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Evidence from mouse models indicates that the tumor protein p53 (<jats:italic>TP53<\/jats:italic>) is involved in implantation and normal neural tube development. To determine whether genetic variation in<jats:italic>TP53<\/jats:italic>might contribute to NTD risk in humans, we constructed a high resolution linkage disequilibrium (LD) map of the<jats:italic>TP53<\/jats:italic>genomic region based on genotyping 21 markers in an Irish population. We found that nine of these variants can be used to capture the majority of common variation in the<jats:italic>TP53<\/jats:italic>genomic region. In contrast, the 3\u2010marker haplotype commonly reported in the<jats:italic>TP53<\/jats:italic>literature offers limited coverage of the variation in the gene. We used the expanded set of polymorphisms to measure the influence of<jats:italic>TP53<\/jats:italic>on NTDs using both case\u2013control and family based tests of association. We also assayed a functional variant in the p53 regulator<jats:italic>MDM2<\/jats:italic>(rs2279744). Alleles of three noncoding<jats:italic>TP53<\/jats:italic>markers were associated with NTD risk. A case effect was seen with the GG genotype of rs1625895 in intron 6 (OR\u2009=\u20091.37 [1.04\u20131.79],<jats:italic>P<\/jats:italic>\u2009=\u20090.02). A maternal effect was seen with the 135\/135 genotype of the intron 1 VNTR (OR\u2009=\u20091.86 [1.16\u20132.96],<jats:italic>P<\/jats:italic>\u2009=\u20090.01) and the TT genotype of rs1614984 (RR\u2009=\u20090.58 [0.37\u20130.91],<jats:italic>P<\/jats:italic>\u2009=\u20090.02). As multiple comparisons were made, these cannot be considered definitive positive findings and additional investigation is required. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.32504","type":"journal-article","created":{"date-parts":[[2008,9,16]],"date-time":"2008-09-16T21:23:22Z","timestamp":1221600202000},"page":"2617-2625","source":"Crossref","is-referenced-by-count":15,"title":["Construction of a high resolution linkage disequilibrium map to evaluate common genetic variation in<i>TP53<\/i>and neural tube defect risk in an Irish 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