Ferreira Manuel A, Vonk Judith M, Baurecht Hansjörg, Marenholz Ingo, Tian Chao, Hoffman Joshua D, Helmer Quinta, Tillander Annika, Ullemar Vilhelmina, van Dongen Jenny, Lu Yi, Rüschendorf Franz, Esparza-Gordillo Jorge, Medway Chris W, Mountjoy Edward, Burrows Kimberley, Hummel Oliver, Grosche Sarah, Brumpton Ben M, Witte John S, Hottenga Jouke-Jan, Willemsen Gonneke, Zheng Jie, Rodríguez Elke, Hotze Melanie, Franke Andre, Revez Joana A, Beesley Jonathan, Matheson Melanie C, Dharmage Shyamali C, Bain Lisa M, Fritsche Lars G, Gabrielsen Maiken E, Balliu Brunilda, Nielsen Jonas B, Zhou Wei, Hveem Kristian, Langhammer Arnulf, Holmen Oddgeir L, Løset Mari, Abecasis Gonçalo R, Willer Cristen J, Arnold Andreas, Homuth Georg, Schmidt Carsten O, Thompson Philip J, Martin Nicholas G, Duffy David L, Novak Natalija, Schulz Holger, Karrasch Stefan, Gieger Christian, Strauch Konstantin, Melles Ronald B, Hinds David A, Hübner Norbert, Weidinger Stephan, Magnusson Patrik K E, Jansen Rick, Jorgenson Eric, Lee Young-Ae, Boomsma Dorret I, Almqvist Catarina, Karlsson Robert, Koppelman Gerard H, Paternoster Lavinia
Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Epidemiology, University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands.
Nat Genet. 2017 Dec;49(12):1752-1757. doi: 10.1038/ng.3985. Epub 2017 Oct 30.
Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.
哮喘、花粉症（或变应性鼻炎）和湿疹（或特应性皮炎）常常在同一个体中同时存在，部分原因是它们有着共同的遗传起源。为了识别共同的风险变异，我们针对一种广泛的过敏性疾病表型开展了一项全基因组关联研究（GWAS；n = 360,838），该表型考虑了这三种疾病中任何一种的存在情况。我们识别出了136个独立的风险变异（P < 3×10），其中包括73个此前未报告的变异，这些变异涉及132个附近的基因参与过敏性疾病的病理生理学过程。仅检测到六个变异具有疾病特异性效应，证实了大多数变异代表共同的风险因素。组织特异性遗传力和生物学过程富集分析表明，共同的风险变异影响淋巴细胞介导的免疫。六个靶基因为药物重新定位提供了机会，而对于36个基因，发现CpG甲基化独立于遗传效应影响转录。哮喘、花粉症和湿疹部分共存是因为它们共享许多遗传风险变异，这些变异会失调免疫相关基因的表达。
