D J Martino1, S Ashley1,2, J Koplin1,3, J Ellis1, R Saffery1, S C Dharmage3, L Gurrin3, M C Matheson3, B Kalb4,5,6, I Marenholz5,6, K Beyer4, Y-A Lee5,6, X Hong7, X Wang7, D Vukcevic1,8, A Motyer1,8, S Leslie1,8, K J Allen1, M A R Ferreira9. 1. Department of Paediatrics, Murdoch Childrens Research Institute, The Royal Children's Hospital, The University of Melbourne, Melbourne, Vic., Australia. 2. Hudson Institute of Medical Research, Clayton, Vic., Australia. 3. School of Population and Global Health, The University of Melbourne, Melbourne, Vic., Australia. 4. Pediatric Pneumology and Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany. 5. Clinic for Pediatric Allergy, Experimental and Clinical Research Center of MDC, Charité, Berlin, Germany. 6. Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany. 7. 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, USA. 8. Centre for Systems Genomics, Schools of Mathematics and Statistics and Biosciences, The University of Melbourne, Melbourne, Vic., Australia. 9. QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia.
Abstract
BACKGROUND: Genetic variants for IgE-mediated peanut allergy are yet to be fully characterized and to date only one genomewide association study (GWAS) has been published. OBJECTIVE: To identify genetic variants associated with challenge-proven peanut allergy. METHODS: We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants (all ~ 1 year old). We tested a total of 3.8 million single nucleotide polymorphisms, as well as imputed HLA alleles and amino acids. Replication was assessed by de novo genotyping in a panel of additional 117 cases and 380 controls, and in silico testing in two independent GWAS cohorts. RESULTS: We identified 21 independent associations at P ≤ 5 × 10-5 but were unable to replicate these. The most significant HLA association was the previously reported amino acid variant located at position 71, within the peptide-binding groove of HLA-DRB1 (P = 2 × 10-4 ). Our study therefore reproduced previous findings for the association between peanut allergy and HLA-DRB1 in this Australian population. CONCLUSIONS AND CLINICAL RELEVANCE: Genetic determinants for challenge-proven peanut allergy include alleles at the HLA-DRB1 locus.
BACKGROUND: Genetic variants for IgE-mediated peanutallergy are yet to be fully characterized and to date only one genomewide association study (GWAS) has been published. OBJECTIVE: To identify genetic variants associated with challenge-proven peanutallergy. METHODS: We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanutallergy against 148 non-allergic infants (all ~ 1 year old). We tested a total of 3.8 million single nucleotide polymorphisms, as well as imputed HLA alleles and amino acids. Replication was assessed by de novo genotyping in a panel of additional 117 cases and 380 controls, and in silico testing in two independent GWAS cohorts. RESULTS: We identified 21 independent associations at P ≤ 5 × 10-5 but were unable to replicate these. The most significant HLA association was the previously reported amino acid variant located at position 71, within the peptide-binding groove of HLA-DRB1 (P = 2 × 10-4 ). Our study therefore reproduced previous findings for the association between peanutallergy and HLA-DRB1 in this Australian population. CONCLUSIONS AND CLINICAL RELEVANCE: Genetic determinants for challenge-proven peanutallergy include alleles at the HLA-DRB1 locus.
Authors: Leah C Kottyan; Michael P Trimarchi; Xiaoming Lu; Julie M Caldwell; Avery Maddox; Sreeja Parameswaran; Michael Lape; Rahul J D'Mello; Madeline Bonfield; Adina Ballaban; Vincent Mukkada; Philip E Putnam; Pablo Abonia; Netali Ben-Baruch Morgenstern; Amy A Eapen; Ting Wen; Matthew T Weirauch; Marc E Rothenberg Journal: J Allergy Clin Immunol Date: 2020-10-23 Impact factor: 14.290
Authors: Manuel A R Ferreira; Judith M Vonk; Hansjörg Baurecht; Ingo Marenholz; Chao Tian; Joshua D Hoffman; Quinta Helmer; Annika Tillander; Vilhelmina Ullemar; Yi Lu; Sarah Grosche; Franz Rüschendorf; Raquel Granell; Ben M Brumpton; Lars G Fritsche; Laxmi Bhatta; Maiken E Gabrielsen; Jonas B Nielsen; Wei Zhou; Kristian Hveem; Arnulf Langhammer; Oddgeir L Holmen; Mari Løset; Gonçalo R Abecasis; Cristen J Willer; Nima C Emami; Taylor B Cavazos; John S Witte; Agnieszka Szwajda; David A Hinds; Norbert Hübner; Stephan Weidinger; Patrik Ke Magnusson; Eric Jorgenson; Robert Karlsson; Lavinia Paternoster; Dorret I Boomsma; Catarina Almqvist; Young-Ae Lee; Gerard H Koppelman Journal: PLoS Genet Date: 2020-06-30 Impact factor: 5.917