Maternal genetic markers for risk of celiac disease and their potential association with neural tube defects in offspring

Mol Genet Genomic Med. 2019 Jun;7(6):e688. doi: 10.1002/mgg3.688. Epub 2019 Apr 9.


Background: We examined the association between the maternal genotype for celiac disease-associated variants and risk of neural tube defects (NTDs).

Methods: We conducted a case-control study, using data from the National Birth Defects Prevention Study. We evaluated 667 cases (women with an offspring with NTD) and 743 controls (women with an offspring without a birth defect). We classified women as having low, intermediate, or high risk of celiac disease based on human leukocyte antigen (HLA) variants. We used logistic regression to assess the relationship between HLA celiac risk group (low, intermediate, high) and risk of NTDs. Fifteen non-HLA variants (identified from genome-wide association studies of celiac disease) were individually evaluated and modeled additively.

Results: There was no association between HLA celiac risk group and NTDs (intermediate vs. low risk: aOR, 1.0; 95% CI, 0.8-1.3; high vs. low risk: aOR, 0.8; 95% CI, 0.5-1.3). Of the fifteen non-HLA variants, we observed five significant associations after accounting for multiple comparisons. Three negative associations were observed with rs10903122, rs13314993, rs13151961 (aOR range: 0.69-0.81), and two positive associations were observed with rs13003464 and rs11221332 (aOR range: 1.27-1.73).

Conclusion: If confirmed, our results suggest that the maternal variants related to celiac disease may be involved in the risk of NTDs.

Keywords: candidate genes; celiac disease; human leukocyte antigen; neural tube defects; pregnancy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Celiac Disease / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • HLA Antigens / genetics*
  • Humans
  • Infant, Newborn
  • Male
  • Neural Tube Defects / epidemiology*
  • Neural Tube Defects / genetics
  • Polymorphism, Single Nucleotide


  • HLA Antigens