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Medicine (Baltimore). 2018 Mar;97(9):e0043. doi: 10.1097/MD.0000000000010043.

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

Liu X1,2,3,4,5, Hong X6, Tsai HJ3,7,8, Mestan KK9, Shi M10, Kefi A2,11, Hao K12, Chen Q2, Wang G6, Caruso D6, Geng H3,13, Gao Y1,5, He J1, Kumar R14, Wang H2,15, Yu Y2,16, Bartell T2, Tan XD3,13, Schleimer RP17, Weeks DE18, Pongracic JA14, Wang X6,19.

Author information

Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Mary Ann and J. Milburn Smith Child Health Research Program, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago.
Department of Pediatrics.
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
University of Chinese Academy of Sciences, Beijing, China.
Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan.
Department of Public Health, China Medical University, Taichung, Taiwan.
Division of Neonatology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
Biostatistics Branch, NIEHS, NIH, DHHS, Research Triangle Park, NC.
Department of Bioinformatics, the University of Illinois at Chicago, Chicago, IL.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
Center for Intestinal and Liver Inflammation Research, Stanley Manne Children's Research Institute.
Division of Allergy and Immunology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
Department of Cardiovascular Internal Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China.
Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL.
Departments of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
Division of General Pediatrics and Adolescent Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.


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 < 5×10) maternal effect on any FA (rs4235235), which is located in a noncoding RNA (LOC101927947) with unknown function. We also identified 3 suggestive (P < 5×10) 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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