Evaluation of 64 candidate single nucleotide polymorphisms as risk factors for neural tube defects in a large Irish study population.
Citation:
Carter TC, Pangilinan F, Troendle JF, Molloy AM, VanderMeer J, Mitchell A, Kirke PN, Conley MR, Shane B, Scott JM, Brody LC, Mills JL, Evaluation of 64 candidate single nucleotide polymorphisms as risk factors for neural tube defects in a large Irish study population., American journal of medical genetics. Part A, 155A, 1, 2011, 14-21Download Item:
Abstract:
Abstract
Individual studies of the genetics of neural tube defects (NTDs) contain results on a small number
of genes in each report. To identify genetic risk factors for NTDs, we evaluated potentially
functional single nucleotide polymorphisms (SNPs) that are biologically plausible risk factors for
NTDs but that have never been investigated for an association with NTDs, examined SNPs that
previously showed no association with NTDs in published studies, and tried to confirm previously
reported associations in folate-related and non-folate-related genes. We investigated 64 SNPs in
34 genes for association with spina bifida in up to 558 case-families (520 cases, 507 mothers, 457
fathers) and 994 controls in Ireland. Case-control and mother-control comparisons of genotype
frequencies, tests of transmission disequilibrium, and log-linear regression models were used to
calculate effect estimates. Spina bifida was associated with over-transmission of the
LEPR
(leptin
receptor) rs1805134 minor C allele (genotype relative risk (GRR): 1.5; 95% confidence interval
(CI): 1.0, 2.1;
P
= 0.0264) and the
COMT
(catechol-O-methyltransferase) rs737865 major T allele
(GRR: 1.4; 95% CI: 1.1, 2.0;
P
= 0.0206). After correcting for multiple comparisons, these
individual test
P
-values exceeded 0.05. Consistent with previous reports, spina bifida was
associated with
MTHFR
677C>T, T (Brachyury) rs3127334,
LEPR
K109R, and
PDGFRA
promoter haplotype combinations. The associations between
LEPR
SNPs and spina bifida suggest
a possible mechanism for the finding that obesity is a NTD risk factor. The association between a
variant in
COMT
and spina bifida implicates methylation and epigenetics in NTDs.
Author's Homepage:
http://people.tcd.ie/amolloyDescription:
PUBLISHED
Author: MOLLOY, ANNE
Type of material:
Journal ArticleCollections
Series/Report no:
American journal of medical genetics. Part A155A
1
Availability:
Full text availableKeywords:
neural tube defects (NTDs)Subject (TCD):
Genes & SocietyDOI:
http://dx.doi.org/10.1002/ajmg.a.33755Metadata
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