Gene-based analysis of regulatory variants identifies 4 putative novel asthma risk genes related to nucleotide synthesis and signaling

Journal of Allergy and Clinical Immunology

Volumn 139, Issue 4, 2017, Pages 1148-1157

  Ferreira, Manuel A R ^a   Jansen, Rick ^b   Willemsen, Gonneke ^c   Penninx, Brenda ^b   Bain, Lisa M ^a   Vicente, Cristina T ^a   Revez, Joana A ^a   Matheson, Melanie C ^d   Hui, Jennie ^e,f,h   Tung, Joyce Y ⁱ   Baltic, Svetlana ^j   Le Souëf, Peter ^k   Montgomery, Grant W ^a   Martin, Nicholas G ^a   Robertson, Colin F ^l   James, Alan ^g,h,m   Thompson, Philip J ^g,j   Boomsma, Dorret I ^c   Hopper, John L ^d   Hinds, David A ⁱ   Werder, Rhiannon B ⁿ   Phipps, Simon ⁿ   more..

^a QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^b VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^c VU UNIVERSITY AMSTERDAM   (Netherlands)

^d UNIVERSITY OF MELBOURNE   (Australia)

^e PATHWEST LABORATORY MEDICINE   (Australia)

^f UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^g UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^h SIR CHARLES GAIRDNER HOSPITAL   (Australia)

ⁱ Harry Perkins Institute of Medical Research ^*  (United States)

^j UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^k PRINCESS MARGARET HOSPITAL FOR CHILDREN   (Australia)

^l MURDOCH CHILDREN'S RESEARCH INSTITUTE   (Australia)

^m Department of Pulmonary Physiology West Australian Sleep Disorders Research Institute   (Australia)

ⁿ UNIVERSITY OF QUEENSLAND   (Australia)

more..

Author keywords

AOAH; CLK3; EUGENE; expression quantitative trait locus; Inflammation; obesity; P2Y13; P2Y14; predisposition; PrediXcan; transcriptome; TWAS; UDP glucose; VEGAS; ZNF707

Indexed keywords

ADENOSINE DIPHOSPHATE; ANTIGEN PEPTIDE TRANSPORTER 2; GROWTH FACTOR RECEPTOR BOUND PROTEIN 7; HLA DQA1 ANTIGEN; HLA DQB1 ANTIGEN; HLA DRB1 ANTIGEN; INTERLEUKIN 33; NUCLEAR RECEPTOR NR1D1; SMAD3 PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING 1; THYMIC STROMAL LYMPHOPOIETIN; TOLL LIKE RECEPTOR 1; TRANSPORTER ASSOCIATED WITH ANTIGEN PROCESSING 1; URIDINE DIPHOSPHATE GLUCOSE; URIDINE DIPHOSPHATE SUGAR; DAPIT PROTEIN, HUMAN; NUCLEOTIDE; P2RY13 PROTEIN, HUMAN; P2RY13 PROTEIN, MOUSE; P2RY14 PROTEIN, HUMAN; P2RY14 PROTEIN, MOUSE; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; PURINERGIC P2 RECEPTOR; PURINERGIC P2Y RECEPTOR;

ACO2 GENE; ANIMAL EXPERIMENT; ANIMAL MODEL; AOAH GENE; ARTICLE; ASTHMA; B4GALT3 GENE; CELL INFILTRATION; CISD3 GENE; CLEC16A GENE; CLK3 GENE; CONTROLLED STUDY; CYTOKINE RELEASE; DYNC1H1 GENE; FLOW CYTOMETRY; GENE; GENE EXPRESSION; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC VARIABILITY; GSDMB GENE; HAPLOTYPE; HCP5 GENE; HEREDITY; HIBADH GENE; HLA DRB6 GENE; HSPA1B GENE; IKZF3 GENE; IL18R1 GENE; IL18RAP GENE; IL1RL2 GENE; LIMS1 GENE; LTA GENE; MED24 GENE; MICB GENE; MOUSE; NEU1 GENE; NONHUMAN; NUCLEOTIDE METABOLISM; ORMDL3 GENE; P2RY12 GENE; P2RY13 GENE; P2RY14 GENE; PGAP3 GENE; PRIORITY JOURNAL; PTCSC3 GENE; QUANTITATIVE TRAIT LOCUS; REEP3 GENE; SAFB GENE; SLC44A4 GENE; STARD3 GENE; TINF2 GENE; TOP2A GENE; UPREGULATION; USMG5 GENE; ZNF707 GENE; ZPBP2 GENE; ANIMAL; BIOSYNTHESIS; C57BL MOUSE; GENETIC PREDISPOSITION; GENETIC VARIATION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; HUMAN; PROCEDURES; SOFTWARE;

ANIMALS; ASTHMA; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MICE; MICE, INBRED C57BL; MITOCHONDRIAL PROTON-TRANSLOCATING ATPASES; NUCLEOTIDES; QUANTITATIVE TRAIT LOCI; RECEPTORS, PURINERGIC P2; RECEPTORS, PURINERGIC P2Y; SOFTWARE;

EID: 84995807142     PISSN: 00916749     EISSN: 10976825     Source Type: Journal    
DOI: 10.1016/j.jaci.2016.07.017     Document Type: Article

References (59)

1. 1 Ferreira, M.A., Matheson, M.C., Duffy, D.L., Marks, G.B., Hui, J., Le Souef, P., et al. Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet 378 (2011), 1006–1014.
2. 2 Moffatt, M.F., Kabesch, M., Liang, L., Dixon, A.L., Strachan, D., Heath, S., et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448 (2007), 470–473.
3. 3 Vicente, C.T., Edwards, S.L., Hillman, K.M., Kaufmann, S., Mitchell, H., Bain, L., et al. Long-range modulation of PAG1 expression by 8q21 allergy risk variants. Am J Hum Genet 97 (2015), 329–336.
4. 4 Okada, Y., Wu, D., Trynka, G., Raj, T., Terao, C., Ikari, K., et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506 (2014), 376–381.
5. 5 Nelson, M.R., Tipney, H., Painter, J.L., Shen, J., Nicoletti, P., Shen, Y., et al. The support of human genetic evidence for approved drug indications. Nat Genet 47 (2015), 856–860.
6. 6 Ferreira, M.A., Improving the power to detect risk variants for allergic disease by defining case-control status based on both asthma and hay fever. Twin Res Hum Genet 17 (2014), 505–511.
7. 7 Bonnelykke, K., Sleiman, P., Nielsen, K., Kreiner-Moller, E., Mercader, J.M., Belgrave, D., et al. A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. Nat Genet 46 (2014), 51–55.
8. 8 Galesloot, T.E., van Steen, K., Kiemeney, L.A., Janss, L.L., Vermeulen, S.H., A comparison of multivariate genome-wide association methods. PLoS One, 9, 2014, e95923.
9. 9 Liu, J.Z., McRae, A.F., Nyholt, D.R., Medland, S.E., Wray, N.R., Brown, K.M., et al. A versatile gene-based test for genome-wide association studies. Am J Hum Genet 87 (2010), 139–145.
10. 10 Li, M.X., Gui, H.S., Kwan, J.S., Sham, P.C., GATES: a rapid and powerful gene-based association test using extended Simes procedure. Am J Hum Genet 88 (2011), 283–293.
11. 11 Nicolae, D.L., Gamazon, E., Zhang, W., Duan, S., Dolan, M.E., Cox, N.J., Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS. PLoS Genet, 6, 2010, e1000888.
12. 12 Gamazon, E.R., Wheeler, H.E., Shah, K.P., Mozaffari, S.V., Aquino-Michaels, K., Carroll, R.J., et al. A gene-based association method for mapping traits using reference transcriptome data. Nat Genet 47 (2015), 1091–1098.
13. 13 Gusev, A., Ko, A., Shi, H., Bhatia, G., Chung, W., Penninx, B.W., et al. Integrative approaches for large-scale transcriptome-wide association studies. Nat Genet 48 (2016), 245–252.
14. 14 Ferreira, M.A., Matheson, M.C., Tang, C.S., Granell, R., Ang, W., Hui, J., et al. Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype. J Allergy Clin Immunol 133 (2014), 1564–1571.
15. 15 Moffatt, M.F., Gut, I.G., Demenais, F., Strachan, D.P., Bouzigon, E., Heath, S., et al. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 363 (2010), 1211–1221.
16. 16 Ullah, M.A., Revez, J.A., Loh, Z., Simpson, J., Zhang, V., Bain, L., et al. Allergen-induced IL-6 trans-signaling activates gammadelta T cells to promote type 2 and type 17 airway inflammation. J Allergy Clin Immunol 136 (2015), 1065–1073.
17. 17 Davidson, S., Kaiko, G., Loh, Z., Lalwani, A., Zhang, V., Spann, K., et al. Plasmacytoid dendritic cells promote host defense against acute pneumovirus infection via the TLR7-MyD88-dependent signaling pathway. J Immunol 186 (2011), 5938–5948.
18. 18 Torgerson, D.G., Ampleford, E.J., Chiu, G.Y., Gauderman, W.J., Gignoux, C.R., Graves, P.E., et al. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet 43 (2011), 887–892.
19. 19 Zeller, T., Wild, P., Szymczak, S., Rotival, M., Schillert, A., Castagne, R., et al. Genetics and beyond—the transcriptome of human monocytes and disease susceptibility. PLoS One, 5, 2010, e10693.
20. 20 Westra, H.J., Peters, M.J., Esko, T., Yaghootkar, H., Schurmann, C., Kettunen, J., et al. Systematic identification of trans eQTLs as putative drivers of known disease associations. Nat Genet 45 (2013), 1238–1243.
21. 21 Kim, S., Becker, J., Bechheim, M., Kaiser, V., Noursadeghi, M., Fricker, N., et al. Characterizing the genetic basis of innate immune response in TLR4-activated human monocytes. Nat Commun, 5, 2014, 5236.
22. 22 Pierce, B.L., Tong, L., Chen, L.S., Rahaman, R., Argos, M., Jasmine, F., 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, 2014, e1004818.
23. 23 Berndt, S.I., Gustafsson, S., Magi, R., Ganna, A., Wheeler, E., Feitosa, M.F., et al. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. Nat Genet 45 (2013), 501–512.
24. 24 Soranzo, N., Spector, T.D., Mangino, M., Kuhnel, B., Rendon, A., Teumer, A., et al. A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. Nat Genet 41 (2009), 1182–1190.
25. 25 Kuga, W., Tsuchihara, K., Ogura, T., Kanehara, S., Saito, M., Suzuki, A., et al. Nuclear localization of SNARK; its impact on gene expression. Biochem Biophys Res Commun 377 (2008), 1062–1066.
26. 26 Lo, N.W., Shaper, J.H., Pevsner, J., Shaper, N.L., The expanding beta 4-galactosyltransferase gene family: messages from the databanks. Glycobiology 8 (1998), 517–526.
27. 27 Gao, Z.G., Ding, Y., Jacobson, K.A., P2Y(13) receptor is responsible for ADP-mediated degranulation in RBL-2H3 rat mast cells. Pharmacol Res 62 (2010), 500–505.
28. 28 Muller, T., Bayer, H., Myrtek, D., Ferrari, D., Sorichter, S., Ziegenhagen, M.W., et al. The P2Y14 receptor of airway epithelial cells: coupling to intracellular Ca2+ and IL-8 secretion. Am J Respir Cell Mol Biol 33 (2005), 601–609.
29. 29 Guo, S., Sato, T., Shirane, K., Furukawa, K., Galactosylation of N-linked oligosaccharides by human beta-1,4-galactosyltransferases I, II, III, IV, V, and VI expressed in Sf-9 cells. Glycobiology 11 (2001), 813–820.
30. 30 Liao, W.C., Liu, C.H., Chen, C.H., Hsu, W.M., Liao, Y.Y., Chang, H.M., et al. beta-1,4-Galactosyltransferase III suppresses extravillous trophoblast invasion through modifying beta1-integrin glycosylation. Placenta 36 (2015), 357–364.
31. 31 Suzuki, K., Okuno, T., Yamamoto, M., Pasterkamp, R.J., Takegahara, N., Takamatsu, H., et al. Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin. Nature 446 (2007), 680–684.
32. 32 Lazarowski, E.R., Quantification of extracellular UDP-galactose. Anal Biochem 396 (2010), 23–29.
33. 33 Meyer, B., Wittig, I., Trifilieff, E., Karas, M., Schagger, H., Identification of two proteins associated with mammalian ATP synthase. Mol Cell Proteomics 6 (2007), 1690–1699.
34. 34 Ohsakaya, S., Fujikawa, M., Hisabori, T., Yoshida, M., Knockdown of DAPIT (diabetes-associated protein in insulin-sensitive tissue) results in loss of ATP synthase in mitochondria. J Biol Chem 286 (2011), 20292–20296.
35. 35 Ledderose, C., Bao, Y., Lidicky, M., Zipperle, J., Li, L., Strasser, K., et al. Mitochondria are gate-keepers of T cell function by producing the ATP that drives purinergic signaling. J Biol Chem 289 (2014), 25936–25945.
36. 36 Yip, L., Woehrle, T., Corriden, R., Hirsh, M., Chen, Y., Inoue, Y., et al. Autocrine regulation of T-cell activation by ATP release and P2X7 receptors. FASEB J 23 (2009), 1685–1693.
37. 37 Vantourout, P., Radojkovic, C., Lichtenstein, L., Pons, V., Champagne, E., Martinez, L.O., Ecto-F(1)-ATPase: a moonlighting protein complex and an unexpected apoA-I receptor. World J Gastroenterol 16 (2010), 5925–5935.
38. 38 Jacquet, S., Malaval, C., Martinez, L.O., Sak, K., Rolland, C., Perez, C., et al. The nucleotide receptor P2Y13 is a key regulator of hepatic high-density lipoprotein (HDL) endocytosis. Cell Mol Life Sci 62 (2005), 2508–2515.
39. 39 Scotet, E., Martinez, L.O., Grant, E., Barbaras, R., Jeno, P., Guiraud, M., et al. Tumor recognition following Vgamma9Vdelta2 T cell receptor interactions with a surface F1-ATPase-related structure and apolipoprotein A-I. Immunity 22 (2005), 71–80.
40. 40 Communi, D., Gonzalez, N.S., Detheux, M., Brezillon, S., Lannoy, V., Parmentier, M., et al. Identification of a novel human ADP receptor coupled to G(i). J Biol Chem 276 (2001), 41479–41485.
41. 41 Zhang, F.L., Luo, L., Gustafson, E., Palmer, K., Qiao, X., Fan, X., et al. P2Y(13): identification and characterization of a novel Galphai-coupled ADP receptor from human and mouse. J Pharmacol Exp Ther 301 (2002), 705–713.
42. 42 Inoue, K., Hosoi, J., Denda, M., Extracellular ATP has stimulatory effects on the expression and release of IL-6 via purinergic receptors in normal human epidermal keratinocytes. J Invest Dermatol 127 (2007), 362–371.
43. 43 Kreda, S.M., Seminario-Vidal, L., van Heusden, C.A., O'Neal, W., Jones, L., Boucher, R.C., et al. Receptor-promoted exocytosis of airway epithelial mucin granules containing a spectrum of adenine nucleotides. J Physiol 588 (2010), 2255–2267.
44. 44 la Sala, A., Ferrari, D., Corinti, S., Cavani, A., Di Virgilio, F., Girolomoni, G., Extracellular ATP induces a distorted maturation of dendritic cells and inhibits their capacity to initiate Th1 responses. J Immunol 166 (2001), 1611–1617.
45. 45 Idzko, M., Dichmann, S., Ferrari, D., Di Virgilio, F., la Sala, A., Girolomoni, G., et al. Nucleotides induce chemotaxis and actin polymerization in immature but not mature human dendritic cells via activation of pertussis toxin-sensitive P2y receptors. Blood 100 (2002), 925–932.
46. 46 Chambers, J.K., Macdonald, L.E., Sarau, H.M., Ames, R.S., Freeman, K., Foley, J.J., et al. A G protein-coupled receptor for UDP-glucose. J Biol Chem 275 (2000), 10767–10771.
47. 47 Harden, T.K., Sesma, J.I., Fricks, I.P., Lazarowski, E.R., Signalling and pharmacological properties of the P2Y receptor. Acta Physiol (Oxf) 199 (2010), 149–160.
48. 48 Lazarowski, E.R., Shea, D.A., Boucher, R.C., Harden, T.K., Release of cellular UDP-glucose as a potential extracellular signaling molecule. Mol Pharmacol 63 (2003), 1190–1197.
49. 49 Okada, S.F., Zhang, L., Kreda, S.M., Abdullah, L.H., Davis, C.W., Pickles, R.J., et al. Coupled nucleotide and mucin hypersecretion from goblet-cell metaplastic human airway epithelium. Am J Respir Cell Mol Biol 45 (2011), 253–260.
50. 50 Kreda, S.M., Okada, S.F., van Heusden, C.A., O'Neal, W., Gabriel, S., Abdullah, L., et al. Coordinated release of nucleotides and mucin from human airway epithelial Calu-3 cells. J Physiol 584 (2007), 245–259.
51. 51 Shin, A., Toy, T., Rothenfusser, S., Robson, N., Vorac, J., Dauer, M., et al. P2Y receptor signaling regulates phenotype and IFN-alpha secretion of human plasmacytoid dendritic cells. Blood 111 (2008), 3062–3069.
52. 52 Sesma, J.I., Kreda, S.M., Steinckwich-Besancon, N., Dang, H., Garcia-Mata, R., Harden, T.K., et al. The UDP-sugar-sensing P2Y(14) receptor promotes Rho-mediated signaling and chemotaxis in human neutrophils. Am J Physiol Cell Physiol 303 (2012), C490–C498.
53. 53 Gao, Z.G., Ding, Y., Jacobson, K.A., UDP-glucose acting at P2Y14 receptors is a mediator of mast cell degranulation. Biochem Pharmacol 79 (2010), 873–879.
54. 54 Arase, T., Uchida, H., Kajitani, T., Ono, M., Tamaki, K., Oda, H., et al. The UDP-glucose receptor P2RY14 triggers innate mucosal immunity in the female reproductive tract by inducing IL-8. J Immunol 182 (2009), 7074–7084.
55. 55 Jokela, T.A., Karna, R., Makkonen, K.M., Laitinen, J.T., Tammi, R.H., Tammi, M.I., Extracellular UDP-glucose activates P2Y14 receptor and induces signal transducer and activator of transcription 3 (STAT3) Tyr705 phosphorylation and binding to hyaluronan synthase 2 (HAS2) promoter, stimulating hyaluronan synthesis of keratinocytes. J Biol Chem 289 (2014), 18569–18581.
56. 56 Barrett, M.O., Sesma, J.I., Ball, C.B., Jayasekara, P.S., Jacobson, K.A., Lazarowski, E.R., et al. A selective high-affinity antagonist of the P2Y14 receptor inhibits UDP-glucose-stimulated chemotaxis of human neutrophils. Mol Pharmacol 84 (2013), 41–49.
57. 57 Xu, J., Morinaga, H., Oh, D., Li, P., Chen, A., Talukdar, S., et al. GPR105 ablation prevents inflammation and improves insulin sensitivity in mice with diet-induced obesity. J Immunol 189 (2012), 1992–1999.
58. 58 Kouzaki, H., Iijima, K., Kobayashi, T., O'Grady, S.M., Kita, H., The danger signal, extracellular ATP, is a sensor for an airborne allergen and triggers IL-33 release and innate Th2-type responses. J Immunol 186 (2011), 4375–4387.
59. 59 Moussion, C., Ortega, N., Girard, J.P., The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel ‘alarmin’?. PLoS One, 3, 2008, e3331.