Replication and exploratory analysis of 24 candidate risk polymorphisms for neural tube defects

Hdl Handle:
http://hdl.handle.net/10147/335868
Title:
Replication and exploratory analysis of 24 candidate risk polymorphisms for neural tube defects
Authors:
Pangilinan, Faith; Molloy, Anne M; Mills, James L; Troendle, James F; Parle-McDermott, Anne; Kay, Denise M; Browne, Marilyn L; McGrath, Emily C; Abaan, Hatice O; Sutton, Marie; Kirke, Peadar N; Caggana, Michele; Shane, Barry; Scott, John M; Brody, Lawrence C
Citation:
Pangilinan, F. et al., 2014. Replication and exploratory analysis of 24 candidate risk polymorphisms for neural tube defects. BMC Medical Genetics, 15 (1) p 102
Issue Date:
8-Oct-2014
URI:
http://dx.doi.org/10.1186/s12881-014-0102-9; http://hdl.handle.net/10147/335868
Abstract:
Abstract Background Neural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population. Methods Replication tests of 24 nominally significant NTD associations were performed in racially/ethnically matched populations. Family-based tests of fifteen nominally significant single nucleotide polymorphisms (SNPs) were repeated in a cohort of NTD trios (530 cases and their parents) from the United Kingdom, and case–control tests of nine nominally significant SNPs were repeated in a cohort (190 cases, 941 controls) from New York State (NYS). Secondary hypotheses involved evaluating the latter set of nine SNPs for NTD association using alternate case–control models and NTD groupings in white, African American and Hispanic cohorts from NYS. Results Of the 24 SNPs tested for replication, ADA rs452159 and MTR rs10925260 were significantly associated with isolated NTDs. Of the secondary tests performed, ARID1A rs11247593 was associated with NTDs in whites, and ALDH1A2 rs7169289 was associated with isolated NTDs in African Americans. Conclusions We report a number of associations between SNP genotypes and neural tube defects. These associations were nominally significant before correction for multiple hypothesis testing. These corrections are highly conservative for association studies of untested hypotheses, and may be too conservative for replication studies. We therefore believe the true effect of these four nominally significant SNPs on NTD risk will be more definitively determined by further study in other populations, and eventual meta-analysis.
Language:
en
Keywords:
GENETICS; NEONATE
Local subject classification:
BIRTH DEFECTS

Full metadata record

DC FieldValue Language
dc.contributor.authorPangilinan, Faithen_GB
dc.contributor.authorMolloy, Anne Men_GB
dc.contributor.authorMills, James Len_GB
dc.contributor.authorTroendle, James Fen_GB
dc.contributor.authorParle-McDermott, Anneen_GB
dc.contributor.authorKay, Denise Men_GB
dc.contributor.authorBrowne, Marilyn Len_GB
dc.contributor.authorMcGrath, Emily Cen_GB
dc.contributor.authorAbaan, Hatice Oen_GB
dc.contributor.authorSutton, Marieen_GB
dc.contributor.authorKirke, Peadar Nen_GB
dc.contributor.authorCaggana, Micheleen_GB
dc.contributor.authorShane, Barryen_GB
dc.contributor.authorScott, John Men_GB
dc.contributor.authorBrody, Lawrence Cen_GB
dc.date.accessioned2014-11-20T10:11:57Z-
dc.date.available2014-11-20T10:11:57Z-
dc.date.issued2014-10-08-
dc.identifier.citationPangilinan, F. et al., 2014. Replication and exploratory analysis of 24 candidate risk polymorphisms for neural tube defects. BMC Medical Genetics, 15 (1) p 102en_GB
dc.identifier.urihttp://dx.doi.org/10.1186/s12881-014-0102-9-
dc.identifier.urihttp://hdl.handle.net/10147/335868-
dc.description.abstractAbstract Background Neural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population. Methods Replication tests of 24 nominally significant NTD associations were performed in racially/ethnically matched populations. Family-based tests of fifteen nominally significant single nucleotide polymorphisms (SNPs) were repeated in a cohort of NTD trios (530 cases and their parents) from the United Kingdom, and case–control tests of nine nominally significant SNPs were repeated in a cohort (190 cases, 941 controls) from New York State (NYS). Secondary hypotheses involved evaluating the latter set of nine SNPs for NTD association using alternate case–control models and NTD groupings in white, African American and Hispanic cohorts from NYS. Results Of the 24 SNPs tested for replication, ADA rs452159 and MTR rs10925260 were significantly associated with isolated NTDs. Of the secondary tests performed, ARID1A rs11247593 was associated with NTDs in whites, and ALDH1A2 rs7169289 was associated with isolated NTDs in African Americans. Conclusions We report a number of associations between SNP genotypes and neural tube defects. These associations were nominally significant before correction for multiple hypothesis testing. These corrections are highly conservative for association studies of untested hypotheses, and may be too conservative for replication studies. We therefore believe the true effect of these four nominally significant SNPs on NTD risk will be more definitively determined by further study in other populations, and eventual meta-analysis.-
dc.language.isoenen
dc.subjectGENETICSen_GB
dc.subjectNEONATEen_GB
dc.subject.otherBIRTH DEFECTSen_GB
dc.titleReplication and exploratory analysis of 24 candidate risk polymorphisms for neural tube defectsen_GB
dc.language.rfc3066en-
dc.rights.holderFaith Pangilinan et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2014-10-14T11:12:52Z-
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