inherited genes on the total risk of developing nervous system tumors is more pronounced among children, adults and children may share some common inherited genetic factors ( 23 ). The genetic architecture of nervous system tumors and the environmental exposures involved in the development of these tumors are to be explored.…”