BACKGROUND: Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear. OBJECTIVE: We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings. METHOD: Approximately 2.2 million genotyped or imputed single nucleotide polymorphisms were investigated in 4 large European adult cohorts for AR (3,933 self-reported cases vs 8,965 control subjects) and grass sensitization (2,315 cases vs 10,032 control subjects). RESULTS: Three loci reached genome-wide significance for either phenotype. The HLA variant rs7775228, which cis-regulates HLA-DRB4, was strongly associated with grass sensitization and weakly with AR (P(grass) = 1.6 × 10(-9); P(AR) = 8.0 × 10(-3)). Variants in a locus near chromosome 11 open reading frame 30 (C11orf30) and leucine-rich repeat containing 32 (LRRC32), which was previously associated with atopic dermatitis and eczema, were also strongly associated with both phenotypes (rs2155219; P(grass) = 9.4 × 10(-9); P(AR) = 3.8 × 10(-8)). The third genome-wide significant variant was rs17513503 (P(grass) = 1.2 × 10(-8); PAR = 7.4 × 10(-7)) which was located near transmembrane protein 232 (TMEM232) and solute carrier family 25, member 46 (SLC25A46). Twelve further loci with suggestive associations were also identified. Using a candidate gene approach, where we considered variants within 164 genes previously thought to be important, we found variants in 3 further genes that may be of interest: thymic stromal lymphopoietin (TSLP), Toll-like receptor 6 (TLR6) and nucleotide-binding oligomerization domain containing 1 (NOD1/CARD4). We found no evidence for variants that modified the effect of birth order on either phenotype. CONCLUSIONS: This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses.
BACKGROUND: Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear. OBJECTIVE: We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings. METHOD: Approximately 2.2 million genotyped or imputed single nucleotide polymorphisms were investigated in 4 large European adult cohorts for AR (3,933 self-reported cases vs 8,965 control subjects) and grass sensitization (2,315 cases vs 10,032 control subjects). RESULTS: Three loci reached genome-wide significance for either phenotype. The HLA variant rs7775228, which cis-regulates HLA-DRB4, was strongly associated with grass sensitization and weakly with AR (P(grass) = 1.6 × 10(-9); P(AR) = 8.0 × 10(-3)). Variants in a locus near chromosome 11 open reading frame 30 (C11orf30) and leucine-rich repeat containing 32 (LRRC32), which was previously associated with atopic dermatitis and eczema, were also strongly associated with both phenotypes (rs2155219; P(grass) = 9.4 × 10(-9); P(AR) = 3.8 × 10(-8)). The third genome-wide significant variant was rs17513503 (P(grass) = 1.2 × 10(-8); PAR = 7.4 × 10(-7)) which was located near transmembrane protein 232 (TMEM232) and solute carrier family 25, member 46 (SLC25A46). Twelve further loci with suggestive associations were also identified. Using a candidate gene approach, where we considered variants within 164 genes previously thought to be important, we found variants in 3 further genes that may be of interest: thymic stromal lymphopoietin (TSLP), Toll-like receptor 6 (TLR6) and nucleotide-binding oligomerization domain containing 1 (NOD1/CARD4). We found no evidence for variants that modified the effect of birth order on either phenotype. CONCLUSIONS: This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses.
Authors: Johannes Waage; Marie Standl; John A Curtin; Leon E Jessen; Jonathan Thorsen; Chao Tian; Nathan Schoettler; Carlos Flores; Abdel Abdellaoui; Tarunveer S Ahluwalia; Alexessander C Alves; Andre F S Amaral; Josep M Antó; Andreas Arnold; Amalia Barreto-Luis; Hansjörg Baurecht; Catharina E M van Beijsterveldt; Eugene R Bleecker; Sílvia Bonàs-Guarch; Dorret I Boomsma; Susanne Brix; Supinda Bunyavanich; Esteban G Burchard; Zhanghua Chen; Ivan Curjuric; Adnan Custovic; Herman T den Dekker; Shyamali C Dharmage; Julia Dmitrieva; Liesbeth Duijts; Markus J Ege; W James Gauderman; Michel Georges; Christian Gieger; Frank Gilliland; Raquel Granell; Hongsheng Gui; Torben Hansen; Joachim Heinrich; John Henderson; Natalia Hernandez-Pacheco; Patrick Holt; Medea Imboden; Vincent W V Jaddoe; Marjo-Riitta Jarvelin; Deborah L Jarvis; Kamilla K Jensen; Ingileif Jónsdóttir; Michael Kabesch; Jaakko Kaprio; Ashish Kumar; Young-Ae Lee; Albert M Levin; Xingnan Li; Fabian Lorenzo-Diaz; Erik Melén; Josep M Mercader; Deborah A Meyers; Rachel Myers; Dan L Nicolae; Ellen A Nohr; Teemu Palviainen; Lavinia Paternoster; Craig E Pennell; Göran Pershagen; Maria Pino-Yanes; Nicole M Probst-Hensch; Franz Rüschendorf; Angela Simpson; Kari Stefansson; Jordi Sunyer; Gardar Sveinbjornsson; Elisabeth Thiering; Philip J Thompson; Maties Torrent; David Torrents; Joyce Y Tung; Carol A Wang; Stephan Weidinger; Scott Weiss; Gonneke Willemsen; L Keoki Williams; Carole Ober; David A Hinds; Manuel A Ferreira; Hans Bisgaard; David P Strachan; Klaus Bønnelykke Journal: Nat Genet Date: 2018-07-16 Impact factor: 38.330
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Authors: Sarah K Wise; Sandra Y Lin; Elina Toskala; Richard R Orlandi; Cezmi A Akdis; Jeremiah A Alt; Antoine Azar; Fuad M Baroody; Claus Bachert; G Walter Canonica; Thomas Chacko; Cemal Cingi; Giorgio Ciprandi; Jacquelynne Corey; Linda S Cox; Peter Socrates Creticos; Adnan Custovic; Cecelia Damask; Adam DeConde; John M DelGaudio; Charles S Ebert; Jean Anderson Eloy; Carrie E Flanagan; Wytske J Fokkens; Christine Franzese; Jan Gosepath; Ashleigh Halderman; Robert G Hamilton; Hans Jürgen Hoffman; Jens M Hohlfeld; Steven M Houser; Peter H Hwang; Cristoforo Incorvaia; Deborah Jarvis; Ayesha N Khalid; Maritta Kilpeläinen; Todd T Kingdom; Helene Krouse; Desiree Larenas-Linnemann; Adrienne M Laury; Stella E Lee; Joshua M Levy; Amber U Luong; Bradley F Marple; Edward D McCoul; K Christopher McMains; Erik Melén; James W Mims; Gianna Moscato; Joaquim Mullol; Harold S Nelson; Monica Patadia; Ruby Pawankar; Oliver Pfaar; Michael P Platt; William Reisacher; Carmen Rondón; Luke Rudmik; Matthew Ryan; Joaquin Sastre; Rodney J Schlosser; Russell A Settipane; Hemant P Sharma; Aziz Sheikh; Timothy L Smith; Pongsakorn Tantilipikorn; Jody R Tversky; Maria C Veling; De Yun Wang; Marit Westman; Magnus Wickman; Mark Zacharek Journal: Int Forum Allergy Rhinol Date: 2018-02 Impact factor: 3.858
Authors: August Blackburn; Harald H H Göring; Angela Dean; Melanie A Carless; Thomas Dyer; Satish Kumar; Sharon Fowler; Joanne E Curran; Laura Almasy; Michael Mahaney; Anthony Comuzzie; Ravindranath Duggirala; John Blangero; Donna M Lehman Journal: Eur J Hum Genet Date: 2012-08-22 Impact factor: 4.246