title: Addition of host genetic variants in a prediction rule for post meningitis hearing loss in childhood: a model updating study.
abstract: BACKGROUND
  Sensorineural hearing loss is the most common sequela in survivors of bacterial meningitis (BM). In the past we developed a validated prediction model to identify children at risk for post-meningitis hearing loss. It is known that host genetic variations, besides clinical factors, contribute to severity and outcome of BM. In this study it was determined whether host genetic risk factors improve the predictive abilities of an existing model regarding hearing loss after childhood BM.
  
  
  METHODS
  Four hundred and seventy-one Dutch Caucasian childhood BM were genotyped for 11 single nucleotide polymorphisms (SNPs) in seven different genes involved in pathogen recognition. Genetic data were added to the original clinical prediction model and performance of new models was compared to the original model by likelihood ratio tests and the area under the curve (AUC) of the receiver operating characteristic curves.
  
  
  RESULTS
  Addition of TLR9-1237 SNPs and the combination of TLR2 + 2477 and TLR4 + 896 SNPs improved the clinical prediction model, but not significantly (increase of AUC's from 0.856 to 0.861 and from 0.856 to 0.875 (p = 0.570 and 0.335, respectively). Other SNPs analysed were not linked to hearing loss.
  
  
  CONCLUSIONS
  Although addition of genetic risk factors did not significantly improve the clinical prediction model for post-meningitis hearing loss, AUC's of the pre-existing model remain high after addition of genetic factors. Future studies should evaluate whether more combinations of SNPs in larger cohorts has an additional value to the existing prediction model for post meningitis hearing loss.
authors.affiliation: Department of Pediatric Infectious Diseases - Immunology, and Rheumatology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marieke S
authors.initials: MS
authors.lastname: Sanders
authors.forename: Rogier C J
authors.initials: RC
authors.lastname: de Jonge
authors.forename: Caroline B
authors.initials: CB
authors.lastname: Terwee
authors.forename: Martijn W
authors.initials: MW
authors.lastname: Heymans
authors.forename: Irene
authors.initials: I
authors.lastname: Koomen
authors.forename: Sander
authors.initials: S
authors.lastname: Ouburg
authors.forename: Lodewijk
authors.initials: L
authors.lastname: Spanjaard
authors.forename: Servaas A
authors.initials: SA
authors.lastname: Morré
authors.forename: A Marceline
authors.initials: AM
authors.lastname: van Furth
mesh_terms: D019540:Area Under Curve; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000382:microbiology*; D006801:Humans; D007223:Infant; D008297:Male; D016920:Meningitis, Bacterial / Q000150:complications* / Q000235:genetics*; D015233:Models, Statistical; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors