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For the remaining 33 SNPs genotyped on the Illumina GoldenGate platform, 314 case families and 338 controls were tested (Table II). The genotype distribution for each SNP was obtained for controls, cases, case-mothers, and case-fathers (see supporting information Table II which may be found in the online version of this article). For the six SNPs that we previously investigated, we increased the size of the case group by 100 or more subjects, compared with our earlier reports. In case-control analysis, spina bifida was associated with homozygosity for the MTHFR 677C>T (rs1801133, A222V) minor T allele (OR: 1.3; 95% CI: 1.0�C1.6; P?=?0.0451). The T (Brachyury) rs3127334 major A allele was also associated with spina bifida in case-control analysis (OR: 2.4; 95% CI: 1.1�C5.7; P?=?0.0288; dominant model). There was no association with MTHFR 1298A>C SCH772984 in vitro (rs1801131, E429A), MTR D919G (rs1805087), UCP2 ?866G>A (rs659366), and UCP2 A55V (rs660339), similar to our previous reports. Our results for variants reported to be NTD risk factors by other groups (Table III) show that spina bifida was associated with transmission of the LEPR (leptin receptor) rs1137100 (K109R) major A allele (GRR: 1.4; 95% CI: 1.0�C1.8; P?=?0.0236) and with PDGFRA (platelet-derived growth factor receptor, alpha polypeptide) haplotype click here combinations with high-transcriptional activity (OR: 1.5; 95% CI: 1.0�C2.0); P?=?0.0252; recessive effect). No association with spina bifida was observed for the other SNPs reported in previous studies. We examined associations for the other 46 SNPs that either showed no association with NTDs in Ritonavir previous reports or were not tested previously for an association with NTDs (see supporting information Tables III and IV which may be found in the online version of this article); 8 were associated with spina bifida (Table IV). Two of these SNPs were associated with spina bifida based on the results of two different statistical tests. Increased spina bifida risk was associated with the LEPR rs1805134 minor C allele when tested using the TDT (GRR: 1.5; 95% CI: 1.0�C2.1; P?=?0.0264) and log-linear analysis (GRR: 1.7; 95% CI: 1.1�C2.6; P?=?0.0179), and with the COMT rs737865 major T allele when tested using the TDT (GRR: 1.4; 95% CI: 1.1�C2.0; P?=?0.0206) and log-linear analysis (GRR: 2.1; 95% CI: 1.1�C4.3; P?=?0.0364). Correction for multiple comparisons performed for the 46 SNPs rendered these P-values >0.05. Adding case families with other NTDs produced few changes in the results obtained. Multiple SNPs in BRCA1 and LEPR that showed an association with spina bifida did not exhibit intragenic LD. BRCA1 rs1799966 and rs799917 were in strong LD (r2?=?0.97); neither was in strong LD with BRCA1 rs3737559 (r2?