Age-of-onset information helps identify 76 genetic variants associated with allergic disease
Autoři:
Manuel A. R. Ferreira aff001; Judith M. Vonk aff002; Hansjörg Baurecht aff003; Ingo Marenholz aff005; Chao Tian aff007; Joshua D. Hoffman aff008; Quinta Helmer aff009; Annika Tillander aff010; Vilhelmina Ullemar aff010; Yi Lu aff010; Sarah Grosche aff005; Franz Rüschendorf aff005; Raquel Granell aff012; Ben M. Brumpton aff012; Lars G. Fritsche aff013; Laxmi Bhatta aff013; Maiken E. Gabrielsen aff013; Jonas B. Nielsen aff016; Wei Zhou aff017; Kristian Hveem aff013; Arnulf Langhammer aff018; Oddgeir L. Holmen aff013; Mari Løset aff013; Gonçalo R. Abecasis aff013; Cristen J. Willer aff015; Nima C. Emami aff020; Taylor B. Cavazos aff020; John S. Witte aff020; Agnieszka Szwajda aff024; aff007; ; David A. Hinds aff007; Norbert Hübner aff005; Stephan Weidinger aff003; Patrik KE Magnusson aff010; Eric Jorgenson aff025; Robert Karlsson aff010; Lavinia Paternoster aff012; Dorret I. Boomsma aff009; Catarina Almqvist aff010; Young-Ae Lee aff005; Gerard H. Koppelman aff027
Působiště autorů:
Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
aff001; University of Groningen, University Medical Center Groningen, Epidemiology, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands
aff002; Epidemiology, University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands
aff002; Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
aff003; Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
aff004; Max Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany
aff005; Clinic for Pediatric Allergy, Experimental and Clinical Research Center of Charité Universitätsmedizin Berlin and Max Delbrück Center, Berlin, Germany
aff006; 23andMe, Inc., Mountain View, California, United States of America
aff007; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America
aff008; Department Biological Psychology, Netherlands Twin Register, Vrije University, Amsterdam, The Netherlands
aff009; Department of Medical Epidemiology and Biostatistics and the Swedish Twin Registry, Karolinska Institutet, Stockholm, Sweden
aff010; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
aff011; MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom
aff012; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
aff013; Department of Thoracic Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
aff014; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, United States of America
aff015; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, United States of America
aff016; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America
aff017; The HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
aff018; Department of Dermatology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
aff019; Program in Biological and Medical Informatics, University of California, San Francisco, San Francisco, California, United States of America
aff020; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, United States of America
aff021; Institute for Human Genetics, University of California, San Francisco, San Francisco, California, United States of America
aff022; Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, United States of America
aff023; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
aff024; Division of Research, Kaiser Permanente Northern California, Oakland, California, United States of America
aff025; Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden
aff026; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027; University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD,
aff027
Vyšlo v časopise:
Age-of-onset information helps identify 76 genetic variants associated with allergic disease. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008725
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008725
Souhrn
Risk factors that contribute to inter-individual differences in the age-of-onset of allergic diseases are poorly understood. The aim of this study was to identify genetic risk variants associated with the age at which symptoms of allergic disease first develop, considering information from asthma, hay fever and eczema. Self-reported age-of-onset information was available for 117,130 genotyped individuals of European ancestry from the UK Biobank study. For each individual, we identified the earliest age at which asthma, hay fever and/or eczema was first diagnosed and performed a genome-wide association study (GWAS) of this combined age-of-onset phenotype. We identified 50 variants with a significant independent association (P<3x10-8) with age-of-onset. Forty-five variants had comparable effects on the onset of the three individual diseases and 38 were also associated with allergic disease case-control status in an independent study (n = 222,484). We observed a strong negative genetic correlation between age-of-onset and case-control status of allergic disease (rg = -0.63, P = 4.5x10-61), indicating that cases with early disease onset have a greater burden of allergy risk alleles than those with late disease onset. Subsequently, a multivariate GWAS of age-of-onset and case-control status identified a further 26 associations that were missed by the univariate analyses of age-of-onset or case-control status only. Collectively, of the 76 variants identified, 18 represent novel associations for allergic disease. We identified 81 likely target genes of the 76 associated variants based on information from expression quantitative trait loci (eQTL) and non-synonymous variants, of which we highlight ADAM15, FOSL2, TRIM8, BMPR2, CD200R1, PRKCQ, NOD2, SMAD4, ABCA7 and UBE2L3. Our results support the notion that early and late onset allergic disease have partly distinct genetic architectures, potentially explaining known differences in pathophysiology between individuals.
Klíčová slova:
Allergic diseases – Allergic rhinitis – Asthma – Eczema – Food allergies – Genetics of disease – Genome-wide association studies – Medical risk factors
Zdroje
1. Vicente C.T., Revez J.A. & Ferreira M.A.R. Lessons from ten years of genome-wide association studies of asthma. Clinical and Translational Immunology 6, e165 (2017). doi: 10.1038/cti.2017.54 29333270
2. Waage J., et al. Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis. Nat Genet. 2018 Aug;50(8):1072–1080. doi: 10.1038/s41588-018-0157-1 30013184
3. Bunyavanich S. et al. Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis. BMC Med Genomics 7, 48 (2014). doi: 10.1186/1755-8794-7-48 25085501
4. Andiappan A.K. et al. Genome-wide association study for atopy and allergic rhinitis in a Singapore Chinese population. PLoS One 6, e19719 (2011). doi: 10.1371/journal.pone.0019719 21625490
5. Weidinger S. et al. A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis. Hum Mol Genet 22, 4841–56 (2013). doi: 10.1093/hmg/ddt317 23886662
6. Esparza-Gordillo J. et al. A common variant on chromosome 11q13 is associated with atopic dermatitis. Nat Genet 41, 596–601 (2009). doi: 10.1038/ng.347 19349984
7. Sun L.D. et al. Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population. Nat Genet 43, 690–4 (2011). doi: 10.1038/ng.851 21666691
8. Hirota T. et al. Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nat Genet 44, 1222–6 (2012). doi: 10.1038/ng.2438 23042114
9. Baurecht H. et al. Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms. Am J Hum Genet 96, 104–20 (2015). doi: 10.1016/j.ajhg.2014.12.004 25574825
10. Schaarschmidt H. et al. A genome-wide association study reveals 2 new susceptibility loci for atopic dermatitis. J Allergy Clin Immunol 136, 802–6 (2015). doi: 10.1016/j.jaci.2015.01.047 25865352
11. Paternoster L. et al. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet 47, 1449–56 (2015). doi: 10.1038/ng.3424 26482879
12. Kim K.W. et al. Genome-wide association study of recalcitrant atopic dermatitis in Korean children. J Allergy Clin Immunol 136, 678–684 e4 (2015). doi: 10.1016/j.jaci.2015.03.030 25935106
13. Hong X. et al. Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children. Nat Commun 6, 6304 (2015). doi: 10.1038/ncomms7304 25710614
14. Martino D.J. et al. Genomewide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1. Clin Exp Allergy 47, 217–223 (2017). doi: 10.1111/cea.12863 27883235
15. Marenholz I. et al. Genome-wide association study identifies the SERPINB gene cluster as a susceptibility locus for food allergy. Nat Commun 8, 1056 (2017). doi: 10.1038/s41467-017-01220-0 29051540
16. Asai Y. et al. Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy. J Allergy Clin Immunol 141, 991–1001 (2018). doi: 10.1016/j.jaci.2017.09.015 29030101
17. Marenholz I. et al. Meta-analysis identifies seven susceptibility loci involved in the atopic march. Nat Commun 6, 8804 (2015). doi: 10.1038/ncomms9804 26542096
18. Ferreira M.A. et al. Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype. J Allergy Clin Immunol 133, 1564–71 (2014). doi: 10.1016/j.jaci.2013.10.030 24388013
19. Hinds D.A. et al. A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. Nat Genet 45, 907–11 (2013). doi: 10.1038/ng.2686 23817569
20. Wan Y.I. et al. A genome-wide association study to identify genetic determinants of atopy in subjects from the United Kingdom. J Allergy Clin Immunol 127, 223–31, 231 e1-3 (2011). doi: 10.1016/j.jaci.2010.10.006 21094521
21. Bønnelykke K. et al. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. Nat Genet. 2013 Aug;45(8):902–906. doi: 10.1038/ng.2694 23817571
22. Ferreira M.A. et al. Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology. Nat Genet 49, 1752–1757 (2017). doi: 10.1038/ng.3985 29083406
23. Thomsen SF, et al. Genetic influence on the age at onset of asthma: a twin study. J Allergy Clin Immunol. 2010 Sep;126(3):626–30. doi: 10.1016/j.jaci.2010.06.017 20673982
24. Moffatt MF, et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 2007 Jul 26;448(7152):470–3. doi: 10.1038/nature06014 17611496
25. Bouzigon E, et al. Effect of 17q21 variants and smoking exposure in early-onset asthma. N Engl J Med. 2008 Nov 6;359(19):1985–94. doi: 10.1056/NEJMoa0806604 18923164
26. Moffatt MF, et al. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med. 2010 Sep 23;363(13):1211–1221. doi: 10.1056/NEJMoa0906312 20860503
27. Halapi E, et al. A sequence variant on 17q21 is associated with age at onset and severity of asthma. Eur J Hum Genet. 2010 Aug;18(8):902–8 doi: 10.1038/ejhg.2010.38 20372189
28. Forno E. et al. Genome-wide association study of the age of onset of childhood asthma. J Allergy Clin Immunol 130, 83–90 e4 (2012). doi: 10.1016/j.jaci.2012.03.020 22560479
29. Sarnowski C. et al. Identification of a new locus at 16q12 associated with time to asthma onset. J Allergy Clin Immunol 138, 1071–1080 (2016). doi: 10.1016/j.jaci.2016.03.018 27130862
30. Bulik-Sullivan B.K. et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet (2015).
31. Demenais F, et al. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks. Nat Genet. 2018 Jan;50(1):42–53 doi: 10.1038/s41588-017-0014-7 29273806
32. Bulik-Sullivan B. et al. An atlas of genetic correlations across human diseases and traits. Nat Genet 47, 1236–41 (2015). doi: 10.1038/ng.3406 26414676
33. Ray D, Boehnke M.Methods for meta-analysis of multiple traits using GWAS summary statistics. Genet Epidemiol. 2018 Mar;42(2):134–145. doi: 10.1002/gepi.22105 29226385
34. Turley P. et al. Multi-trait analysis of genome-wide association summary statistics using MTAG. Nat Genet Nat Genet. 2018 Feb;50(2):229–237. doi: 10.1038/s41588-017-0009-4 29292387
35. Smith F.J. et al. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 38, 337–42 (2006). doi: 10.1038/ng1743 16444271
36. Cichonska A. et al. metaCCA: summary statistics-based multivariate meta-analysis of genome-wide association studies using canonical correlation analysis. Bioinformatics 32, 1981–9 (2016). doi: 10.1093/bioinformatics/btw052 27153689
37. Belsky D.W. et al. Polygenic risk and the development and course of asthma: an analysis of data from a four-decade longitudinal study. Lancet Respir Med 1, 453–61 (2013). doi: 10.1016/S2213-2600(13)70101-2 24429243
38. Ahmed S., Maratha A., Butt A.Q., Shevlin E. & Miggin S.M. TRIF-mediated TLR3 and TLR4 signaling is negatively regulated by ADAM15. J Immunol 190, 2217–28 (2013). doi: 10.4049/jimmunol.1201630 23365087
39. Fourie A.M., Coles F., Moreno V. & Karlsson L. Catalytic activity of ADAM8, ADAM15, and MDC-L (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23. J Biol Chem 278, 30469–77 (2003). doi: 10.1074/jbc.M213157200 12777399
40. Ubieta K. et al. Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription. J Exp Med 214, 2059–2071 (2017). doi: 10.1084/jem.20160514 28566276
41. Wurm S. et al. Terminal epidermal differentiation is regulated by the interaction of Fra-2/AP-1 with Ezh2 and ERK1/2. Genes Dev 29, 144–56 (2015). doi: 10.1101/gad.249748.114 25547114
42. Ciofani M. et al. A validated regulatory network for Th17 cell specification. Cell 151, 289–303 (2012). doi: 10.1016/j.cell.2012.09.016 23021777
43. Li Q. et al. Tripartite motif 8 (TRIM8) modulates TNFalpha- and IL-1beta-triggered NF-kappaB activation by targeting TAK1 for K63-linked polyubiquitination. Proc Natl Acad Sci U S A 108, 19341–6 (2011). doi: 10.1073/pnas.1110946108 22084099
44. Ye W. et al. TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking TRIF-TBK1 Interaction. J Immunol 199, 1856–1864 (2017). doi: 10.4049/jimmunol.1601647 28747347
45. Rosenzweig B.L. et al. Cloning and characterization of a human type II receptor for bone morphogenetic proteins. Proc Natl Acad Sci U S A 92, 7632–6 (1995). doi: 10.1073/pnas.92.17.7632 7644468
46. Rudarakanchana N. et al. Functional analysis of bone morphogenetic protein type II receptor mutations underlying primary pulmonary hypertension. Hum Mol Genet 11, 1517–25 (2002). doi: 10.1093/hmg/11.13.1517 12045205
47. Wright G.J. et al. Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function. Immunity 13, 233–42 (2000). doi: 10.1016/s1074-7613(00)00023-6 10981966
48. Hoek R.M. et al. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 290, 1768–71 (2000). doi: 10.1126/science.290.5497.1768 11099416
49. Cherwinski H.M. et al. The CD200 receptor is a novel and potent regulator of murine and human mast cell function. J Immunol 174, 1348–56 (2005). doi: 10.4049/jimmunol.174.3.1348 15661892
50. Jenmalm M.C., Cherwinski H., Bowman E.P., Phillips J.H. & Sedgwick J.D. Regulation of myeloid cell function through the CD200 receptor. J Immunol 176, 191–9 (2006). doi: 10.4049/jimmunol.176.1.191 16365410
51. Fallarino F. et al. Murine plasmacytoid dendritic cells initiate the immunosuppressive pathway of tryptophan catabolism in response to CD200 receptor engagement. J Immunol 173, 3748–54 (2004). doi: 10.4049/jimmunol.173.6.3748 15356121
52. Sen S. et al. SRC1 promotes Th17 differentiation by overriding Foxp3 suppression to stimulate RORgammat activity in a PKC-theta-dependent manner. Proc Natl Acad Sci U S A 115, E458–E467 (2018). doi: 10.1073/pnas.1717789115 29282318
53. Salek-Ardakani S., So T., Halteman B.S., Altman A. & Croft M. Differential regulation of Th2 and Th1 lung inflammatory responses by protein kinase C theta. J Immunol 173, 6440–7 (2004). doi: 10.4049/jimmunol.173.10.6440 15528385
54. Gupta S. et al. Differential requirement of PKC-theta in the development and function of natural regulatory T cells. Mol Immunol 46, 213–24 (2008). doi: 10.1016/j.molimm.2008.08.275 18842300
55. Madouri F. et al. Protein kinase Ctheta controls type 2 innate lymphoid cell and TH2 responses to house dust mite allergen. J Allergy Clin Immunol 139, 1650–1666 (2017). doi: 10.1016/j.jaci.2016.08.044 27746240
56. Girardin S.E. et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 278, 8869–72 (2003). doi: 10.1074/jbc.C200651200 12527755
57. Sabbah A. et al. Activation of innate immune antiviral responses by Nod2. Nat Immunol 10, 1073–80 (2009). doi: 10.1038/ni.1782 19701189
58. Maeda S. et al. Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science 307, 734–8 (2005). doi: 10.1126/science.1103685 15692052
59. Netea M.G. et al. NOD2 mediates anti-inflammatory signals induced by TLR2 ligands: implications for Crohn's disease. Eur J Immunol 34, 2052–9 (2004). doi: 10.1002/eji.200425229 15214053
60. Kobayashi K.S. et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307, 731–4 (2005). doi: 10.1126/science.1104911 15692051
61. Zhang Y., Feng X., We R. & Derynck R. Receptor-associated Mad homologues synergize as effectors of the TGF-beta response. Nature 383, 168–72 (1996). doi: 10.1038/383168a0 8774881
62. Kim B.G. et al. Smad4 signalling in T cells is required for suppression of gastrointestinal cancer. Nature 441, 1015–9 (2006). doi: 10.1038/nature04846 16791201
63. Hahn J.N., Falck V.G. & Jirik F.R. Smad4 deficiency in T cells leads to the Th17-associated development of premalignant gastroduodenal lesions in mice. J Clin Invest 121, 4030–42 (2011). doi: 10.1172/JCI45114 21881210
64. Zhang S. et al. Reversing SKI-SMAD4-mediated suppression is essential for TH17 cell differentiation. Nature 551, 105–109 (2017). doi: 10.1038/nature24283 29072299
65. Ebel M.E. & Kansas G.S. Functions of Smad Transcription Factors in TGF-beta1-Induced Selectin Ligand Expression on Murine CD4 Th Cells. J Immunol 197, 2627–34 (2016). doi: 10.4049/jimmunol.1600723 27543612
66. Wang A. et al. Cutting edge: Smad2 and Smad4 regulate TGF-beta-mediated Il9 gene expression via EZH2 displacement. J Immunol 191, 4908–12 (2013). doi: 10.4049/jimmunol.1300433 24108699
67. Abe-Dohmae S., Ueda K. & Yokoyama S. ABCA7, a molecule with unknown function. FEBS Lett 580, 1178–82 (2006). doi: 10.1016/j.febslet.2005.12.029 16376881
68. Jehle A.W. et al. ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages. J Cell Biol 174, 547–56 (2006). doi: 10.1083/jcb.200601030 16908670
69. Nowyhed H.N. et al. ATP Binding Cassette Transporter ABCA7 Regulates NKT Cell Development and Function by Controlling CD1d Expression and Lipid Raft Content. Sci Rep 7, 40273 (2017). doi: 10.1038/srep40273 28091533
70. Kielar D. et al. Adenosine triphosphate binding cassette (ABC) transporters are expressed and regulated during terminal keratinocyte differentiation: a potential role for ABCA7 in epidermal lipid reorganization. J Invest Dermatol 121, 465–74 (2003). doi: 10.1046/j.1523-1747.2003.12404.x 12925201
71. Bednash J.S. & Mallampalli R.K. Regulation of inflammasomes by ubiquitination. Cell Mol Immunol 13, 722–728 (2016). doi: 10.1038/cmi.2016.15 27063466
72. Fu B., Li S., Wang L., Berman M.A. & Dorf M.E. The ubiquitin conjugating enzyme UBE2L3 regulates TNFalpha-induced linear ubiquitination. Cell Res 24, 376–9 (2014). doi: 10.1038/cr.2013.133 24060851
73. Simmons A. et al. Nef-mediated lipid raft exclusion of UbcH7 inhibits Cbl activity in T cells to positively regulate signaling. Immunity 23, 621–34 (2005). doi: 10.1016/j.immuni.2005.11.003 16356860
74. Kathania M. et al. Ndfip1 regulates itch ligase activity and airway inflammation via UbcH7. J Immunol 194, 2160–7 (2015). doi: 10.4049/jimmunol.1402742 25632008
75. Eldridge M.J.G., Sanchez-Garrido J., Hoben G.F., Goddard P.J. & Shenoy A.R. The Atypical Ubiquitin E2 Conjugase UBE2L3 Is an Indirect Caspase-1 Target and Controls IL-1beta Secretion by Inflammasomes. Cell Rep 18, 1285–1297 (2017). doi: 10.1016/j.celrep.2017.01.015 28147281
76. Bycroft C, Freeman C, Petkova D, Band G, Elliott LT, Sharp K, Motyer A, Vukcevic D, Delaneau O, O'Connell J, Cortes A, Welsh S, Young A, Effingham M, McVean G, Leslie S, Allen N, Donnelly P, Marchini J. The UK Biobank resource with deep phenotyping and genomic data. Nature. 2018 Oct;562(7726):203–209 doi: 10.1038/s41586-018-0579-z 30305743
77. Loh P.R. et al. Efficient Bayesian mixed-model analysis increases association power in large cohorts. Nat Genet 47, 284–90 (2015). doi: 10.1038/ng.3190 25642633
78. Fadista J., Manning A.K., Florez J.C. & Groop L. The (in)famous GWAS P-value threshold revisited and updated for low-frequency variants. Eur J Hum Genet 24, 1202–5 (2016). doi: 10.1038/ejhg.2015.269 26733288
79. Yang J. et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat Genet 44, 369–75, S1-3 (2012). doi: 10.1038/ng.2213 22426310
80. Ferreira M.A. & Purcell S.M. A multivariate test of association. Bioinformatics 25, 132–3 (2009). doi: 10.1093/bioinformatics/btn563 19019849
81. O'Reilly P.F. et al. MultiPhen: joint model of multiple phenotypes can increase discovery in GWAS. PLoS One 7, e34861 (2012). doi: 10.1371/journal.pone.0034861 22567092
82. Genomes Project C. et al. An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56–65 (2012). doi: 10.1038/nature11632 23128226
83. Welter D. et al. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 42, D1001–6 (2014). doi: 10.1093/nar/gkt1229 24316577
84. Ferreira MAR et al. Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct. Am J Hum Genet. 2019 Apr 4;104(4):665–684. doi: 10.1016/j.ajhg.2019.02.022 30929738
85. Pierce B.L. et al. Mediation analysis demonstrates that trans-eQTLs are often explained by cis-mediation: a genome-wide analysis among 1,800 South Asians. PLoS Genet 10, e1004818 (2014). doi: 10.1371/journal.pgen.1004818 25474530
86. Davis J.R. et al. An Efficient Multiple-Testing Adjustment for eQTL Studies that Accounts for Linkage Disequilibrium between Variants. Am J Hum Genet 98, 216–24 (2016). doi: 10.1016/j.ajhg.2015.11.021 26749306
87. Lappalainen T. et al. Transcriptome and genome sequencing uncovers functional variation in humans. Nature 501, 506–11 (2013). doi: 10.1038/nature12531 24037378
88. Montgomery S.B. et al. Transcriptome genetics using second generation sequencing in a Caucasian population. Nature 464, 773–7 (2010). doi: 10.1038/nature08903 20220756
89. Chang C.C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015). doi: 10.1186/s13742-015-0047-8 25722852
90. Chang X. & Wang K. wANNOVAR: annotating genetic variants for personal genomes via the web. J Med Genet 49, 433–6 (2012). doi: 10.1136/jmedgenet-2012-100918 22717648
Článek vyšel v časopise
PLOS Genetics
2020 Číslo 6
- Antibiotika na nachlazení nezabírají! Jak můžeme zpomalit šíření rezistence?
- FDA varuje před selfmonitoringem cukru pomocí chytrých hodinek. Jak je to v Česku?
- Prof. Jan Škrha: Metformin je bezpečný, ale je třeba jej bezpečně užívat a léčbu kontrolovat
- Ibuprofen jako alternativa antibiotik při léčbě infekcí močových cest
- Jak a kdy u celiakie začíná reakce na lepek? Možnou odpověď poodkryla čerstvá kanadská studie
Nejčtenější v tomto čísle
- AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization
- Osteocalcin promotes bone mineralization but is not a hormone
- Super-resolution imaging of RAD51 and DMC1 in DNA repair foci reveals dynamic distribution patterns in meiotic prophase
- Steroid hormones regulate genome-wide epigenetic programming and gene transcription in human endometrial cells with marked aberrancies in endometriosis