Integrative network analysis reveals molecular mechanisms of blood pressure regulation

Molecular Systems Biology

Volumn 11, Issue 4, 2015, Pages 1-15

  Huan, Tianxiao ^a,b   Meng, Qingying ^c   Saleh, Mohamed A ^d,e   Norlander, Allison E ^a,b,f,g,h   Joehanes, Roby ⁱ   Zhu, Jun ^a,b   Chen, Brian H ⁱ   Zhang, Bin ⁱ   Johnson, Andrew D ^a,b   Ying, Saixia ^f   Courchesne, Paul ^a,b   Raghavachari, Nalini ^j   Wang, Richard ^b   Liu, Poching ^b   O'Donnell, Christopher J ^a,b   Vasan, Ramachandran ^a   Munson, Peter J ^f   Madhur, Meena S ^d   Harrison, David G ^d   Yang, Xia ^c   Levy, Daniel ^a,b   more..

^a FRAMINGHAM HEART STUDY   (United States)

^b NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^e MANSOURA UNIVERSITY   (Egypt)

^f NATIONAL INSTITUTES OF HEALTH   (United States)

^g HARVARD MEDICAL SCHOOL   (United States)

^h Hebrew Senior Life   (United States)

ⁱ MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^j NATIONAL INSTITUTE ON AGING   (United States)

more..

Author keywords

blood pressure; coexpression network; gene expression; hypertension; systems biology

Indexed keywords

ANGIOTENSIN II; MESSENGER RNA; LNK PROTEIN, MOUSE; SIGNAL PEPTIDE; TRANSCRIPTOME;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD PRESSURE REGULATION; CLINICAL ARTICLE; FEMALE; GENE; GENE EXPRESSION PROFILING; GENE REGULATORY NETWORK; GENETIC ASSOCIATION; HUMAN; HYPERTENSION; MALE; MIDDLE AGED; MOLECULAR INTERACTION; NONHUMAN; PRESSOR RESPONSE; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSCRIPTOMICS; AGED; ANIMAL; BLOOD PRESSURE; BODY MASS; COHORT ANALYSIS; DISEASE MODEL; GENE LOCUS; GENETICS; GENOME-WIDE ASSOCIATION STUDY; KNOCKOUT MOUSE; METABOLISM; MOUSE; PROTEIN DOMAIN; SEQUENCE ANALYSIS; STATISTICAL MODEL; SYSTEMS BIOLOGY; YOUNG ADULT;

MUS;

ADULT; AGED; ANGIOTENSIN II; ANIMALS; BLOOD PRESSURE; BODY MASS INDEX; COHORT STUDIES; DISEASE MODELS, ANIMAL; FEMALE; GENE REGULATORY NETWORKS; GENETIC LOCI; GENOME-WIDE ASSOCIATION STUDY; HUMANS; HYPERTENSION; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LINEAR MODELS; MALE; MICE; MICE, KNOCKOUT; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEIN INTERACTION DOMAINS AND MOTIFS; RNA, MESSENGER; SEQUENCE ANALYSIS, RNA; SYSTEMS BIOLOGY; TRANSCRIPTOME; YOUNG ADULT;

EID: 84979859262     PISSN: None     EISSN: 17444292     Source Type: Journal    
DOI: 10.15252/msb.20145399     Document Type: Article

References (78)

1. Abecasis GR, Cardon LR, Cookson WO, Sham PC, Cherny SS, (2001) Association analysis in a variance components framework. Genet Epidemiol 21 (Suppl 1): S341-S346
2. Ardanaz N, Yang X-P, Cifuentes ME, Haurani MJ, Jackson KW, Liao T-D, Carretero OA, Pagano PJ, (2010) Lack of glutathione peroxidase 1 accelerates cardiac-specific hypertrophy and dysfunction in angiotensin II hypertension. Hypertension 55: 116-123
3. 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, (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25: 25-29
4. Atkinson C, Stewart S, Upton PD, Machado R, Thomson JR, Trembath RC, Morrell NW, (2002) Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation 105: 1672-1678
5. Barabási A-L, Gulbahce N, Loscalzo J, (2011) Network medicine: a network-based approach to human disease. Nat Rev Genet 12: 56-68
6. Barhoumi T, Kasal DA, Li MW, Shbat L, Laurant P, Neves MF, Paradis P, Schiffrin EL, (2011) T Regulatory lymphocytes prevent angiotensin ii-induced hypertension and vascular injury. Hypertension 57: 469-476
7. Battle A, Mostafavi S, Zhu X, Potash JB, Weissman MM, McCormick C, Haudenschild CD, Beckman KB, Shi J, Mei R, (2014) Characterizing the genetic basis of transcriptome diversity through RNA-sequencing of 922 individuals. Genome Res 24: 14-24
8. Benjamini Y, Hochberg Y, (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B 57: 289-300
9. Bernal-Mizrachi C, Weng S, Feng C, Finck BN, Knutsen RH, Leone TC, Coleman T, Mecham RP, Kelly DP, Semenkovich CF, (2003) Dexamethasone induction of hypertension and diabetes is PPAR-α dependent in LDL receptor-null mice. Nat Med 9: 1069-1075
10. Bernal-Mizrachi C, Xiaozhong L, Yin L, Knutsen RH, Howard MJ, Arends JJ, DeSantis P, Coleman T, Semenkovich CF, (2007) An afferent vagal nerve pathway links hepatic PPARα activation to glucocorticoid-induced insulin resistance and hypertension. Cell Metab 5: 91-102
11. Chatr-Aryamontri A, Breitkreutz BJ, Heinicke S, Boucher L, Winter A, Stark C, Nixon J, Ramage L, Kolas N, O'Donnell L, Reguly T, Breitkreutz A, Sellam A, Chen D, Chang C, Rust J, Livstone M, Oughtred R, Dolinski K, Tyers M, (2013) The BioGRID interaction database: 2013 update. Nucleic Acids Res 41: D816-D823
12. Chen Y, Zhu J, Lum PY, Yang X, Pinto S, MacNeil DJ, Zhang C, Lamb J, Edwards S, Sieberts SK, Leonardson A, Castellini LW, Wang S, Champy MF, Zhang B, Emilsson V, Doss S, Ghazalpour A, Horvath S, Drake TA, et al., (2008) Variations in DNA elucidate molecular networks that cause disease. Nature 452: 429-435
13. Cho HM, Lee DY, Kim HY, Lee HA, Seok YM, Kim IK, (2012) Upregulation of the Na(+)-K(+)-2Cl(-) cotransporter 1 via histone modification in the aortas of angiotensin II-induced hypertensive rats. Hypertens Res 35: 819-824
14. Choate KA, Kahle KT, Wilson FH, Nelson-Williams C, Lifton RP, (2003) WNK1, a kinase mutated in inherited hypertension with hyperkalemia, localizes to diverse Cl- -transporting epithelia. Proc Natl Acad Sci USA 100: 663-668
15. Choi HJ, Yun HS, Kang HJ, Ban H-J, Kim Y, Nam H-Y, Hong E-J, Jung S-Y, Jung SE, Jeon J-P, (2012) Human transcriptome analysis of acute responses to glucose ingestion reveals the role of leukocytes in hyperglycemia-induced inflammation. Physiol Genomics 44: 1179-1187
16. Civelek M, Lusis AJ, (2014) Systems genetics approaches to understand complex traits. Nat Rev Genet 15: 34-48
17. Connolly MJ, Aaronson PI, (2011) Key role of the RhoA/Rho kinase system in pulmonary hypertension. Pulm Pharmacol Ther 24: 1-14
18. Cunningham JT, Fleming T, Penny ML, Herrera-Rosales M, Mifflin SW, (2006) Increased c-Fos in medullary cardiovascular nuclei in acute and chronic renal wrap hypertension. FASEB J 20: A1205-A1206
19. Cusick ME, Klitgord N, Vidal M, Hill DE, (2005) Interactome: gateway into systems biology. Hum Mol Genet 14: R171-R181
20. Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, Chasman DI, Smith AV, Tobin MD, Verwoert GC, Hwang SJ, Pihur V, Vollenweider P, O'Reilly PF, Amin N, Bragg-Gresham JL, Teumer A, Glazer NL, Launer L, Zhao JH, Aulchenko Y, et al., (2011) Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478: 103-109
21. Ehret GB, Caulfield MJ, (2013) Genes for blood pressure: an opportunity to understand hypertension. Eur Heart J 34: 951-961
22. Emilsson V, Thorleifsson G, Zhang B, Leonardson AS, Zink F, Zhu J, Carlson S, Helgason A, Walters GB, Gunnarsdottir S, Mouy M, Steinthorsdottir V, Eiriksdottir GH, Bjornsdottir G, Reynisdottir I, Gudbjartsson D, Helgadottir A, Jonasdottir A, Styrkarsdottir U, Gretarsdottir S, et al., (2008) Genetics of gene expression and its effect on disease. Nature 452: 423-428
23. Fehrmann RS, Jansen RC, Veldink JH, Westra H-J, Arends D, Bonder MJ, Fu J, Deelen P, Groen HJ, Smolonska A, (2011) Trans-eQTLs reveal that independent genetic variants associated with a complex phenotype converge on intermediate genes, with a major role for the HLA. PLoS Genet 7: e1002197
24. Feinleib M, Kannel WB, Garrison RJ, McNamara PM, Castelli WP, (1975) The Framingham offspring study. Design and preliminary data. Prev Med 4: 518-525
25. Goh K-I, Cusick ME, Valle D, Childs B, Vidal M, Barabási A-L, (2007) The human disease network. Proc Natl Acad Sci 104: 8685-8690
26. Groop LC, Kankuri M, Schalin-Jantti C, Ekstrand A, Nikula-Ijas P, Widen E, Kuismanen E, Eriksson J, Franssila-Kallunki A, Saloranta C, (1993) Association between polymorphism of the glycogen synthase gene and non-insulin-dependent diabetes mellitus. N Engl J Med 328: 10-14
27. Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, Goronzy J, Weyand C, Harrison DG, (2007) Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med 204: 2449-2460
28. Hamid R, Cogan JD, Hedges LK, Austin E, Phillips JA, Newman JH, Loyd JE, (2009) Penetrance of Pulmonary Arterial Hypertension Is Modulated by the Expression of Normal BMPR2 Allele. Hum Mutat 30: 649-654
29. Harrison DG, Vinh A, Lob H, Madhur MS, (2010) Role of the adaptive immune system in hypertension. Curr Opin Pharmacol 10: 203-207
30. Harrison DG, Guzik TJ, Lob HE, Madhur MS, Marvar PJ, Thabet SR, Vinh A, Weyand CM, (2011) Inflammation, immunity, and hypertension. Hypertension 57: 132-140
31. Harrison DG, Marvar PJ, Titze JM, (2012) Vascular inflammatory cells in hypertension. Front Physiol 3: 128
32. Hiebert PR, Granville DJ, (2012) Granzyme B in injury, inflammation, and repair. Trends Mol Med 18: 732-741
33. Huan T, Zhang B, Wang Z, Joehanes R, Zhu J, Johnson AD, Ying S, Munson PJ, Raghavachari N, Wang R, Liu P, Courchesne P, Hwang SJ, Assimes TL, McPherson R, Samani NJ, Schunkert H, Meng Q, Suver C, O'Donnell CJ, et al., (2013) A systems biology framework identifies molecular underpinnings of coronary heart disease. Arterioscler Thromb Vasc Biol 33: 1427-1434
34. Joehanes R, Ying S, Huan T, Johnson AD, Raghavachari N, Wang R, Liu P, Woodhouse KA, Sen SK, Tanriverdi K, (2013a) Gene expression signatures of coronary heart disease. Arterioscler Thromb Vasc Biol 33: 1418-1426
35. Joehanes R, Huan T, Yao C, Zhang X, Ying S, Feolo M, Sharapova N, Przytycka T, Sturcke A, Schaffer AA, Heard-Costa N, Liu P, Wang R, Woodhouse KA, Raghavachari N, Dupuis J, Johnson AD, O'Donnell CJ, Munson PJ, Levy D, (2013b) Genome-wide Expression Quantitative Trait Loci: Results from the NHLBI's SABRe CVD Initiative. The American Society of Human Genetics (ASHG) conference; Oct 22-26 2013; Boston Convention Ctr. Boston, MA
36. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J, (2005) Global burden of hypertension: analysis of worldwide data. Lancet 365: 217-223
37. Keshava Prasad TS, Goel R, Kandasamy K, Keerthikumar S, Kumar S, Mathivanan S, Telikicherla D, Raju R, Shafreen B, Venugopal A, Balakrishnan L, Marimuthu A, Banerjee S, Somanathan DS, Sebastian A, Rani S, Ray S, Harrys Kishore CJ, Kanth S, Ahmed M, et al., (2009) Human Protein Reference Database-2009 update. Nucleic Acids Res 37: D767-D772
38. Kirabo A, Fontana V, de Faria AP, Loperena R, Galindo CL, Wu J, Bikineyeva AT, Dikalov S, Xiao L, Chen W, (2014) DC isoketal-modified proteins activate T cells and promote hypertension. J Clin Investig 124
39. Kokubo Y, Tomoike H, Tanaka C, Banno M, Okuda T, Inamoto N, Kamide K, Kawano Y, Miyata T, (2006) Association of sixty-one non-synonymous polymorphisms in forty-one hypertension candidate genes with blood pressure variation and hypertension. Hypertens Res 29: 611-619
40. Koschinsky ML, Boffa MB, Nesheim ME, Zinman B, Hanley AJ, Harris SB, Cao H, Hegele RA, (2001) Association of a single nucleotide polymorphism in CPB2 encoding the thrombin-activable fibrinolysis inhibitor (TAF1) with blood pressure. Clin Genet 60: 345-349
41. Langfelder P, Horvath S, (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9: 559
42. Langfelder P, Zhang B, Horvath S, (2008) Defining clusters from a hierarchical cluster tree: the Dynamic Tree Cut package for R. Bioinformatics 24: 719-720
43. Lappalainen T, Sammeth M, Friedländer MR, AC't HP, Monlong J, Rivas MA, Gonzàlez-Porta M, Kurbatova N, Griebel T, Ferreira PG, (2013) Transcriptome and genome sequencing uncovers functional variation in humans. Nature 501: 506-511
44. Lawes CM, Vander Hoorn S, Law MR, Elliott P, MacMahon S, Rodgers A, (2006) Blood pressure and the global burden of disease 2000. Part II: estimates of attributable burden. J Hypertens 24: 423-430
45. Lee H-A, Cho H-M, Lee D-Y, Kim K-C, Han HS, Kim IK, (2012) Tissue-specific upregulation of angiotensin-converting enzyme 1 in spontaneously hypertensive rats through histone code modifications. Hypertension 59: 621-626
46. Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A, Glazer NL, Morrison AC, Johnson AD, Aspelund T, Aulchenko Y, Lumley T, Kottgen A, Vasan RS, Rivadeneira F, Eiriksdottir G, Guo X, Arking DE, Mitchell GF, Mattace-Raso FU, et al., (2009) Genome-wide association study of blood pressure and hypertension. Nat Genet 41: 677-687
47. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, (2002) Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360: 1903-1913
48. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, (2009) The sequence alignment/map format and SAMtools. Bioinformatics 25: 2078-2079
49. Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR, (2010) MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol 34: 816-834
50. Lindgren CM, Nilsson A, Orho-Melander M, Almgren P, Groop LC, (2001) Characterization of the annexin I gene and evaluation of its role in type 2 diabetes. Diabetes 50: 2402-2405
51. Lou Y, Liu J, Huang Y, Liu J, Wang Z, Liu Y, Li Z, Li Y, Xie Y, Wen S, (2010) A46G and C79G polymorphisms in the β2-adrenergic receptor gene (ADRB2) and essential hypertension risk: a meta-analysis. Hypertens Res 33: 1114-1123
52. Mäkinen V-P, Civelek M, Meng Q, Zhang B, Zhu J, Levian C, Huan T, Segrè AV, Ghosh S, Vivar J, (2014) Integrative genomics reveals novel molecular pathways and gene networks for coronary artery disease. PLoS Genet 10: e1004502
53. Marks AR, (2003) Calcium and the heart: a question of life and death. J Clin Investig 111: 597
54. Marvar PJ, Thabet SR, Guzik TJ, Lob HE, McCann LA, Weyand C, Gordon FJ, Harrison DG, (2010) Central and peripheral mechanisms of T-lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension. Circ Res 107: 263-270
55. Maunakea AK, Chepelev I, Zhao K, (2010) Epigenome mapping in normal and disease States. Circ Res 107: 327-339
56. Minson J, Arnolda L, Llewellyn-Smith I, Pilowsky P, Chalmers J, (1996) Altered c-fos in rostral medulla and spinal cord of spontaneously hypertensive rats. Hypertension 27: 433-441
57. Oishi Y, Manabe I, Imai Y, Hara K, Horikoshi M, Fujiu K, Tanaka T, Aizawa T, Kadowaki T, Nagai R, (2010) Regulatory polymorphism in transcription factor KLF5 at the MEF2 element alters the response to angiotensin II and is associated with human hypertension. FASEB J 24: 1780-1788
58. Orho-Melander M, Almgren P, Kanninen T, Forsblom C, Groop LC, (1999) A paired-sibling analysis of the XbaI polymorphism in the muscle glycogen synthase gene. Diabetologia 42: 1138-1145
59. 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, Titze J, Levy D, Harrison DG, Madhur MS, (2015) Lymphocyte adaptor protein LNK deficiency exacerbates hypertension and end-organ inflammation. J Clin Investig 125: 1189-1202
60. Satou R, Miyata K, Gonzalez-Villalobos RA, Ingelfinger JR, Navar LG, Kobori H, (2012) Interferon-γ biphasically regulates angiotensinogen expression via a JAK-STAT pathway and suppressor of cytokine signaling 1 (SOCS1) in renal proximal tubular cells. FASEB J 26: 1821-1830
61. Shanmugam N, Todorov I, Nair I, Omori K, Reddy M, Natarajan R, (2006) Increased expression of cyclooxygenase-2 in human pancreatic islets treated with high glucose or ligands of the advanced glycation endproduct-specific receptor (AGER), and in islets from diabetic mice. Diabetologia 49: 100-107
62. Splansky GL, Corey D, Yang Q, Atwood LD, Cupples LA, Benjamin EJ, D'Agostino RB Sr, Fox CS, Larson MG, Murabito JM, O'Donnell CJ, Vasan RS, Wolf PA, Levy D, (2007) The Third Generation Cohort of the National Heart, Lung, and Blood Institute's Framingham Heart Study: design, recruitment, and initial examination. Am J Epidemiol 165: 1328-1335
63. Storey JD, Tibshirani R, (2003) Statistical significance for genomewide studies. Proc Natl Acad Sci 100: 9440-9445
64. Tabara Y, Kohara K, Kita Y, Hirawa N, Katsuya T, Ohkubo T, Hiura Y, Tajima A, Morisaki T, Miyata T, (2010) Common Variants in the ATP2B1 Gene Are Associated With Susceptibility to Hypertension The Japanese Millennium Genome Project. Hypertension 56: 973-980
65. Takaki S, Sauer K, Iritani BM, Chien S, Ebihara Y, Tsuji K, Takatsu K, Perlmutter RM, (2000) Control of B cell production by the adaptor protein lnk. Definition Of a conserved family of signal-modulating proteins. Immunity 13: 599-609
66. Takizawa H, Eto K, Yoshikawa A, Nakauchi H, Takatsu K, Takaki S, (2008) Growth and maturation of megakaryocytes is regulated by Lnk/Sh2b3 adaptor protein through crosstalk between cytokine-and integrin-mediated signals. Exp Hematol 36: 897-906
67. Tang C, Oram JF, (2009) The cell cholesterol exporter ABCA1 as a protector from cardiovascular disease and diabetes. Biochim Biophys Acta 1791: 563-572
68. Trapnell C, Pachter L, Salzberg SL, (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25: 1105-1111
69. Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, Salzberg SL, Wold BJ, Pachter L, (2010) Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol 28: 511-515
70. Wang IM, Zhang B, Yang X, Zhu J, Stepaniants S, Zhang C, Meng Q, Peters M, He Y, Ni C, Slipetz D, Crackower MA, Houshyar H, Tan CM, Asante-Appiah E, O'Neill G, Luo MJ, Thieringer R, Yuan J, Chiu CS, et al., (2012) Systems analysis of eleven rodent disease models reveals an inflammatome signature and key drivers. Mol Syst Biol 8: 594
71. Westra H-J, Peters MJ, Esko T, Yaghootkar H, Schurmann C, Kettunen J, Christiansen MW, Fairfax BP, Schramm K, Powell JE, (2013) Systematic identification of trans eQTLs as putative drivers of known disease associations. Nat Genet 45: 1238-1243
72. Wright FA, Sullivan PF, Brooks AI, Zou F, Sun W, Xia K, Madar V, Jansen R, Chung W, Zhou Y-H, (2014) Heritability and genomics of gene expression in peripheral blood. Nat Genet 46: 430-437
73. Zhang B, Gaiteri C, Bodea LG, Wang Z, McElwee J, Podtelezhnikov AA, Zhang C, Xie T, Tran L, Dobrin R, Fluder E, Clurman B, Melquist S, Narayanan M, Suver C, Shah H, Mahajan M, Gillis T, Mysore J, MacDonald ME, et al., (2013) Integrated systems approach identifies genetic nodes and networks in late-ons, et al., zheimer's disease. Cell 153: 707-720
74. Zhang B, Horvath S, (2005) A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol 4: Article 17
75. Zhang N, (2011) The role of endogenous aryl hydrocarbon receptor signaling in cardiovascular physiology. J Cardiovasc Dis Res 2: 91-95
76. Zhong H, Yang X, Kaplan LM, Molony C, Schadt EE, (2010) Integrating pathway analysis and genetics of gene expression for genome-wide association studies. Am J Hum Genet 86: 581-591
77. Zhu J, Lum PY, Lamb J, GuhaThakurta D, Edwards SW, Thieringer R, Berger JP, Wu MS, Thompson J, Sachs AB, Schadt EE, (2004) An integrative genomics approach to the reconstruction of gene networks in segregating populations. Cytogenet Genome Res 105: 363-374
78. Zhu J, Wiener MC, Zhang C, Fridman A, Minch E, Lum PY, Sachs JR, Schadt EE, (2007) Increasing the power to detect causal associations by combining genotypic and expression data in segregating populations. PLoS Comput Biol 3: e69