Systems genetics analysis of genome-wide association study reveals novel associations between key biological processes and coronary artery disease

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 35, Issue 7, 2015, Pages 1712-1722

  Ghosh, Sujoy ^b   Vivar, Juan ^a   Nelson, Christopher P ^a   Willenborg, Christina ^a   Segrè, Ayellet V ^a   Mäkinen, Ville Petteri ^a   Nikpay, Majid ^a   Erdmann, Jeannette ^a   Blankenberg, Stefan ^a   O'Donnell, Christopher ^a   März, Winfried ^a   Laaksonen, Reijo ^a   Stewart, Alexandre F R ^a   Epstein, Stephen E ^a   Shah, Svati H ^a   Granger, Christopher B ^a   Hazen, Stanley L ^a   Kathiresan, Sekar ^a   Reilly, Muredach P ^a   Yang, Xia ^a   Quertermous, Thomas ^a   Samani, Nilesh J ^a   Schunkert, Heribert ^a   Assimes, Themistocles L ^c   McPherson, Ruth ^a   more..

^a UNIVERSITY OF OTTAWA HEART INSTITUTE   (Canada)

^b DUKE NUS MEDICAL SCHOOL   (Singapore)

^c STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

coronary artery disease; pathway analysis

Indexed keywords

NOTCH RECEPTOR; PLATELET DERIVED GROWTH FACTOR; SMAD PROTEIN; TRANSFORMING GROWTH FACTOR BETA;

ADULT; AGED; ARTICLE; CONTROLLED CLINICAL TRIAL (TOPIC); CONTROLLED STUDY; CORONARY ARTERY DISEASE; EXTRACELLULAR MATRIX; FOLLOW UP; GENE IDENTIFICATION; GENE REPLICATION; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC VARIABILITY; HUMAN; INNATE IMMUNITY; LIPID TRANSPORT; MAJOR CLINICAL STUDY; META ANALYSIS (TOPIC); PRIORITY JOURNAL; GENETICS; META ANALYSIS; METABOLISM;

CORONARY ARTERY DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS;

EID: 84933052819     PISSN: 10795642     EISSN: 15244636     Source Type: Journal    
DOI: 10.1161/ATVBAHA.115.305513     Document Type: Article

References (46)

1. Schunkert H, König IR, Kathiresan S, Cardiogenics; CARDIoGRAM Consortium Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet 2011 43 333 338. doi: 10.1038/ng.784
2. Deloukas P, Kanoni S, Willenborg C, Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet 2012 45 25 33
3. Dickson SP, Wang K, Krantz I, Hakonarson H, Goldstein DB., Rare variants create synthetic genome-wide associations. PLoS Biol 2010 8 e1000294. doi: 10.1371/journal.pbio.1000294
4. Cirulli ET, Goldstein DB., Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet 2010 11 415 425. doi: 10.1038/nrg2779
5. Visscher PM, Brown MA, McCarthy MI, Yang J., Five years of GWAS discovery. Am J Hum Genet 2012 90 7 24. doi: 10.1016/j.ajhg.2011.11.029
6. Yang J, Benyamin B, McEvoy BP, Gordon S, Henders AK, Nyholt DR, Madden PA, Heath AC, Martin NG, Montgomery GW, Goddard ME, Visscher PM., Common SNPs explain a large proportion of the heritability for human height. Nat Genet 2010 42 565 569. doi: 10.1038/ng.608
7. Stahl EA, Wegmann D, Trynka G, Diabetes Genetics Replication and Meta-analysis Consortium; Myocardial Infarction Genetics Consortium Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis. Nat Genet 2012 44 483 489. doi: 10.1038/ng.2232
8. Jia P, Wang L, Fanous AH, Pato CN, Edwards TL, Zhao Z, International Schizophrenia Consortium Network-assisted investigation of combined causal signals from genome-wide association studies in schizophrenia. PLoS Comput Biol 2012 8 e1002587. doi: 10.1371/journal.pcbi.1002587
9. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP., Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 2005 102 15545 15550. doi: 10.1073/pnas.0506580102
10. Wang K, Li M, Bucan M., Pathway-based approaches for analysis of genomewide association studies. Am J Hum Genet 2007 81 1278 1283. doi: 10.1086/522374
11. Wang K, Li M, Hakonarson H., Analysing biological pathways in genome-wide association studies. Nat Rev Genet 2010 11 843 854. doi: 10.1038/nrg2884
12. Wang L, Jia P, Wolfinger RD, Chen X, Zhao Z., Gene set analysis of genome-wide association studies: methodological issues and perspectives. Genomics 2011 98 1 8. doi: 10.1016/j.ygeno.2011.04.006
13. Segrè AV, DIAGRAM Consortium; MAGIC investigators Groop L, Mootha VK, Daly MJ, Altshuler D, DIAGRAM Consortium; MAGIC investigators Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits. PLoS Genet 2010 6 e1001058. doi: 10.1371/journal.pgen.1001058
14. Nam D, Kim J, Kim SY, Kim S., GSA-SNP: a general approach for gene set analysis of polymorphisms. Nucleic Acids Res 2010 38 web server issue W749 W754. doi: 10.1093/nar/gkq428
15. Zhang K, Cui S, Chang S, Zhang L, Wang J., i-GSEA4GWAS: a web server for identification of pathways/gene sets associated with traits by applying an improved gene set enrichment analysis to genome-wide association study. Nucleic Acids Res 2010 38 web server issue W90 W95. doi: 10.1093/nar/gkq324
16. Oti M, Brunner HG., The modular nature of genetic diseases. Clin Genet 2007 71 1 11. doi: 10.1111/j.1399-0004.2006.00708.x
17. Feldman I, Rzhetsky A, Vitkup D., Network properties of genes harboring inherited disease mutations. Proc Natl Acad Sci USA 2008 105 4323 4328. doi: 10.1073/pnas.0701722105
18. Baranzini SE, Galwey NW, Wang J, Khankhanian P, Lindberg R, Pelletier D, Wu W, Uitdehaag BM, Kappos L, Polman CH, Matthews PM, Hauser SL, Gibson RA, Oksenberg JR, Barnes MR, GeneMSA Consortium Pathway and network-based analysis of genome-wide association studies in multiple sclerosis. Hum Mol Genet 2009 18 2078 2090. doi: 10.1093/hmg/ddp120
19. Lu C, Latourelle J, O'Connor GT, Dupuis J, Kolaczyk ED., Network-guided sparse regression modeling for detection of gene-by-gene interactions. Bioinformatics 2013 29 1241 1249. doi: 10.1093/bioinformatics/btt139
20. Wang L, Matsushita T, Madireddy L, Mousavi P, Baranzini SE., PINBPA: cytoscape app for network analysis of GWAS data. Bioinformatics 2015 31 262 264. doi: 10.1093/bioinformatics/btu644
21. Matthews L, Gopinath G, Gillespie M, Reactome knowledgebase of human biological pathways and processes. Nucleic Acids Res 2009 37 database issue D619 D622. doi: 10.1093/nar/gkn863
22. Yu H, Kim PM, Sprecher E, Trifonov V, Gerstein M., The importance of bottlenecks in protein networks: correlation with gene essentiality and expression dynamics. PLoS Comput Biol 2007 3 e59. doi: 10.1371/journal.pcbi.0030059
23. Toma I, McCaffrey TA., Transforming growth factor-β and atherosclerosis: interwoven atherogenic and atheroprotective aspects. Cell Tissue Res 2012 347 155 175. doi: 10.1007/s00441-011-1189-3
24. Raines EW., PDGF and cardiovascular disease. Cytokine Growth Factor Rev 2004 15 237 254. doi: 10.1016/j.cytogfr.2004.03.004
25. Katsuda S, Kaji T., Atherosclerosis and extracellular matrix. J Atheroscler Thromb 2003 10 267 274
26. Schmidt EF, Strittmatter SM., The CRMP family of proteins and their role in Sema3A signaling. Adv Exp Med Biol 2007 600 1 11. doi: 10.1007/978-0-387-70956-7-1
27. van Gils JM, Derby MC, Fernandes LR, The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques. Nat Immunol 2012 13 136 143. doi: 10.1038/ni.2205
28. Oksala N, Pärssinen J, Seppälä I, Raitoharju E, Kholova I, Ivana K, Hernesniemi J, Lyytikäinen LP, Levula M, Mäkelä KM, Sioris T, Kähönen M, Laaksonen R, Hytönen V, Lehtimäki T., Association of neuroimmune guidance cue netrin-1 and its chemorepulsive receptor UNC5B with atherosclerotic plaque expression signatures and stability in human(s): Tampere Vascular Study (TVS). Circ Cardiovasc Genet 2013 6 579 587. doi: 10.1161/CIRCGENETICS.113.000141
29. Wanschel A, Seibert T, Hewing B, Ramkhelawon B, Ray TD, van Gils JM, Rayner KJ, Feig JE, O'Brien ER, Fisher EA, Moore KJ., Neuroimmune guidance cue Semaphorin 3E is expressed in atherosclerotic plaques and regulates macrophage retention. Arterioscler Thromb Vasc Biol 2013 33 886 893. doi: 10.1161/ATVBAHA.112.300941
30. van Gils JM, Ramkhelawon B, Fernandes L, Stewart MC, Guo L, Seibert T, Menezes GB, Cara DC, Chow C, Kinane TB, Fisher EA, Balcells M, Alvarez-Leite J, Lacy-Hulbert A, Moore KJ., Endothelial expression of guidance cues in vessel wall homeostasis dysregulation under proatherosclerotic conditions. Arterioscler Thromb Vasc Biol 2013 33 911 919. doi: 10.1161/ATVBAHA.112.301155
31. Hansson GK, Hermansson A., The immune system in atherosclerosis. Nat Immunol 2011 12 204 212. doi: 10.1038/ni.2001
32. Serini G, Valdembri D, Zanivan S, Morterra G, Burkhardt C, Caccavari F, Zammataro L, Primo L, Tamagnone L, Logan M, Tessier-Lavigne M, Taniguchi M, Püschel AW, Bussolino F., Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function. Nature 2003 424 391 397. doi: 10.1038/nature01784
33. Lanahan A, Zhang X, Fantin A, Zhuang Z, Rivera-Molina F, Speichinger K, Prahst C, Zhang J, Wang Y, Davis G, Toomre D, Ruhrberg C, Simons M., The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis. Dev Cell 2013 25 156 168. doi: 10.1016/j.devcel.2013.03.019
34. Ji JD, Park-Min KH, Ivashkiv LB., Expression and function of semaphorin 3A and its receptors in human monocyte-derived macrophages. Hum Immunol 2009 70 211 217. doi: 10.1016/j.humimm.2009.01.026
35. Bauer RC, Stylianou IM, Rader DJ., Functional validation of new pathways in lipoprotein metabolism identified by human genetics. Curr Opin Lipidol 2011 22 123 128. doi: 10.1097/MOL.0b013e32834469b3
36. Musunuru K, Strong A, Frank-Kamenetsky M, From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 2010 466 714 719. doi: 10.1038/nature09266
37. Kjolby M, Andersen OM, Breiderhoff T, Fjorback AW, Pedersen KM, Madsen P, Jansen P, Heeren J, Willnow TE, Nykjaer A., Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export. Cell Metab 2010 12 213 223. doi: 10.1016/j.cmet.2010.08.006
38. Burkhardt R, Toh SA, Lagor WR, Birkeland A, Levin M, Li X, Robblee M, Fedorov VD, Yamamoto M, Satoh T, Akira S, Kathiresan S, Breslow JL, Rader DJ., Trib1 is a lipid-and myocardial infarction-associated gene that regulates hepatic lipogenesis and VLDL production in mice. J Clin Invest 2010 120 4410 4414. doi: 10.1172/JCI44213
39. Papassotiropoulos A, Gerhards C, Heck A, Human genome-guided identification of memory-modulating drugs. Proc Natl Acad Sci USA 2013 110 E4369 E4374. doi: 10.1073/pnas.1314478110
40. Khatri P, Sirota M, Butte AJ., Ten years of pathway analysis: current approaches and outstanding challenges. PLoS Comput Biol 2012 8 e1002375. doi: 10.1371/journal.pcbi.1002375
41. Erbilgin A, Civelek M, Romanoski CE, Pan C, Hagopian R, Berliner JA, Lusis AJ., Identification of CAD candidate genes in GWAS loci and their expression in vascular cells. J Lipid Res 2013 54 1894 1905. doi: 10.1194/jlr.M037085
42. Mäkinen VP, Civelek M, Meng Q, Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Consortium Integrative genomics reveals novel molecular pathways and gene networks for coronary artery disease. PLoS Genet 2014 10 e1004502. doi: 10.1371/journal.pgen.1004502
43. Wang K, Zhang H, Kugathasan S, Diverse genome-wide association studies associate the IL12/IL23 pathway with Crohn Disease. Am J Hum Genet 2009 84 399 405. doi: 10.1016/j.ajhg.2009.01.026
44. Holmans P, Moskvina V, Jones L, International Parkinson's Disease Genomics Consortium A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease. Hum Mol Genet 2013 22 1039 1049. doi: 10.1093/hmg/dds492
45. Rozenblatt-Rosen O, Deo RC, Padi M, Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 2012 487 491 495. doi: 10.1038/nature11288
46. Olsen C, Fleming K, Prendergast N, Rubio R, Emmert-Streib F, Bontempi G, Haibe-Kains B, Quackenbush J., Inference and validation of predictive gene networks from biomedical literature and gene expression data. Genomics 2014 103 329 336. doi: 10.1016/j.ygeno.2014.03.004