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

Adel Fahmideh, Maral; Lavebratt, Catharina; Tettamanti, Giorgio; Schüz, Joachim; Röösli, Martin; Kjaerheim, Kristina; Grotzer, Michael A; Johansen, Christoffer; Kuehni, Claudia E; Lannering, Birgitta; Schmidt, Lisbeth S; Darabi, Hatef; Feychting, Maria (2019). A Weighted Genetic Risk Score of Adult Glioma Susceptibility Loci Associated with Pediatric Brain Tumor Risk. Scientific Reports, 9(1), p. 18142. Nature Publishing Group 10.1038/s41598-019-54701-1

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine

UniBE Contributor:

Kühni, Claudia

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Funders:

[4] Swiss National Science Foundation

Language:

English

Submitter:

Andrea Flükiger-Flückiger

Date Deposited:

10 Dec 2019 12:25

Last Modified:

12 Dec 2019 15:20

Publisher DOI:

10.1038/s41598-019-54701-1

PubMed ID:

31792337

BORIS DOI:

10.7892/boris.136386

URI:

https://boris.unibe.ch/id/eprint/136386

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