OBJECTIVE: Genome-wide association studies (GWASs) have identified genes associated with asthma, however expression of these genes in asthma-relevant tissues has not been studied. This study tested expression and correlation between GWAS-identified asthma genes and asthma or asthma severity. METHODS: Correlation analyses of expression levels of GWAS-identified asthma genes and asthma-related biomarkers were performed in cells from human bronchial epithelial biopsy (BEC, n = 107) and bronchial alveolar lavage (BAL, n = 94). RESULTS: Expression levels of asthma genes between BEC and BAL and with asthma or asthma severity were weakly correlated. The expression levels of IL18R1 were consistently higher in asthma than controls or in severe asthma than mild/moderate asthma in BEC and BAL (p < 0.05). In RAD50-IL13 region, the expression levels of RAD50, not IL4, IL5, or IL13, were positively correlated between BEC and BAL (ρ = 0.53, P = 4.5 × 10(-6)). The expression levels of IL13 were positively correlated with IL5 in BEC (ρ = 0.35, P = 1.9 × 10(-4)) and IL4 in BAL (ρ = 0.42, P = 2.5 × 10(-5)), respectively. rs3798134 in RAD50, a GWAS-identified SNP, was correlated with IL13 expression and the expression levels of IL13 were correlated with asthma (P = 0.03). rs17772583 in RAD50 was significantly correlated with RAD50 expression in BAL and BEC (P = 7.4 × 10(-7) and 0.04) but was not associated with asthma. CONCLUSIONS: This is the first report studying the expression of GWAS-identified asthma genes in BEC and BAL. IL13, rather than RAD50, IL4, or IL5, is more likely to be the asthma susceptibility gene. Our study illustrates tissue-specific expression of asthma-related genes. Therefore, whenever possible, disease-relevant tissues should be used for transcription analysis.
OBJECTIVE: Genome-wide association studies (GWASs) have identified genes associated with asthma, however expression of these genes in asthma-relevant tissues has not been studied. This study tested expression and correlation between GWAS-identified asthma genes and asthma or asthma severity. METHODS: Correlation analyses of expression levels of GWAS-identified asthma genes and asthma-related biomarkers were performed in cells from human bronchial epithelial biopsy (BEC, n = 107) and bronchial alveolar lavage (BAL, n = 94). RESULTS: Expression levels of asthma genes between BEC and BAL and with asthma or asthma severity were weakly correlated. The expression levels of IL18R1 were consistently higher in asthma than controls or in severe asthma than mild/moderate asthma in BEC and BAL (p < 0.05). In RAD50-IL13 region, the expression levels of RAD50, not IL4, IL5, or IL13, were positively correlated between BEC and BAL (ρ = 0.53, P = 4.5 × 10(-6)). The expression levels of IL13 were positively correlated with IL5 in BEC (ρ = 0.35, P = 1.9 × 10(-4)) and IL4 in BAL (ρ = 0.42, P = 2.5 × 10(-5)), respectively. rs3798134 in RAD50, a GWAS-identified SNP, was correlated with IL13 expression and the expression levels of IL13 were correlated with asthma (P = 0.03). rs17772583 in RAD50 was significantly correlated with RAD50 expression in BAL and BEC (P = 7.4 × 10(-7) and 0.04) but was not associated with asthma. CONCLUSIONS: This is the first report studying the expression of GWAS-identified asthma genes in BEC and BAL. IL13, rather than RAD50, IL4, or IL5, is more likely to be the asthma susceptibility gene. Our study illustrates tissue-specific expression of asthma-related genes. Therefore, whenever possible, disease-relevant tissues should be used for transcription analysis.
Authors: Lucia A Hindorff; Praveen Sethupathy; Heather A Junkins; Erin M Ramos; Jayashri P Mehta; Francis S Collins; Teri A Manolio Journal: Proc Natl Acad Sci U S A Date: 2009-05-27 Impact factor: 11.205
Authors: Xingnan Li; Gregory A Hawkins; Elizabeth J Ampleford; Wendy C Moore; Huashi Li; Annette T Hastie; Timothy D Howard; Homer A Boushey; William W Busse; William J Calhoun; Mario Castro; Serpil C Erzurum; Elliot Israel; Robert F Lemanske; Stanley J Szefler; Stephen I Wasserman; Sally E Wenzel; Stephen P Peters; Deborah A Meyers; Eugene R Bleecker Journal: J Allergy Clin Immunol Date: 2013-03-28 Impact factor: 10.793
Authors: X Li; A T Hastie; G A Hawkins; W C Moore; E J Ampleford; J Milosevic; H Li; W W Busse; S C Erzurum; N Kaminski; S E Wenzel; D A Meyers; E R Bleecker Journal: Allergy Date: 2015-07-24 Impact factor: 13.146
Authors: Xingnan Li; Elizabeth J Ampleford; Timothy D Howard; Wendy C Moore; Dara G Torgerson; Huashi Li; William W Busse; Mario Castro; Serpil C Erzurum; Elliot Israel; Dan L Nicolae; Carole Ober; Sally E Wenzel; Gregory A Hawkins; Eugene R Bleecker; Deborah A Meyers Journal: J Allergy Clin Immunol Date: 2012-06-12 Impact factor: 10.793
Authors: Jingyuan Fu; Marcel G M Wolfs; Patrick Deelen; Harm-Jan Westra; Rudolf S N Fehrmann; Gerard J Te Meerman; Wim A Buurman; Sander S M Rensen; Harry J M Groen; Rinse K Weersma; Leonard H van den Berg; Jan Veldink; Roel A Ophoff; Harold Snieder; David van Heel; Ritsert C Jansen; Marten H Hofker; Cisca Wijmenga; Lude Franke Journal: PLoS Genet Date: 2012-01-19 Impact factor: 5.917
Authors: Miriam F Moffatt; Michael Kabesch; Liming Liang; Anna L Dixon; David Strachan; Simon Heath; Martin Depner; Andrea von Berg; Albrecht Bufe; Ernst Rietschel; Andrea Heinzmann; Burkard Simma; Thomas Frischer; Saffron A G Willis-Owen; Kenny C C Wong; Thomas Illig; Christian Vogelberg; Stephan K Weiland; Erika von Mutius; Gonçalo R Abecasis; Martin Farrall; Ivo G Gut; G Mark Lathrop; William O C Cookson Journal: Nature Date: 2007-07-04 Impact factor: 49.962
Authors: Anu Laulajainen-Hongisto; Annina Lyly; Paula Kauppi; Sanna Toppila-Salmi; Tanzeela Hanif; Kishor Dhaygude; Matti Kankainen; Risto Renkonen; Kati Donner; Pirkko Mattila; Tuomas Jartti; Jean Bousquet Journal: Clin Transl Allergy Date: 2020-10-28 Impact factor: 5.871
Authors: Sierra R Bruno; Amit Kumar; Zoe F Mark; Ravishankar Chandrasekaran; Emily Nakada; Nicolas Chamberlain; Bethany Mihavics; Joseph Walzer; Jonathon Cahoon; Anne E Dixon; Brian Cunniff; Vikas Anathy Journal: Int J Mol Sci Date: 2021-10-15 Impact factor: 6.208
Authors: Stephany Sánchez-Ovando; Stelios Pavlidis; Nazanin Zounemat Kermani; Katherine Joanne Baines; Daniel Barker; Peter G Gibson; Lisa G Wood; Ian M Adcock; Kian Fan Chung; Jodie Louise Simpson; Peter A B Wark Journal: Respirology Date: 2022-06-07 Impact factor: 6.175