Variants of DENND1B Associated with Asthma in Children

作者：Patrick Sleiman, James H. Flory, Marcin Imieliński, Jonathan P. Bradfield, Kiran Annaiah, Saffron A.G. Willis‐Owen, Kai Wang, Nicholas Rafaels, Sven Michel, Klaus Bønnelykke, Haitao Zhang, Cecilia E. Kim, Edward C. Frackelton, Joseph Glessner, Cuiping Hou, F. George Otieno, Erin Santa, Kelly Thomas, Ryan M. Smith, Wendy Glaberson, Maria Garris, Rosetta Chiavacci, Terri H. Beaty, Ingo Ruczinski, Jordan S. Orange, Julian L. Allen, Jonathan M. Spergel, Robert W. Grundmeier, Rasika A. Mathias, Jason D. Christie, Erika von Mutius, William Cookson, Michael Kabesch, Miriam F. Moffatt, Michael Grunstein, Kathleen C. Barnes, Marcella Devoto, Mark Magnusson, Hongzhe Li, Struan F.A. Grant, Hans Bisgaard, Håkon Håkonarson · 发表于：New England Journal of Medicine · 年份：2009 · DOI：10.1056/nejmoa0901867 · 被引用次数：319 · 研究领域：Asthma and respiratory diseases、IL-33, ST2, and ILC Pathways、Genetic Associations and Epidemiology

BACKGROUND: Asthma is a complex disease that has genetic and environmental causes. The genetic factors associated with susceptibility to asthma remain largely unknown. METHODS: We carried out a genomewide association study involving children with asthma. The sample included 793 North American children of European ancestry with persistent asthma who required daily inhaled glucocorticoid therapy and 1988 matched controls (the discovery set). We also tested for genomewide association in an independent cohort of 917 persons of European ancestry who had asthma and 1546 matched controls (the replication set). Finally, we tested for an association between 20 single-nucleotide polymorphisms (SNPs) at chromosome 1q31 and asthma in 1667 North American children of African ancestry who had asthma and 2045 ancestrally matched controls. RESULTS: In our meta-analysis of all samples from persons of European ancestry, we observed an association, with genomewide significance, between asthma and SNPs at the previously reported locus on 17q21 and an additional eight SNPs at a novel locus on 1q31. The SNP most strongly associated with asthma was rs2786098 (P=8.55x10(-9)). We observed replication of the association of asthma with SNP rs2786098 in the independent series of persons of European ancestry (combined P=9.3x10(-11)). The alternative allele of each of the eight SNPs on chromosome 1q31 was strongly associated with asthma in the children of African ancestry (P=1.6x10(-13) for the comparison ...