A genetic signature of spina bifida risk from pathway-informed comprehensive gene-variant analysis.

ABSTRACT: Despite compelling epidemiological evidence that folic acid supplements reduce the frequency of neural tube defects (NTDs) in newborns, common variant association studies with folate metabolism genes have failed to explain the majority of NTD risk. The contribution of rare alleles as well as genetic interactions within the folate pathway have not been extensively studied in the context of NTDs. Thus, we sequenced the exons in 31 folate-related genes in a 480-member NTD case-control population to identify the full spectrum of allelic variation and determine whether rare alleles or obvious genetic interactions within this pathway affect NTD risk. We constructed a pathway model, predetermined independent of the data, which grouped genes into coherent sets reflecting the distinct metabolic com

SUBMITTER: Marini NJ 

PROVIDER: S-EPMC3227667 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature