title: Genetic and clinical contributions to cerebral palsy: a multi-variable analysis.
abstract: OBJECTIVE
  This study aims to examine single nucleotide polymorphism (SNP) associations with cerebral palsy in a multi-variable analysis adjusting for potential clinical confounders and to assess SNP-SNP and SNP-maternal infection interactions as contributors to cerebral palsy.
  
  
  METHODS
  A case control study including 587 children with cerebral palsy and 1154 control children without cerebral palsy. Thirty-nine candidate SNPs were genotyped in both mother and child. Data linkage to perinatal notes and cerebral palsy registers was performed with a supplementary maternal pregnancy questionnaire. History of known maternal infection during pregnancy was extracted from perinatal databases.
  
  
  RESULTS
  Both maternal and fetal carriage of inducible nitric oxide synthase SNP rs1137933 were significantly negatively associated with cerebral palsy in infants born at less than 32 weeks gestation after adjustment for potential clinical confounders and correction for multiple testing (odds ratio 0.55, 95% confidence interval 0.38-0.79; odds ratio 0.57, 95% confidence interval 0.4-0.82, respectively). Analysis did not show any statistically significant SNP-SNP or SNP-maternal infection interactions after correction for multiple testing.
  
  
  CONCLUSIONS
  Maternal and child inducible nitric oxide synthase SNPs are associated with reduced risk of cerebral palsy in infants born very preterm. There was no evidence for statistically significant SNP-SNP or SNP-maternal infection interactions as modulators of cerebral palsy risk.
authors.affiliation: Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, Robinson Institute, Adelaide, SA 5006, Australia. michael.ocallaghan@adelaide.edu.au
authors.forename: Michael E
authors.initials: ME
authors.lastname: O'Callaghan
authors.forename: Alastair H
authors.initials: AH
authors.lastname: Maclennan
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Gibson
authors.forename: Gai L
authors.initials: GL
authors.lastname: McMichael
authors.forename: Eric A
authors.initials: EA
authors.lastname: Haan
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Broadbent
authors.forename: Peter A
authors.initials: PA
authors.lastname: Baghurst
authors.forename: Paul N
authors.initials: PN
authors.lastname: Goldwater
authors.forename: Gustaaf A
authors.initials: GA
authors.lastname: Dekker
mesh_terms: D002547:Cerebral Palsy / Q000235:genetics*; D015986:Confounding Factors, Epidemiologic; D016207:Cytokines / Q000235:genetics; D005260:Female; D060005:Genotyping Techniques; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D009035:Mothers; D015999:Multivariate Analysis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019851:Thrombophilia / Q000235:genetics
chemical_list: D016207:Cytokines; D037601:Mannose-Binding Lectin; D052247:Nitric Oxide Synthase Type II; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: SNP; case control; cerebral palsy; infection; interaction; pregnancy