PMID- 29051540 OWN - NLM STAT- MEDLINE DCOM- 20180904 LR - 20211204 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 8 IP - 1 DP - 2017 Oct 20 TI - Genome-wide association study identifies the SERPINB gene cluster as a susceptibility locus for food allergy. PG - 1056 LID - 10.1038/s41467-017-01220-0 [doi] LID - 1056 AB - Genetic factors and mechanisms underlying food allergy are largely unknown. Due to heterogeneity of symptoms a reliable diagnosis is often difficult to make. Here, we report a genome-wide association study on food allergy diagnosed by oral food challenge in 497 cases and 2387 controls. We identify five loci at genome-wide significance, the clade B serpin (SERPINB) gene cluster at 18q21.3, the cytokine gene cluster at 5q31.1, the filaggrin gene, the C11orf30/LRRC32 locus, and the human leukocyte antigen (HLA) region. Stratifying the results for the causative food demonstrates that association of the HLA locus is peanut allergy-specific whereas the other four loci increase the risk for any food allergy. Variants in the SERPINB gene cluster are associated with SERPINB10 expression in leukocytes. Moreover, SERPINB genes are highly expressed in the esophagus. All identified loci are involved in immunological regulation or epithelial barrier function, emphasizing the role of both mechanisms in food allergy. FAU - Marenholz, Ingo AU - Marenholz I AD - Max-Delbruck-Center (MDC) for Molecular Medicine, 13125, Berlin, Germany. AD - Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charite University Medical Center, 13125, Berlin, Germany. FAU - Grosche, Sarah AU - Grosche S AD - Max-Delbruck-Center (MDC) for Molecular Medicine, 13125, Berlin, Germany. AD - Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charite University Medical Center, 13125, Berlin, Germany. FAU - Kalb, Birgit AU - Kalb B AD - Max-Delbruck-Center (MDC) for Molecular Medicine, 13125, Berlin, Germany. AD - Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charite University Medical Center, 13125, Berlin, Germany. AD - Department of Pediatric Pneumology and Immunology, Charite University Medical Center, 13353, Berlin, Germany. FAU - Ruschendorf, Franz AU - Ruschendorf F AUID- ORCID: 0000-0001-5640-810X AD - Max-Delbruck-Center (MDC) for Molecular Medicine, 13125, Berlin, Germany. FAU - Blumchen, Katharina AU - Blumchen K AD - Department of Allergy, Pulmonology and Cystic Fibrosis, Children's Hospital, Goethe University, 60590, Frankfurt am Main, Germany. FAU - Schlags, Rupert AU - Schlags R AD - Department of Pediatric Pneumology and Allergology, Wangen Hospital, 88239, Wangen, Germany. FAU - Harandi, Neda AU - Harandi N AD - Department of Pediatric Pneumology and Allergology, Wangen Hospital, 88239, Wangen, Germany. FAU - Price, Mareike AU - Price M AD - Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625, Hannover, Germany. FAU - Hansen, Gesine AU - Hansen G AD - Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625, Hannover, Germany. FAU - Seidenberg, Jurgen AU - Seidenberg J AD - Department of Pediatric Pneumology and Allergology, Neonatology and Intensive Care, Medical Campus of University Oldenburg, 26133, Oldenburg, Germany. FAU - Roblitz, Holger AU - Roblitz H AD - Department of Pediatrics and Adolescent Medicine, Sana Klinikum Lichtenberg, 10365, Berlin, Germany. FAU - Yurek, Songul AU - Yurek S AD - Department of Pediatric Pneumology and Immunology, Charite University Medical Center, 13353, Berlin, Germany. FAU - Tschirner, Sebastian AU - Tschirner S AD - Department of Pediatric Pneumology and Immunology, Charite University Medical Center, 13353, Berlin, Germany. FAU - Hong, Xiumei AU - Hong X AD - 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, 21205, USA. FAU - Wang, Xiaobin AU - Wang X AD - 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, 21205, USA. FAU - Homuth, Georg AU - Homuth G AD - Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, 17487, Greifswald, Germany. FAU - Schmidt, Carsten O AU - Schmidt CO AD - Institute for Community Medicine, Study of Health in Pomerania/KEF, University Medicine Greifswald, 17475, Greifswald, Germany. FAU - Nothen, Markus M AU - Nothen MM AD - Institute of Human Genetics and Department of Genomics, Life & Brain Center, University of Bonn, 53127, Bonn, Germany. FAU - Hubner, Norbert AU - Hubner N AD - Max-Delbruck-Center (MDC) for Molecular Medicine, 13125, Berlin, Germany. FAU - Niggemann, Bodo AU - Niggemann B AD - Department of Pediatric Pneumology and Immunology, Charite University Medical Center, 13353, Berlin, Germany. FAU - Beyer, Kirsten AU - Beyer K AD - Department of Pediatric Pneumology and Immunology, Charite University Medical Center, 13353, Berlin, Germany. FAU - Lee, Young-Ae AU - Lee YA AD - Max-Delbruck-Center (MDC) for Molecular Medicine, 13125, Berlin, Germany. yolee@mdc-berlin.de. AD - Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charite University Medical Center, 13125, Berlin, Germany. yolee@mdc-berlin.de. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171020 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (FLG protein, human) RN - 0 (Filaggrin Proteins) RN - 0 (Serpins) SB - IM MH - Case-Control Studies MH - Child, Preschool MH - Female MH - Filaggrin Proteins MH - Food Hypersensitivity/*genetics MH - Genetic Predisposition to Disease MH - Genome-Wide Association Study MH - Humans MH - Male MH - Multigene Family MH - Serpins/*genetics PMC - PMC5648765 COIS- The authors declare no competing financial interests. EDAT- 2017/10/21 06:00 MHDA- 2018/09/05 06:00 PMCR- 2017/10/20 CRDT- 2017/10/21 06:00 PHST- 2017/04/07 00:00 [received] PHST- 2017/08/31 00:00 [accepted] PHST- 2017/10/21 06:00 [entrez] PHST- 2017/10/21 06:00 [pubmed] PHST- 2018/09/05 06:00 [medline] PHST- 2017/10/20 00:00 [pmc-release] AID - 10.1038/s41467-017-01220-0 [pii] AID - 1220 [pii] AID - 10.1038/s41467-017-01220-0 [doi] PST - epublish SO - Nat Commun. 2017 Oct 20;8(1):1056. doi: 10.1038/s41467-017-01220-0.