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Genetic Causes of Cardiac Disease pp 359–379Cite as

Systems Medicine as a Transforming Tool for Cardiovascular Genetics

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Part of the book series: Cardiac and Vascular Biology ((Abbreviated title: Card. vasc. biol.,volume 7))

Abstract

Cardiovascular diseases represent one of the most important causes of morbidity and mortality worldwide. The pathogenesis of cardiovascular disease is complex and remains elusive. Remarkable progress in deciphering the molecular mechanisms of cardiovascular disease has been achieved in different fields of research, ranging from basic-experimental research to molecular epidemiology to clinical research. Each of these isolated fields have successfully improved the pathophysiological understanding in cardiovascular disease. Within the last years, systems medicine has emerged to study the complex genetic, molecular, and physiological interactions leading to cardiovascular diseases by integrating and combining multilevel data sets from different research fields.

This chapter provides an overview of the current understanding of systems medicine and the computational and epidemiological tools applied. First, applications of systems medicine in cardiovascular research are described and challenges and opportunities that arise with systems medicine as a promising tool for cardiovascular genetics are discussed.

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References

  1. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, De Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P. Heart disease and stroke statistics-2017 update: A report from the American Heart Association. Circulation. 2017;135:e146–603.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rebhan M. Towards a systems approach for chronic diseases, based on health state modeling. F1000Res. 2017;6:309.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Barabasi AL, Oltvai ZN. Network biology: understanding the cell’s functional organization. Nat Rev Genet. 2004;5:101–13.

    Article  CAS  PubMed  Google Scholar 

  4. Kitano H. Computational systems biology. Nature. 2002;420:206–10.

    Article  CAS  PubMed  Google Scholar 

  5. Adam G, Delbruck M. Reduction of dimensionality in biological diffusion processes. San Francisco: W.H. Freeman & Company; 1968.

    Google Scholar 

  6. Hopfield JJ. Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc Natl Acad Sci U S A. 1974;71:4135–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Luria SE, Delbruck M. Mutations of bacteria from virus sensitivity to virus resistance. Genetics. 1943;28:491–511.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Auer PL, Stitziel NO. Genetic association studies in cardiovascular diseases: Do we have enough power? Trends Cardiovasc Med. 2017;27:397–404.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Howson JMM, Zhao W, Barnes DR, Ho WK, Young R, Paul DS, Waite LL, Freitag DF, Fauman EB, Salfati EL, Sun BB, Eicher JD, Johnson AD, Sheu WHH, Nielsen SF, Lin WY, Surendran P, Malarstig A, Wilk JB, Tybjaerg-Hansen A, Rasmussen KL, Kamstrup PR, Deloukas P, Erdmann J, Kathiresan S, Samani NJ, Schunkert H, Watkins H, Do R, Rader DJ, Johnson JA, Hazen SL, Quyyumi AA, Spertus JA, Pepine CJ, Franceschini N, Justice A, Reiner AP, Buyske S, Hindorff LA, Carty CL, North KE, Kooperberg C, Boerwinkle E, Young K, Graff M, Peters U, Absher D, Hsiung CA, Lee WJ, Taylor KD, Chen YH, Lee IT, Guo X, Chung RH, Hung YJ, Rotter JI, Juang JJ, Quertermous T, Wang TD, Rasheed A, Frossard P, Alam DS, Majumder AAS, Di Angelantonio E, Chowdhury R, Chen YI, Nordestgaard BG, Assimes TL, Danesh J, Butterworth AS, Saleheen D. Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms. Nat Genet. 2017;49:1113–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Nelson CP, Goel A, Butterworth AS, Kanoni S, Webb TR, Marouli E, Zeng L, Ntalla I, Lai FY, Hopewell JC, Giannakopoulou O, Jiang T, Hamby SE, Di Angelantonio E, Assimes TL, Bottinger EP, Chambers JC, Clarke R, Palmer CNA, Cubbon RM, Ellinor P, Ermel R, Evangelou E, Franks PW, Grace C, Gu D, Hingorani AD, Howson JMM, Ingelsson E, Kastrati A, Kessler T, Kyriakou T, Lehtimaki T, Lu X, Lu Y, Marz W, McPherson R, Metspalu A, Pujades-Rodriguez M, Ruusalepp A, Schadt EE, Schmidt AF, Sweeting MJ, Zalloua PA, Alghalayini K, Keavney BD, Kooner JS, Loos RJF, Patel RS, Rutter MK, Tomaszewski M, Tzoulaki I, Zeggini E, Erdmann J, Dedoussis G, Bjorkegren JLM, Schunkert H, Farrall M, Danesh J, Samani NJ, Watkins H, Deloukas P. Association analyses based on false discovery rate implicate new loci for coronary artery disease. Nat Genet. 2017;49:1385–91.

    Article  CAS  PubMed  Google Scholar 

  11. Nikpay M, Goel A, Won HH, Hall LM, Willenborg C, Kanoni S, Saleheen D, Kyriakou T, Nelson CP, Hopewell JC, Webb TR, Zeng L, Dehghan A, Alver M, Armasu SM, Auro K, Bjonnes A, Chasman DI, Chen S, Ford I, Franceschini N, Gieger C, Grace C, Gustafsson S, Huang J, Hwang SJ, Kim YK, Kleber ME, Lau KW, Lu X, Lu Y, Lyytikainen LP, Mihailov E, Morrison AC, Pervjakova N, Qu L, Rose LM, Salfati E, Saxena R, Scholz M, Smith AV, Tikkanen E, Uitterlinden A, Yang X, Zhang W, Zhao W, De Andrade M, De Vries PS, Van Zuydam NR, Anand SS, Bertram L, Beutner F, Dedoussis G, Frossard P, Gauguier D, Goodall AH, Gottesman O, Haber M, Han BG, Jalilzadeh S, Kessler T, Konig IR, Lannfelt L, Lieb W, Lind L, Lindgren CM, Lokki ML, Magnusson PK, Mallick NH, Mehra N, Meitinger T, Memon FU, Morris AP, Nieminen MS, Pedersen NL, Peters A, Rallidis LS, Rasheed A, Samuel M, Shah SH, Sinisalo J, Stirrups KE, Trompet S, Wang L, Zaman KS, Ardissino D, Boerwinkle E, Borecki IB, Bottinger EP, Buring JE, Chambers JC, Collins R, Cupples LA, Danesh J, Demuth I, Elosua R, Epstein SE, Esko T, Feitosa MF, Franco OH, et al. A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet. 2015;47:1121–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Erdmann J, Stark K, Esslinger UB, Rumpf PM, Koesling D, De Wit C, Kaiser FJ, Braunholz D, Medack A, Fischer M, Zimmermann ME, Tennstedt S, Graf E, Eck S, Aherrahrou Z, Nahrstaedt J, Willenborg C, Bruse P, Braenne I, Nothen MM, Hofmann P, Braund PS, Mergia E, Reinhard W, Burgdorf C, Schreiber S, Balmforth AJ, Hall AS, Bertram L, Steinhagen-Thiessen E, Li SC, Marz W, Reilly M, Kathiresan S, McPherson R, Walter U, Ott J, Samani NJ, Strom TM, Meitinger T, Hengstenberg C, Schunkert H. Dysfunctional nitric oxide signalling increases risk of myocardial infarction. Nature. 2013;504:432–6.

    Article  CAS  PubMed  Google Scholar 

  13. Wolkenhauer O, Auffray C, Jaster R, Steinhoff G, Dammann O. The road from systems biology to systems medicine. Pediatr Res. 2013;73:502–7.

    Article  PubMed  Google Scholar 

  14. Fischer T, Brothers KB, Erdmann P, Langanke M. Clinical decision-making and secondary findings in systems medicine. BMC Med Ethics. 2016;17:32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Barabasi AL, Albert R. Emergence of scaling in random networks. Science. 1999;286:509–12.

    Article  CAS  PubMed  Google Scholar 

  16. Watts DJ, Strogatz SH. Collective dynamics of ‘small-world’ networks. Nature. 1998;393:440–2.

    Article  CAS  PubMed  Google Scholar 

  17. Strogatz SH. Exploring complex networks. Nature. 2001;410:268–76.

    Article  CAS  PubMed  Google Scholar 

  18. Rajalingam K, Schreck R, Rapp UR, Albert S. Ras oncogenes and their downstream targets. Biochim Biophys Acta. 2007;1773:1177–95.

    Article  CAS  PubMed  Google Scholar 

  19. Hu JX, Thomas CE, Brunak S. Network biology concepts in complex disease comorbidities. Nat Rev Genet. 2016;17:615–29.

    Article  CAS  PubMed  Google Scholar 

  20. Chipman KC, Singh AK. Predicting genetic interactions with random walks on biological networks. BMC Bioinform. 2009;10:17.

    Article  CAS  Google Scholar 

  21. Bersanelli M, Mosca E, Remondini D, Castellani G, Milanesi L. Network diffusion-based analysis of high-throughput data for the detection of differentially enriched modules. Sci Rep. 2016;6:34841.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Vandin F, Upfal E, Raphael BJ. Algorithms for detecting significantly mutated pathways in cancer. J Comput Biol. 2011;18:507–22.

    Article  CAS  PubMed  Google Scholar 

  23. Network CGAR. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499:43–9.

    Article  CAS  Google Scholar 

  24. Mosca E, Bersanelli M, Gnocchi M, Moscatelli M, Castellani G, Milanesi L, Mezzelani A. Network diffusion-based prioritization of autism risk genes identifies significantly connected gene modules. Front Genet. 2017;8:129.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Stark C, Breitkreutz BJ, Reguly T, Boucher L, Breitkreutz A, Tyers M. BioGRID: a general repository for interaction datasets. Nucleic Acids Res. 2006;34:D535–9.

    Article  CAS  PubMed  Google Scholar 

  26. Bader GD, Donaldson I, Wolting C, Ouellette BF, Pawson T, Hogue CW. Bind – The biomolecular interaction network database. Nucleic Acids Res. 2001;29:242–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Xenarios I, Rice DW, Salwinski L, Baron MK, Marcotte EM, Eisenberg D. DIP: the database of interacting proteins. Nucleic Acids Res. 2000;28:289–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zanzoni A, Montecchi-Palazzi L, Quondam M, Ausiello G, Helmer-Citterich M, Cesareni G. MINT: a Molecular INTeraction database. FEBS Lett. 2002;513:135–40.

    Article  CAS  PubMed  Google Scholar 

  29. Hermjakob H, Montecchi-Palazzi L, Lewington C, Mudali S, Kerrien S, Orchard S, Vingron M, Roechert B, Roepstorff P, Valencia A, Margalit H, Armstrong J, Bairoch A, Cesareni G, Sherman D, Apweiler R. IntAct: an open source molecular interaction database. Nucleic Acids Res. 2004;32:D452–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Peri S, Navarro JD, Amanchy R, Kristiansen TZ, Jonnalagadda CK, Surendranath V, Niranjan V, Muthusamy B, Gandhi TK, Gronborg M, Ibarrola N, Deshpande N, Shanker K, Shivashankar HN, Rashmi BP, Ramya MA, Zhao Z, Chandrika KN, Padma N, Harsha HC, Yatish AJ, Kavitha MP, Menezes M, Choudhury DR, Suresh S, Ghosh N, Saravana R, Chandran S, Krishna S, Joy M, Anand SK, Madavan V, Joseph A, Wong GW, Schiemann WP, Constantinescu SN, Huang L, Khosravi-Far R, Steen H, Tewari M, Ghaffari S, Blobe GC, Dang CV, Garcia JG, Pevsner J, Jensen ON, Roepstorff P, Deshpande KS, Chinnaiyan AM, Hamosh A, Chakravarti A, Pandey A. Development of human protein reference database as an initial platform for approaching systems biology in humans. Genome Res. 2003;13:2363–71.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, Von Mering C. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43:D447–52.

    Article  CAS  PubMed  Google Scholar 

  32. Wang X, Gulbahce N, Yu H. Network-based methods for human disease gene prediction. Brief Funct Genomics. 2011;10:280–93.

    Article  CAS  PubMed  Google Scholar 

  33. Barabasi AL, Gulbahce N, Loscalzo J. Network medicine: a network-based approach to human disease. Nat Rev Genet. 2011;12:56–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lan A, Smoly IY, Rapaport G, Lindquist S, Fraenkel E, Yeger-Lotem E. ResponseNet: revealing signaling and regulatory networks linking genetic and transcriptomic screening data. Nucleic Acids Res. 2011;39:W424–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hofree M, Shen JP, Carter H, Gross A, Ideker T. Network-based stratification of tumor mutations. Nat Methods. 2013;10:1108–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhang B, Horvath S. A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol. 2005;4:Article 17.

    Article  Google Scholar 

  37. Liu J, Jing L, Tu X. Weighted gene co-expression network analysis identifies specific modules and hub genes related to coronary artery disease. BMC Cardiovasc Disord. 2016;16:54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Kwong LN, Costello JC, Liu H, Jiang S, Helms TL, Langsdorf AE, Jakubosky D, Genovese G, Muller FL, Jeong JH, Bender RP, Chu GC, Flaherty KT, Wargo JA, Collins JJ, Chin L. Oncogenic NRAS signaling differentially regulates survival and proliferation in melanoma. Nat Med. 2012;18:1503–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. 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 U S A. 2005;102:15545–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Herwig R, Hardt C, Lienhard M, Kamburov A. Analyzing and interpreting genome data at the network level with ConsensusPathDB. Nat Protoc. 2016;11:1889–907.

    Article  CAS  PubMed  Google Scholar 

  41. Kamburov A, Stelzl U, Lehrach H, Herwig R. The ConsensusPathDB interaction database: 2013 update. Nucleic Acids Res. 2013;41:D793–800.

    Article  CAS  PubMed  Google Scholar 

  42. Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28:27–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Croft D, O’kelly G, Wu G, Haw R, Gillespie M, Matthews L, Caudy M, Garapati P, Gopinath G, Jassal B, Jupe S, Kalatskaya I, Mahajan S, May B, Ndegwa N, Schmidt E, Shamovsky V, Yung C, Birney E, Hermjakob H, D'eustachio P, Stein L. Reactome: a database of reactions, pathways and biological processes. Nucleic Acids Res. 2011;39:D691–7.

    Article  CAS  PubMed  Google Scholar 

  44. Ashburner M, Ball CA, Blake JA, BOTSTEIN D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000;25:25–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Carithers LJ, Moore HM. The Genotype-Tissue Expression (GTEx) Project. Biopreserv Biobank. 2015;13:307–8.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Thul PJ, Lindskog C. The human protein atlas: A spatial map of the human proteome. Protein Sci. 2018;27(1):233–44.

    Article  CAS  PubMed  Google Scholar 

  47. Haase T, Bornigen D, Muller C, Zeller T. Systems medicine as an emerging tool for cardiovascular genetics. Front Cardiovasc Med. 2016;3:27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Song JW, Chung KC. Observational studies: cohort and case-control studies. Plast Reconstr Surg. 2010;126:2234–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Chen G, Levy D. Contributions of the Framingham Heart Study to the Epidemiology of Coronary Heart Disease. JAMA Cardiol. 2016;1:825–30.

    Article  PubMed  Google Scholar 

  50. Long MT, Fox CS. The Framingham Heart Study--67 years of discovery in metabolic disease. Nat Rev Endocrinol. 2016;12:177–83.

    Article  CAS  PubMed  Google Scholar 

  51. Investigators TA. The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators. Am J Epidemiol. 1989;129:687–702.

    Article  Google Scholar 

  52. Koch B, Schaper C, Ittermann T, Volzke H, Felix SB, Ewert R, Glaser S. Reference values for lung function testing in adults--results from the study of health in Pomerania (SHIP). Dtsch Med Wochenschr. 2009;134:2327–32.

    Article  CAS  PubMed  Google Scholar 

  53. Lowel H, Lewis M, Hormann A, Keil U. Case finding, data quality aspects and comparability of myocardial infarction registers: results of a south German register study. J Clin Epidemiol. 1991;44:249–60.

    Article  CAS  PubMed  Google Scholar 

  54. Wild PS, Zeller T, Beutel M, Blettner M, Dugi KA, Lackner KJ, Pfeiffer N, Munzel T, Blankenberg S. The Gutenberg Health Study. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2012;55:824–9.

    Article  CAS  PubMed  Google Scholar 

  55. Zeller T, Hughes M, Tuovinen T, Schillert A, Conrads-Frank A, Ruijter H, Schnabel RB, Kee F, Salomaa V, Siebert U, Thorand B, Ziegler A, Breek H, Pasterkamp G, Kuulasmaa K, Koenig W, Blankenberg S. BiomarCaRE: rationale and design of the European BiomarCaRE project including 300,000 participants from 13 European countries. Eur J Epidemiol. 2014;29:777–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mayrhofer MT, Holub P, Wutte A, Litton JE. BBMRI-ERIC: the novel gateway to biobanks. From humans to humans. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2016;59:379–84.

    Article  PubMed  Google Scholar 

  57. Simeon-Dubach D, Zeisberger SM, Hoerstrup SP. Quality assurance in biobanking for pre-clinical research. Transfus Med Hemother. 2016;43:353–7.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Rotival M, Zeller T, Wild PS, Maouche S, Szymczak S, Schillert A, Castagne R, Deiseroth A, Proust C, Brocheton J, Godefroy T, Perret C, Germain M, Eleftheriadis M, Sinning CR, Schnabel RB, Lubos E, Lackner KJ, Rossmann H, Munzel T, Rendon A, Erdmann J, Deloukas P, Hengstenberg C, Diemert P, Montalescot G, Ouwehand WH, Samani NJ, Schunkert H, Tregouet DA, Ziegler A, Goodall AH, Cambien F, Tiret L, Blankenberg S. Integrating genome-wide genetic variations and monocyte expression data reveals trans-regulated gene modules in humans. PLoS Genet. 2011;7:e1002367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kessler T, Wobst J, Wolf B, Eckhold J, Vilne B, Hollstein R, Von Ameln S, Dang TA, Sager HB, Moritz Rumpf P, Aherrahrou R, Kastrati A, Bjorkegren JLM, Erdmann J, Lusis AJ, Civelek M, Kaiser FJ, Schunkert H. Functional characterization of the GUCY1A3 coronary artery disease risk locus. Circulation. 2017;136:476–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Huan T, Esko T, Peters MJ, Pilling LC, Schramm K, Schurmann C, Chen BH, Liu C, Joehanes R, Johnson AD, Yao C, Ying SX, Courchesne P, Milani L, Raghavachari N, Wang R, Liu P, Reinmaa E, Dehghan A, Hofman A, Uitterlinden AG, Hernandez DG, Bandinelli S, Singleton A, Melzer D, Metspalu A, Carstensen M, Grallert H, Herder C, Meitinger T, Peters A, Roden M, Waldenberger M, Dorr M, Felix SB, Zeller T, Vasan R, O'donnell CJ, Munson PJ, Yang X, Prokisch H, Volker U, Van Meurs JB, Ferrucci L, Levy D. A meta-analysis of gene expression signatures of blood pressure and hypertension. PLoS Genet. 2015a;11:e1005035.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Huan T, Meng Q, Saleh MA, Norlander AE, Joehanes R, Zhu J, Chen BH, Zhang B, Johnson AD, Ying S, Courchesne P, Raghavachari N, Wang R, Liu P, O’donnell CJ, Vasan R, Munson PJ, Madhur MS, Harrison DG, Yang X, Levy D. Integrative network analysis reveals molecular mechanisms of blood pressure regulation. Mol Syst Biol. 2015b;11:799.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Saleh MA, McMaster WG, Wu J, Norlander AE, Funt SA, Thabet SR, Kirabo A, Xiao L, Chen W, Itani HA, Michell D, Huan T, Zhang Y, Takaki S, Titze J, Levy D, Harrison DG, Madhur MS. Lymphocyte adaptor protein Lnk deficiency exacerbates hypertension and end-organ inflammation. J Clin Invest. 2015;125:1189–202.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Zeller T, Schurmann C, Schramm K, Muller C, Kwon S, Wild PS, Teumer A, Herrington D, Schillert A, Iacoviello L, Kratzer A, Jagodzinski A, Karakas M, Ding J, Neumann JT, Kuulasmaa K, Gieger C, Kacprowski T, Schnabel RB, Roden M, Wahl S, Rotter JI, Ojeda F, Carstensen-Kirberg M, Tregouet DA, Dorr M, Meitinger T, Lackner KJ, Wolf P, Felix SB, Landmesser U, Costanzo S, Ziegler A, Liu Y, Volker U, Palmas W, Prokisch H, Guo X, Herder C, Blankenberg S, Homuth G. Transcriptome-wide analysis identifies novel associations with blood pressure. Hypertension. 2017;70:743–50.

    Article  CAS  PubMed  Google Scholar 

  64. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell. 2012;148:1258–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Jie Z, Xia H, Zhong SL, Feng Q, Li S, Liang S, Zhong H, Liu Z, Gao Y, Zhao H, Zhang D, Su Z, Fang Z, Lan Z, Li J, Xiao L, Li R, Li X, Li F, Ren H, Huang Y, Peng Y, Li G, Wen B, Dong B, Chen JY, Geng QS, Zhang ZW, Yang H, Wang J, Zhang X, Madsen L, Brix S, Ning G, Xu X, Liu X, Hou Y, Jia H, He K, Kristiansen K. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun. 2017;8:845.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Gilbert JA, Quinn RA, Debelius J, Xu ZZ, Morton J, Garg N, Jansson JK, Dorrestein PC, Knight R. Microbiome-wide association studies link dynamic microbial consortia to disease. Nature. 2016;535:94–103.

    Article  CAS  PubMed  Google Scholar 

  67. Ahn AC, Tewari M, Poon CS, Phillips RS. The limits of reductionism in medicine: could systems biology offer an alternative? PLoS Med. 2006;3:e208.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Gijzen H. Development: Big data for a sustainable future. Nature. 2013;502:38.

    Article  CAS  PubMed  Google Scholar 

  69. Eisenstein M. Big data: The power of petabytes. Nature. 2015;527:S2–4.

    Article  CAS  PubMed  Google Scholar 

  70. Lowes M, Kleiss M, Lueck R, Detken S, Koenig A, Nietert M, Beissbarth T, Stanek K, Langer C, Ghadimi M, Conradi LC, Homayounfar K. The utilization of multidisciplinary tumor boards (MDT) in clinical routine: results of a health care research study focusing on patients with metastasized colorectal cancer. Int J Color Dis. 2017;32(10):1463–9.

    Article  Google Scholar 

  71. Ginsburg GS, Willard HF. Genomic and personalized medicine: foundations and applications. Transl Res. 2009;154:277–87.

    Article  PubMed  Google Scholar 

  72. Mirnezami R, Nicholson J, Darzi A. Preparing for precision medicine. N Engl J Med. 2012;366:489–91.

    Article  PubMed  Google Scholar 

  73. Harris JR, Burton P, Knoppers BM, Lindpaintner K, Bledsoe M, Brookes AJ, Budin-Ljosne I, Chisholm R, Cox D, Deschenes M, Fortier I, Hainaut P, Hewitt R, Kaye J, Litton JE, Metspalu A, Ollier B, Palmer LJ, Palotie A, Pasterk M, Perola M, Riegman PH, Van Ommen GJ, Yuille M, Zatloukal K. Toward a roadmap in global biobanking for health. Eur J Hum Genet. 2012;20:1105–11.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Walport M, Brest P. Sharing research data to improve public health. Lancet. 2011;377:537–9.

    Article  PubMed  Google Scholar 

  75. Muilu J, Peltonen L, Litton JE. The federated database--a basis for biobank-based post-genome studies, integrating phenome and genome data from 600,000 twin pairs in Europe. Eur J Hum Genet. 2007;15:718–23.

    Article  CAS  PubMed  Google Scholar 

  76. Doiron D, Burton P, Marcon Y, Gaye A, Wolffenbuttel BHR, Perola M, Stolk RP, Foco L, Minelli C, Waldenberger M, Holle R, Kvaloy K, Hillege HL, Tasse AM, Ferretti V, Fortier I. Data harmonization and federated analysis of population-based studies: the BioSHaRE project. Emerg Themes Epidemiol. 2013;10:12.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Brazma A, Hingamp P, Quackenbush J, Sherlock G, Spellman P, Stoeckert C, Aach J, Ansorge W, Ball CA, Causton HC, Gaasterland T, Glenisson P, Holstege FC, Kim IF, Markowitz V, Matese JC, Parkinson H, Robinson A, Sarkans U, Schulze-Kremer S, Stewart J, Taylor R, Vilo J, Vingron M. Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet. 2001;29:365–71.

    Article  CAS  PubMed  Google Scholar 

  78. Lappalainen I, Almeida-King J, Kumanduri V, Senf A, Spalding JD, Ur-Rehman S, Saunders G, Kandasamy J, Caccamo M, Leinonen R, Vaughan B, Laurent T, Rowland F, Marin-Garcia P, Barker J, Jokinen P, Torres AC, De Argila JR, Llobet OM, Medina I, Puy MS, Alberich M, De La Torre S, Navarro A, Paschall J, Flicek P. The European Genome-phenome Archive of human data consented for biomedical research. Nat Genet. 2015;47:692–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Caulfield T, Murdoch B. Genes, cells, and biobanks: Yes, there’s still a consent problem. PLoS Biol. 2017;15:e2002654.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Grabe HJ, Assel H, Bahls T, Dorr M, Endlich K, Endlich N, Erdmann P, Ewert R, Felix SB, Fiene B, Fischer T, Flessa S, Friedrich N, Gadebusch-Bondio M, Salazar MG, Hammer E, Haring R, Havemann C, Hecker M, Hoffmann W, Holtfreter B, Kacprowski T, Klein K, Kocher T, Kock H, Krafczyk J, Kuhn J, Langanke M, Lendeckel U, Lerch MM, Lieb W, Lorbeer R, Mayerle J, Meissner K, Zu Schwabedissen HM, Nauck M, Ott K, Rathmann W, Rettig R, Richardt C, Salje K, Schminke U, Schulz A, Schwab M, Siegmund W, Stracke S, Suhre K, Ueffing M, Ungerer S, Volker U, Volzke H, Wallaschofski H, Werner V, Zygmunt MT, Kroemer HK. Cohort profile: Greifswald approach to individualized medicine (GANI_MED). J Transl Med. 2014;12:144.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Auffray C, Balling R, Barroso I, Bencze L, Benson M, Bergeron J, Bernal-Delgado E, Blomberg N, Bock C, Conesa A, Del Signore S, Delogne C, Devilee P, Di Meglio A, Eijkemans M, Flicek P, Graf N, Grimm V, Guchelaar HJ, Guo YK, Gut IG, Hanbury A, Hanif S, Hilgers RD, Honrado A, Hose DR, Houwing-Duistermaat J, Hubbard T, Janacek SH, Karanikas H, Kievits T, Kohler M, Kremer A, Lanfear J, Lengauer T, Maes E, Meert T, Muller W, Nickel D, Oledzki P, Pedersen B, Petkovic M, Pliakos K, Rattray M, I Màs JR, Schneider R, Sengstag T, Serra-Picamal X, Spek W, Vaas LA, Van Batenburg O, Vandelaer M, Varnai P, Villoslada P, Vizcaino JA, Wubbe JP, Zanetti G. Making sense of big data in health research: Towards an EU action plan. Genome Med. 2016;8:71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Hazin R, Brothers KB, Malin BA, Koenig BA, Sanderson SC, Rothstein MA, Williams MS, Clayton EW, Kullo IJ. Ethical, legal, and social implications of incorporating genomic information into electronic health records. Genet Med. 2013;15:810–6.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Lamas E, Barh A, Brown D, Jaulent MC. Ethical, Legal and Social Issues related to the health data-warehouses: re-using health data in the research and public health research. Stud Health Technol Inform. 2015;210:719–23.

    PubMed  Google Scholar 

  84. Vasan RS, Benjamin EJ. The future of cardiovascular epidemiology. Circulation. 2016;133:2626–33.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Horak P, Klink B, Heining C, Groschel S, Hutter B, Frohlich M, Uhrig S, Hubschmann D, Schlesner M, Eils R, Richter D, Pfutze K, Georg C, Meissburger B, Wolf S, Schulz A, Penzel R, Herpel E, Kirchner M, Lier A, Endris V, Singer S, Schirmacher P, Weichert W, Stenzinger A, Schlenk RF, Schrock E, Brors B, Von Kalle C, Glimm H, Frohling S. Precision oncology based on omics data: The NCT Heidelberg experience. Int J Cancer. 2017;141:877–86.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Faculty of Medicine, Institute of Medical Bioinformatics and Systems Medicine, University Medical Center, University of Freiburg, Freiburg, Germany

    Melanie Boerries

  2. German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany

    Melanie Boerries

  3. German Cancer Research Center (DKFZ), Heidelberg, Germany

    Melanie Boerries

  4. Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany

    Tanja Zeller

  5. German Center for Cardiovascular Research (DZHK), Partner site Hamburg/Lübeck/Kiel, Hamburg, Germany

    Tanja Zeller

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  1. Melanie Boerries
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  2. Tanja Zeller
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Correspondence to Tanja Zeller .

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  1. IIEG, University of Lubeck, Lübeck, Germany

    Jeanette Erdmann

  2. I Medical Dept (Cardiology), Klinikum Rechts der Isar of the Technical University Munich, München, Bayern, Germany

    Alessandra Moretti

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Boerries, M., Zeller, T. (2019). Systems Medicine as a Transforming Tool for Cardiovascular Genetics. In: Erdmann, J., Moretti, A. (eds) Genetic Causes of Cardiac Disease. Cardiac and Vascular Biology, vol 7. Springer, Cham. https://doi.org/10.1007/978-3-030-27371-2_11

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