Genome-wide association study of maternal genetic effects and parent-of-origin effects on food allergy

Liu, X.; Hong, X.; Tsai, H. J.; Mestan, K. K.; Shi, M.; Kefi, A.; Hao, K.; Chen, Q.; Wang, G.; Caruso, D.; Geng, H.; Gao, Y.; He, J.; Kumar, R.; Wang, H.; Yu, Y.; Bartell, T.; Tan, X. D.; Schleimer, R. P.; Weeks, D. E.; Pongracic, J. A.; Wang, X.

Medicine (Baltimore). 2018 Mar 1; 97(9):e0043


Previous genetic studies of food allergy (FA) have mainly focused on inherited genotypic effects. The role of parental genotypic effects remains largely unexplored. Leveraging existing genome-wide association study (GWAS) data generated from the Chicago Food Allergy Study, we examined maternal genotypic and parent-of-origin (PO) effects using multinomial likelihood ratio tests in 588 complete and incomplete Caucasian FA trios. We identified 1 single nucleotide polymorphism with significant (P < 5x10) maternal effect on any FA (rs4235235), which is located in a noncoding RNA (LOC101927947) with unknown function. We also identified 3 suggestive (P < 5x10) loci with maternal genetic effects: 1 for any FA (rs976078, in a gene desert region on 13q31.1) and 2 for egg allergy (rs1343795 and rs4572450, in the ZNF652 gene, where genetic variants have been associated with atopic dermatitis). Three suggestive loci with PO effect were observed: 1 for peanut allergy (rs4896888 in the ADGB gene) and 2 for any FA in boys only (rs1036504 and rs2917750 in the IQCE gene). Findings from this family-based GWAS of FA provided some preliminary evidence on maternal genotypic or PO effects on FA. Additional family-based studies are needed to confirm our findings and gain new insight into maternal and paternal genetic contribution to FA.

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