Candidate gene analysis in human neural tube defects

AbstractBiochemical and developmental pathways, mouse models, and positional evidence have provided numerous candidate genes for the study of human neural tube defects. In a survey of 80 studies on 38 candidate genes, few found significant results in human populations through case‐control or family‐based association studies. While the folate pathway has been explored extensively, only theMTHFR677C > T polymorphism was significant, and only in an Irish population. Developmental pathways such as the Wnt signaling pathway andHoxgenes have also been explored without positive results. More than 90 mouse candidates have been identified through spontaneous and knockout mutations, but only the T locus (mouseBrachyurygene) showed association in an initial study that was not confirmed on follow‐up. Positional candidates have been derived from cytogenetic evidence, but preliminary genomic screens have limited power due to small sample sizes. Future studies would increase their power to detect association by using more samples. In addition a clarification of the phenotype would be beneficial as many studies used different inclusion criteria. Incorporating several types of data could highlig