TY - JOUR
T1 - Fetal and Maternal Candidate Single Nucleotide Polymorphism Associations With Cerebral Palsy: A Case-Control Study
AU - O'Callaghan, Michael
AU - MacLennan, Alastair
AU - Gibson, Catherine
AU - McMichael, Gai
AU - Haan, Eric
AU - Broadbent, Jessica
AU - Goldwater, Paul
AU - Painter, Jodie
AU - Montgomery, Grant
AU - Dekker, G
PY - 2012/2
Y1 - 2012/2
N2 - OBJECTIVE: Previous studies have suggested associations between certain genetic variants and susceptibility to cerebral palsy (CP). This study was designed to assess established and novel maternal and child genetic and epidemiologic risk factors for CP along with their interactions. METHODS: DNA from 587 case and 1154 control mother-child pairs was analyzed. A panel of 35 candidate single nucleotide polymorphisms (SNPs) were examined and included SNPs in genes associated with (1) thrombophilia, (2) inflammation, and (3) risk factors for CP (eg, preterm birth). Comparisons were specified a priori and made by using a χ 2 test. RESULTS: There were 40 fetal and 28 maternal associations with CP when analyzed by CP subtype, gestational age, genotypes of apolipoprotein E, and haplotypes of mannose-binding-lectin. After Bonferroni correction for multiple testing, no fetal or maternal candidate SNP was associated with CP or its subtypes. Only fetal carriage of prothrombin gene mutation remained marginally associated with hemiplegia in term infants born to mothers with a reported infection during pregnancy. Odds ratio directions of fetal SNP associations were compared with previously reported studies and confirmed no trend toward association. CONCLUSIONS: Except for the prothrombin gene mutation, individual maternal and fetal SNPs in our candidate panel were not found to be associated with CP outcome. Past reported SNP associations with CP were not confirmed, possibly reflecting type I error from small numbers and multiple testing in the original reports.
AB - OBJECTIVE: Previous studies have suggested associations between certain genetic variants and susceptibility to cerebral palsy (CP). This study was designed to assess established and novel maternal and child genetic and epidemiologic risk factors for CP along with their interactions. METHODS: DNA from 587 case and 1154 control mother-child pairs was analyzed. A panel of 35 candidate single nucleotide polymorphisms (SNPs) were examined and included SNPs in genes associated with (1) thrombophilia, (2) inflammation, and (3) risk factors for CP (eg, preterm birth). Comparisons were specified a priori and made by using a χ 2 test. RESULTS: There were 40 fetal and 28 maternal associations with CP when analyzed by CP subtype, gestational age, genotypes of apolipoprotein E, and haplotypes of mannose-binding-lectin. After Bonferroni correction for multiple testing, no fetal or maternal candidate SNP was associated with CP or its subtypes. Only fetal carriage of prothrombin gene mutation remained marginally associated with hemiplegia in term infants born to mothers with a reported infection during pregnancy. Odds ratio directions of fetal SNP associations were compared with previously reported studies and confirmed no trend toward association. CONCLUSIONS: Except for the prothrombin gene mutation, individual maternal and fetal SNPs in our candidate panel were not found to be associated with CP outcome. Past reported SNP associations with CP were not confirmed, possibly reflecting type I error from small numbers and multiple testing in the original reports.
KW - Candidate gene
KW - Case-control
KW - Cerebral palsy
KW - SNP association
UR - http://www.scopus.com/inward/record.url?scp=84856513041&partnerID=8YFLogxK
U2 - 10.1542/peds.2011-0739
DO - 10.1542/peds.2011-0739
M3 - Article
SN - 0031-4005
VL - 129
SP - e414-e423
JO - Pediatrics
JF - Pediatrics
IS - 2
ER -