Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology

Nature Genetics

Volumn 49, Issue 12, 2017, Pages 1752-1757

  Ferreira, Manuel A ^a   Vonk, Judith M ^b   Baurecht, Hansjörg ^c   Marenholz, Ingo ^d,e   Tian, Chao ^f   Hoffman, Joshua D ^g   Helmer, Quinta ^h   Tillander, Annika ⁱ   Ullemar, Vilhelmina ⁱ   Van Dongen, Jenny ^h   Lu, Yi ⁱ   Rüschendorf, Franz ^d   Esparza Gordillo, Jorge ^d,e,ab   Medway, Chris W ^j   Mountjoy, Edward ^j   Burrows, Kimberley ^j   Hummel, Oliver ^d   Grosche, Sarah ^d,e   Brumpton, Ben M ^j,k,l   Witte, John S ^g   Hottenga, Jouke Jan ^h   Willemsen, Gonneke ^h   Zheng, Jie ^j   Rodríguez, Elke ^c   Hotze, Melanie ^c   Franke, Andre ^m   Revez, Joana A ^a   Beesley, Jonathan ^a   Matheson, Melanie C ⁿ   Dharmage, Shyamali C ⁿ   Bain, Lisa M ^a   Fritsche, Lars G ^k   Gabrielsen, Maiken E ^k   Balliu, Brunilda ^o   Nielsen, Jonas B ^o,p   Zhou, Wei ^p   Hveem, Kristian ^k   Langhammer, Arnulf ^k   Holmen, Oddgeir L ^k   Løset, Mari ^k,l   Abecasis, Goncalo R ^k,q   Willer, Cristen J ^k,p,q   Arnold, Andreas ^r   Homuth, Georg ^r   Schmidt, Carsten O ^r   Thompson, Philip J ^s   Martin, Nicholas G ^a   Duffy, David L ^a   Novak, Natalija ^t   Schulz, Holger ^u   Karrasch, Stefan ^v   Gieger, Christian ^u,w   Strauch, Konstantin ^u   Melles, Ronald B ^u   Hinds, David A ^x   Hübner, Norbert ^f   Weidinger, Stephan ^d   Magnusson, Patrik K E ^c   Jansen, Rick ⁱ   Jorgenson, Eric ^y   Lee, Young Ae ^x   Boomsma, Dorret I ^d,e   Almqvist, Catarina ^h   Karlsson, Robert ^i,z   Koppelman, Gerard H ^i,aa   Paternoster, Lavinia ^j   more..

^a QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^b UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^c UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

^d MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^e CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^f Research 23 and Me   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

^h VU UNIVERSITY AMSTERDAM   (Netherlands)

ⁱ KAROLINSKA INSTITUTE   (Sweden)

^j UNIVERSITY OF BRISTOL   (United Kingdom)

^k NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

^l TRONDHEIM UNIVERSITY HOSPITAL   (Norway)

^m UNIVERSITY OF KIEL   (Germany)

ⁿ UNIVERSITY OF MELBOURNE   (Australia)

^o STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^p UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^q UNIVERSITY OF MICHIGAN   (United States)

^r UNIVERSITY MEDICINE GREIFSWALD   (Germany)

^s UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^t UNIVERSITY HOSPITAL BONN   (Germany)

^u INSTITUTE OF EPIDEMIOLOGY   (Germany)

^v German Center for Lung Research (DZL CPC M)   (Germany)

^w LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^x DIVISION OF RESEARCH   (United States)

^y VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^z KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^aa UNIVERSITY OF GRONINGEN   (Netherlands)

^ab GLAXOSMITHKLINE   (United Kingdom)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CD86 ANTIGEN; CHEMOKINE RECEPTOR CCR7; DNA;

ALLERGIC DISEASE; ARTICLE; ASTHMA; BIOLOGICAL PHENOMENA AND FUNCTIONS CONCERNING THE ENTIRE ORGANISM; BIOLOGY; CPG ISLAND; ECZEMA; GENE EXPRESSION; GENE FREQUENCY; GENETIC RISK; GENETIC TRANSCRIPTION; GENETIC VARIABILITY; HEREDITY; HERITABILITY; HUMAN; IMMUNITY; MAJOR CLINICAL STUDY; PATHOPHYSIOLOGY; PHENOTYPE; POLLEN ALLERGY; PRIORITY JOURNAL; RISK FACTOR; GENETIC PREDISPOSITION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; HYPERSENSITIVITY; META ANALYSIS; PROCEDURES; SINGLE NUCLEOTIDE POLYMORPHISM;

ASTHMA; ECZEMA; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; HYPERSENSITIVITY; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; RHINITIS, ALLERGIC, SEASONAL; RISK FACTORS;

EID: 85035776645     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.3985     Document Type: Article

References (50)

1. Pinart, M., et al. Comorbidity of eczema, rhinitis, asthma in IgE-sensitised, non-IgE-sensitised children in MeDALL: A population-based cohort study. Lancet Respir. Med. 2, 131-140 (2014).
2. Thomsen, S.F., et al. Findings on the atopic triad from a Danish twin registry. Int. J. Tuberc. Lung Dis. 10, 1268-1272 (2006).
3. van Beijsterveldt, C.E. , Boomsma, D.I. Genetics of parentally reported asthma, eczema, rhinitis in 5-yr-old twins. Eur. Respir. J. 29, 516-521 (2007).
4. Loh, P.R., et al. Contrasting genetic architectures of schizophrenia, other complex diseases using fast variance-components analysis. Nat. Genet. 47, 1385-1392 (2015).
5. Yang, J., et al. Conditional, joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat. Genet. 44, 369-375, S1-S3 (2012).
6. Ferreira, M.A. Improving the power to detect risk variants for allergic disease by defining case-control status based on both asthma, hay fever. Twin Res. Hum. Genet. 17, 505-511 (2014).
7. Bulik-Sullivan, B.K., et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat. Genet. 47, 291-295 (2015).
8. GTEx Consortium. The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans. Science 348, 648-660 (2015).
9. Wells, A., et al. The anatomical distribution of genetic associations. Nucleic Acids Res. 43, 10804-10820 (2015).
10. Finucane, H.K., et al. Partitioning heritability by functional annotation using genomewide association summary statistics. Nat. Genet. 47, 1228-1235 (2015).
11. Farh, K.K., et al. Genetic, epigenetic fine mapping of causal autoimmune disease variants. Nature 518, 337-343 (2015).
12. Fehrmann, R.S., et al. Gene expression analysis identifies global gene dosage sensitivity in cancer. Nat. Genet. 47, 115-125 (2015).
13. Thomsen, S.F., Kyvik, K.O. , Backer, V. Etiological relationships in atopy: A review of twin studies. Twin Res. Hum. Genet. 11, 112-120 (2008).
14. Sanseau, P., et al. Use of genome-wide association studies for drug repositioning. Nat. Biotechnol. 30, 317-320 (2012).
15. Bonder, M.J., et al. Disease variants alter transcription factor levels, methylation of their binding sites. Nat. Genet. 49, 131-138 (2017).
16. Joehanes, R., et al. Epigenetic signatures of cigarette smoking. Circ Cardiovasc Genet 9, 436-447 (2016).
17. Lev, S., et al. Identification of a novel family of targets of PYK2 related to Drosophila retinal degeneration B (rdgB) protein. Mol. Cell. Biol. 19, 2278-2288 (1999).
18. Yan, S.R. , Novak, M.J. integrin-dependent phosphorylation of protein-tyrosine kinase Pyk2 stimulated by tumor necrosis factor and fMLP in human neutrophils adherent to fibrinogen. FEBS Lett. 451, 33-38 (1999).
19. Kamen, L.A., Schlessinger, J. , Lowell, C.A. Pyk2 is required for neutrophil degranulation, host defense responses to bacterial infection. J. Immunol. 186, 1656-1665 (2011).
20. Willer, C.J., Li, Y. , Abecasis, G.R. METAL: Fast, efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190-2191 (2010).
21. Fadista, J., Manning, A.K., Florez, J.C. , Groop, L. The (in)famous GWAS P-value threshold revisited, updated for low-frequency variants. Eur. J. Hum. Genet. 24, 1202-1205 (2016).
22. Gough, H., et al. Allergic multimorbidity of asthma, rhinitis, eczema over 20 years in the German birth cohort MAS. Pediatr. Allergy Immunol. 26, 431-437 (2015).
23. Mortz, C.G., Andersen, K.E., Dellgren, C., Barington, T. , Bindslev-Jensen, C. Atopic dermatitis from adolescence to adulthood in the TOACS cohort: Prevalence, persistence, comorbidities. Allergy 70, 836-845 (2015).
24. 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).
25. Dharmage, S.C., et al. Atopic dermatitis, the atopic march revisited. Allergy 69, 17-27 (2014).
26. Chang, X. , Wang, K. wANNOVAR: Annotating genetic variants for personal genomes via the web. J. Med. Genet. 49, 433-436 (2012).
27. 1000 Genomes Project Consortium. An integrated map of genetic variation from 1, 092 human genomes. Nature 491, 56-65 (2012).
28. Rebhan, M., Chalifa-Caspi, V., Prilusky, J. , Lancet, D. GeneCards: Integrating information about genes, proteins, diseases. Trends Genet. 13, 163 (1997).
29. 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, 216-224 (2016).
30. Montgomery, S.B., et al. Transcriptome genetics using second generation sequencing in a Caucasian population. Nature 464, 773-777 (2010).
31. Lappalainen, T., et al. Transcriptome, genome sequencing uncovers functional variation in humans. Nature 501, 506-511 (2013).
32. Westra, H.J., et al. Systematic identification of trans eQTLs as putative drivers of known disease associations. Nat. Genet. 45, 1238-1243 (2013).
33. Chun, S., et al. Limited statistical evidence for shared genetic effects of eQTLs, autoimmune-disease-associated loci in three major immune-cell types. Nat. Genet. 49, 600-605 (2017).
34. Sanyal, A., Lajoie, B.R., Jain, G. , Dekker, J. The long-range interaction landscape of gene promoters. Nature 489, 109-113 (2012).
35. Mifsud, B., et al. Mapping long-range promoter contacts in human cells with highresolution capture Hi-C. Nat. Genet. 47, 598-606 (2015).
36. Li, G., et al. Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell 148, 84-98 (2012).
37. Rao, S.S., et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665-1680 (2014).
38. Corradin, O., et al. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits. Genome Res. 24, 1-13 (2014).
39. Hnisz, D., et al. Super-enhancers in the control of cell identity, disease. Cell 155, 934-947 (2013).
40. He, B., Chen, C., Teng, L. , Tan, K. Global view of enhancer-promoter interactome in human cells. Proc. Natl. Acad. Sci. USA 111, E2191-E2199 (2014).
41. Andersson, R., et al. An atlas of active enhancers across human cell types, tissues. Nature 507, 455-461 (2014).
42. Welter, D., et al. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res. 42, D1001-D1006 (2014).
43. Astle, W.J., et al. The allelic landscape of human blood cell trait variation, links to common complex disease. Cell 167, 1415-1429.e19 (2016).
44. Zheng, J., et al. LD Hub: A centralized database, web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability, genetic correlation analysis. Bioinformatics 33, 272-279 (2017).
45. Fairfax, B.P., et al. Genetics of gene expression in primary immune cells identifies cell type-specific master regulators, roles of HLA alleles. Nat. Genet. 44, 502-510 (2012).
46. Fairfax, B.P., et al. Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression. Science 343, 1246949 (2014).
47. Fu, J., et al. Unraveling the regulatory mechanisms underlying tissue-dependent genetic variation of gene expression. PLoS Genet. 8, e1002431 (2012).
48. Zhernakova, D.V., et al. Identification of context-dependent expression quantitative trait loci in whole blood. Nat. Genet. 49, 139-145 (2017).
49. Willemsen, G., et al. The Netherlands Twin Register biobank: A resource for genetic epidemiological studies. Twin Res. Hum. Genet. 13, 231-245 (2010).
50. Tsai, P.C., et al. DNA methylation changes in the IGF1R gene in birth weight discordant adult monozygotic twins. Twin Res. Hum. Genet. 18, 635-646 (2015).