Skip to main content
SpringerLink
Log in

A systematic heritability analysis of the human whole blood transcriptome

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

Genome-wide expressio n quantitative trait locus (eQTL) mapping may reveal common genetic variants regulating gene expression. In addition to mapping eQTLs, we systematically evaluated the heritability of the whole blood transcriptome in 5,626 participants from the Framingham Heart Study. Of all gene expression measurements, about 40 % exhibit evidence of being heritable [\(h_{\text{geneExp}}^{ 2}\) > 0, (p < 0.05)], the average heritability was estimated to be 0.13, and 10 % display \(h_{\text{geneExp}}^{ 2}\) > 0.2. To identify the role of eQTLs in promoting phenotype differences and disease susceptibility, we investigated the proportion of cis/trans eQTLs in different heritability categories and discovered that genes with higher heritability are more likely to have cis eQTLs that explain large proportions of variance in the expression of the corresponding genes. Single cis eQTLs explain 0.33–0.53 of variance in transcripts on average, whereas single trans eQTLs only explain 0.02–0.07. The top cis eQTLs tend to explain more variance in the corresponding gene when its \(h_{\text{geneExp}}^{ 2}\) is greater. Taking body mass index (BMI) as a case study, we cross-linked cis/trans eQTLs with both GWAS SNPs and differentially expressed genes for BMI. We discovered that BMI GWAS SNPs in 16p11.2 (e.g., rs7359397) are associated with several BMI differentially expressed genes in a cis manner (e.g. SULT1A1, SPNS1, and TUFM). These BMI signature genes explain a much larger proportion of variance in BMI than do the GWAS SNPs. Our results shed light on the impact of eQTLs on the heritability of the human whole blood transcriptome and its relations to phenotype differences.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • 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

    PubMed  Google Scholar 

  • Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491:56–65

    Article  PubMed  Google Scholar 

  • Almasy L, Blangero J (1998) Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 62:1198–1211

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc Series B (Methodological) 289–300

  • Cheung VG, Spielman RS (2009) Genetics of human gene expression: mapping DNA variants that influence gene expression. Nat Rev Genet 10:595–604

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dixon AL, Liang L, Moffatt MF, Chen W, Heath S, Wong KC, Taylor J, Burnett E, Gut I, Farrall M, Lathrop GM, Abecasis GR, Cookson WO (2007) A genome-wide association study of global gene expression. Nat Genet 39:1202–1207

    Article  CAS  PubMed  Google Scholar 

  • 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, Heath S, Sober S, Parsa A, Luan J, Arora P, Dehghan A, Zhang F, Lucas G, Hicks AA, Jackson AU, Peden JF, Tanaka T, Wild SH, Rudan I, Igl W, Milaneschi Y, Parker AN, Fava C, Chambers JC, Fox ER, Kumari M, Go MJ, van der Harst P, Kao WH, Sjogren M, Vinay DG, Alexander M, Tabara Y, Shaw-Hawkins S, Whincup PH, Liu Y, Shi G, Kuusisto J, Tayo B, Seielstad M, Sim X, Nguyen KD, Lehtimaki T, Matullo G, Wu Y, Gaunt TR, Onland-Moret NC, Cooper MN, Platou CG, Org E, Hardy R, Dahgam S, Palmen J, Vitart V, Braund PS, Kuznetsova T, Uiterwaal CS, Adeyemo A, Palmas W, Campbell H, Ludwig B, Tomaszewski M, Tzoulaki I, Palmer ND, Aspelund T, Garcia M, Chang YP, O’Connell JR, Steinle NI, Grobbee DE, Arking DE, Kardia SL, Morrison AC, Hernandez D, Najjar S, McArdle WL, Hadley D, Brown MJ, Connell JM, Hingorani AD, Day IN, Lawlor DA, Beilby JP, Lawrence RW, Clarke R et al (2011) Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478:103–109

    Article  CAS  PubMed  Google Scholar 

  • 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, Magnusson KP, Stefansson H, Fossdal R, Kristjansson K, Gislason HG, Stefansson T, Leifsson BG, Thorsteinsdottir U, Lamb JR, Gulcher JR, Reitman ML, Kong A, Schadt EE, Stefansson K (2008) Genetics of gene expression and its effect on disease. Nature 452:423–428

    Article  CAS  PubMed  Google Scholar 

  • Feinleib M, Kannel WB, Garrison RJ, McNamara PM, Castelli WP (1975) The Framingham Offspring Study. Design and preliminary data. Prev Med 4:518–525

    Article  CAS  PubMed  Google Scholar 

  • Goring HHH, Curran JE, Johnson MP, Dyer TD, Charlesworth J, Cole SA, Jowett JBM, Abraham LJ, Rainwater DL, Comuzzie AG, Mahaney MC, Almasy L, MacCluer JW, Kissebah AH, Collier GR, Moses EK, Blangero J (2007) Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes. Nat Genet 39:1208–1216

    Article  PubMed  Google Scholar 

  • Grundberg E, Small KS, Hedman AK, Nica AC, Buil A, Keildson S, Bell JT, Yang TP, Meduri E, Barrett A, Nisbett J, Sekowska M, Wilk A, Shin SY, Glass D, Travers M, Min JL, Ring S, Ho KR, Thorleifsson G, Kong A, Thorsteindottir U, Ainali C, Dimas AS, Hassanali N, Ingle C, Knowles D, Krestyaninova M, Lowe CE, Di Meglio P, Montgomery SB, Parts L, Potter S, Surdulescu G, Tsaprouni L, Tsoka S, Bataille V, Durbin R, Nestle FO, O’Rahilly S, Soranzo N, Lindgren CM, Zondervan KT, Ahmadi KR, Schadt EE, Stefansson K, Smith GD, McCarthy MI, Deloukas P, Dermitzakis ET, Spector TD, R MTHE (2012) Mapping cis- and trans-regulatory effects across multiple tissues in twins. Nat Genet 44:1084–1089

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Guo Y, Lanktree MB, Taylor KC, Hakonarson H, Lange LA, Keating BJ, Fairfax BP, Elbers CC, Barnard J, Farrall M (2013) Gene-centric meta-analyses of 108 912 individuals confirm known body mass index loci and reveal three novel signals. Hum Mol Genet 22:184–201

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, Manolio TA (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA 106:9362–9367

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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, Derry J, Yang X, Levy D (2013) A systems biology framework identifies molecular underpinnings of coronary heart disease. Arterioscler Thromb Vasc Biol 33:1427–1434

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Joehanes R, Ying S, Huan T, Johnson AD, Raghavachari N, Wang R, Liu P, Woodhouse KA, Sen SK, Tanriverdi K, Courchesne P, Freedman JE, O’Donnell CJ, Levy D, Munson PJ (2013) Gene expression signatures of coronary heart disease. Arterioscler Thromb Vasc Biol 33:1418–1426

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kobayashi KS, van den Elsen PJ (2012) NLRC5: a key regulator of MHC class I-dependent immune responses. Nat Rev Immunol 12:813–820

    Article  CAS  PubMed  Google Scholar 

  • 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, Smith AV, Taylor K, Scharpf RB, Hwang SJ, Sijbrands EJ, Bis J, Harris TB, Ganesh SK, O’Donnell CJ, Hofman A, Rotter JI, Coresh J, Benjamin EJ, Uitterlinden AG, Heiss G, Fox CS, Witteman JC, Boerwinkle E, Wang TJ, Gudnason V, Larson MG, Chakravarti A, Psaty BM, van Duijn CM (2009) Genome-wide association study of blood pressure and hypertension. Nat Genet 41:677–687

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    Article  PubMed Central  PubMed  Google Scholar 

  • Lotta LA, Peyvandi F (2011) Addressing the complexity of cardiovascular disease by design. Lancet 377:356–358

    Article  PubMed  Google Scholar 

  • Monda KL, Chen GK, Taylor KC, Palmer C, Edwards TL, Lange LA, Ng MC, Adeyemo AA, Allison MA, Bielak LF (2013) A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat Genet 45:690–696

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Morris AP, Voight BF, Teslovich TM, Ferreira T, Segre AV, Steinthorsdottir V, Strawbridge RJ, Khan H, Grallert H, Mahajan A (2012) Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet 44:981–990

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Myers AJ, Gibbs JR, Webster JA, Rohrer K, Zhao A, Marlowe L, Kaleem M, Leung D, Bryden L, Nath P, Zismann VL, Joshipura K, Huentelman MJ, Hu-Lince D, Coon KD, Craig DW, Pearson JV, Holmans P, Heward CB, Reiman EM, Stephan D, Hardy J (2007) A survey of genetic human cortical gene expression. Nat Genet 39:1494–1499

    Article  CAS  PubMed  Google Scholar 

  • Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L, Najjar SS, Zhao JH, Heath SC, Eyheramendy S, Papadakis K, Voight BF, Scott LJ, Zhang F, Farrall M, Tanaka T, Wallace C, Chambers JC, Khaw KT, Nilsson P, van der Harst P, Polidoro S, Grobbee DE, Onland-Moret NC, Bots ML, Wain LV, Elliott KS, Teumer A, Luan J, Lucas G, Kuusisto J, Burton PR, Hadley D, McArdle WL, Brown M, Dominiczak A, Newhouse SJ, Samani NJ, Webster J, Zeggini E, Beckmann JS, Bergmann S, Lim N, Song K, Vollenweider P, Waeber G, Waterworth DM, Yuan X, Groop L, Orho-Melander M, Allione A, Di Gregorio A, Guarrera S, Panico S, Ricceri F, Romanazzi V, Sacerdote C, Vineis P, Barroso I, Sandhu MS, Luben RN, Crawford GJ, Jousilahti P, Perola M, Boehnke M, Bonnycastle LL, Collins FS, Jackson AU, Mohlke KL, Stringham HM, Valle TT, Willer CJ, Bergman RN, Morken MA, Doring A, Gieger C, Illig T, Meitinger T, Org E, Pfeufer A, Wichmann HE, Kathiresan S, Marrugat J, O’Donnell CJ, Schwartz SM, Siscovick DS, Subirana I, Freimer NB, Hartikainen AL, McCarthy MI, O’Reilly PF, Peltonen L, Pouta A, de Jong PE, Snieder H, van Gilst WH, Clarke R, Goel A, Hamsten A, Peden JF et al (2009) Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet 41:666–676

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Price AL, Helgason A, Thorleifsson G, McCarroll SA, Kong A, Stefansson K (2011) Single-tissue and cross-tissue heritability of gene expression via identity-by-descent in related or unrelated individuals. Plos Genet 7:e1001317

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, Boehnke M, Abecasis GR, Willer CJ (2010) LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26:2336–2337

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ramasamy A, Trabzuni D, Gibbs JR, Dillman A, Hernandez DG, Arepalli S, Walker R, Smith C, Ilori GP, Shabalin AA (2013) Resolving the polymorphism-in-probe problem is critical for correct interpretation of expression QTL studies. Nucleic Acids Res 41:e88–e88

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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 (2011) Integrating genome-wide genetic variations and monocyte expression data reveals trans-regulated gene modules in humans. PLoS Genet 7:e1002367

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schadt EE, Molony C, Chudin E, Hao K, Yang X, Lum PY, Kasarskis A, Zhang B, Wang S, Suver C, Zhu J, Millstein J, Sieberts S, Lamb J, GuhaThakurta D, Derry J, Storey JD, Avila-Campillo I, Kruger MJ, Johnson JM, Rohl CA, van Nas A, Mehrabian M, Drake TA, Lusis AJ, Smith RC, Guengerich FP, Strom SC, Schuetz E, Rushmore TH, Ulrich R (2008) Mapping the genetic architecture of gene expression in human liver. PLoS Biol 6:e107

    Article  PubMed Central  PubMed  Google Scholar 

  • Schunkert H, Konig IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, Preuss M, Stewart AF, Barbalic M, Gieger C, Absher D, Aherrahrou Z, Allayee H, Altshuler D, Anand SS, Andersen K, Anderson JL, Ardissino D, Ball SG, Balmforth AJ, Barnes TA, Becker DM, Becker LC, Berger K, Bis JC, Boekholdt SM, Boerwinkle E, Braund PS, Brown MJ, Burnett MS, Buysschaert I, Carlquist JF, Chen L, Cichon S, Codd V, Davies RW, Dedoussis G, Dehghan A, Demissie S, Devaney JM, Diemert P, Do R, Doering A, Eifert S, Mokhtari NE, Ellis SG, Elosua R, Engert JC, Epstein SE, de Faire U, Fischer M, Folsom AR, Freyer J, Gigante B, Girelli D, Gretarsdottir S, Gudnason V, Gulcher JR, Halperin E, Hammond N, Hazen SL, Hofman A, Horne BD, Illig T, Iribarren C, Jones GT, Jukema JW, Kaiser MA, Kaplan LM, Kastelein JJ, Khaw KT, Knowles JW, Kolovou G, Kong A, Laaksonen R, Lambrechts D, Leander K, Lettre G, Li M, Lieb W, Loley C, Lotery AJ, Mannucci PM, Maouche S, Martinelli N, McKeown PP, Meisinger C, Meitinger T, Melander O, Merlini PA, Mooser V, Morgan T, Muhleisen TW, Muhlestein JB, Munzel T, Musunuru K, Nahrstaedt J, Nelson CP, Nothen MM, Olivieri O et al (2011) Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet 43:333–338

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, Lango Allen H, Lindgren CM, Luan J, Magi R, Randall JC, Vedantam S, Winkler TW, Qi L, Workalemahu T, Heid IM, Steinthorsdottir V, Stringham HM, Weedon MN, Wheeler E, Wood AR, Ferreira T, Weyant RJ, Segre AV, Estrada K, Liang L, Nemesh J, Park JH, Gustafsson S, Kilpelainen TO, Yang J, Bouatia-Naji N, Esko T, Feitosa MF, Kutalik Z, Mangino M, Raychaudhuri S, Scherag A, Smith AV, Welch R, Zhao JH, Aben KK, Absher DM, Amin N, Dixon AL, Fisher E, Glazer NL, Goddard ME, Heard-Costa NL, Hoesel V, Hottenga JJ, Johansson A, Johnson T, Ketkar S, Lamina C, Li S, Moffatt MF, Myers RH, Narisu N, Perry JR, Peters MJ, Preuss M, Ripatti S, Rivadeneira F, Sandholt C, Scott LJ, Timpson NJ, Tyrer JP, van Wingerden S, Watanabe RM, White CC, Wiklund F, Barlassina C, Chasman DI, Cooper MN, Jansson JO, Lawrence RW, Pellikka N, Prokopenko I, Shi J, Thiering E, Alavere H, Alibrandi MT, Almgren P, Arnold AM, Aspelund T, Atwood LD, Balkau B, Balmforth AJ, Bennett AJ, Ben-Shlomo Y, Bergman RN, Bergmann S, Biebermann H, Blakemore AI, Boes T, Bonnycastle LL, Bornstein SR, Brown MJ, Buchanan TA et al (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 42:937–948

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Stranger BE, Forrest MS, Clark AG, Minichiello MJ, Deutsch S, Lyle R, Hunt S, Kahl B, Antonarakis SE, Tavare S, Deloukas P, Dermitzakis ET (2005) Genome-wide associations of gene expression variation in humans. PLoS Genet 1:e78

    Article  PubMed Central  PubMed  Google Scholar 

  • Stranger BE, Nica AC, Forrest MS, Dimas A, Bird CP, Beazley C, Ingle CE, Dunning M, Flicek P, Koller D, Montgomery S, Tavare S, Deloukas P, Dermitzakis ET (2007) Population genomics of human gene expression. Nat Genet 39:1217–1224

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tenesa A, Haley CS (2013) The heritability of human disease: estimation, uses and abuses. Nat Rev Genet 14:139–149

    Article  CAS  PubMed  Google Scholar 

  • Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ, Johansen CT, Fouchier SW, Isaacs A, Peloso GM, Barbalic M, Ricketts SL, Bis JC, Aulchenko YS, Thorleifsson G, Feitosa MF, Chambers J, Orho-Melander M, Melander O, Johnson T, Li X, Guo X, Li M, Shin Cho Y, Jin Go M, Jin Kim Y, Lee JY, Park T, Kim K, Sim X, Twee-Hee Ong R, Croteau-Chonka DC, Lange LA, Smith JD, Song K, Hua Zhao J, Yuan X, Luan J, Lamina C, Ziegler A, Zhang W, Zee RY, Wright AF, Witteman JC, Wilson JF, Willemsen G, Wichmann HE, Whitfield JB, Waterworth DM, Wareham NJ, Waeber G, Vollenweider P, Voight BF, Vitart V, Uitterlinden AG, Uda M, Tuomilehto J, Thompson JR, Tanaka T, Surakka I, Stringham HM, Spector TD, Soranzo N, Smit JH, Sinisalo J, Silander K, Sijbrands EJ, Scuteri A, Scott J, Schlessinger D, Sanna S, Salomaa V, Saharinen J, Sabatti C, Ruokonen A, Rudan I, Rose LM, Roberts R, Rieder M, Psaty BM, Pramstaller PP, Pichler I, Perola M, Penninx BW, Pedersen NL, Pattaro C, Parker AN, Pare G, Oostra BA, O’Donnell CJ, Nieminen MS, Nickerson DA, Montgomery GW, Meitinger T, McPherson R, McCarthy MI et al (2010) Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466:707–713

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Verlaan DJ, Berlivet S, Hunninghake GM, Madore AM, Lariviere M, Moussette S, Grundberg E, Kwan T, Ouimet M, Ge B, Hoberman R, Swiatek M, Dias J, Lam KC, Koka V, Harmsen E, Soto-Quiros M, Avila L, Celedon JC, Weiss ST, Dewar K, Sinnett D, Laprise C, Raby BA, Pastinen T, Naumova AK (2009) Allele-specific chromatin remodeling in the ZPBP2/GSDMB/ORMDL3 locus associated with the risk of asthma and autoimmune disease. Am J Hum Genet 85:377–393

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCulloch LJ, Ferreira T, Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, McCarroll SA, Langenberg C, Hofmann OM, Dupuis J, Qi L, Segre AV, van Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Bostrom KB, Bravenboer B, Bumpstead S, Burtt NP, Charpentier G, Chines PS, Cornelis M, Couper DJ, Crawford G, Doney ASF, Elliott KS, Elliott AL, Erdos MR, Fox CS, Franklin CS, Ganser M, Gieger C, Grarup N, Green T, Griffin S, Groves CJ, Guiducci C, Hadjadj S, Hassanali N, Herder C, Isomaa B, Jackson AU, Johnson PRV, Jorgensen T, Kao WHL, Klopp N, Kong A, Kraft P, Kuusisto J, Lauritzen T, Li M, Lieverse A, Lindgren CM, Lyssenko V, Marre M, Meitinger T, Midthjell K, Morken MA, Narisu N, Nilsson P, Owen KR, Payne F, Perry JRB, Petersen A-K, Platou C, Proenca C, Prokopenko I, Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R, Shields BM, Shrader P, Sigurdsson G, Sparso T, Strassburger K, Stringham HM, Sun Q, Swift AJ, Thorand B et al (2010) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 42:579–589

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zeller T, Wild P, Szymczak S, Rotival M, Schillert A, Castagne R, Maouche S, Germain M, Lackner K, Rossmann H, Eleftheriadis M, Sinning CR, Schnabel RB, Lubos E, Mennerich D, Rust W, Perret C, Proust C, Nicaud V, Loscalzo J, Hubner N, Tregouet D, Munzel T, Ziegler A, Tiret L, Blankenberg S, Cambien F (2010) Genetics and beyond—the transcriptome of human monocytes and disease susceptibility. PLoS One 5:e10693

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

D. L., C. L. and T.H. designed, directed, and supervised the project. D. L was responsible for funding of the project. T. H., C. L. and D. L. drafted the manuscript. P. C. organized the experiment material and data exchange. All authors participated in revising and editing the manuscripts. All authors have read and approved the final version of the manuscript.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Framingham Heart Study, Population Sciences Branch, National Heart, Lung and Blood Institute, 73 Mt. Wayte Avenue, Suite 2, Framingham, MA, 01702, USA

    Tianxiao Huan, Chunyu Liu, Roby Joehanes, Xiaoling Zhang, Brian H. Chen, Andrew D. Johnson, Chen Yao, Paul Courchesne, Christopher J. O’Donnell & Daniel Levy

  2. Division of Intramural Research, Population Sciences Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA

    Tianxiao Huan, Chunyu Liu, Roby Joehanes, Brian H. Chen, Chen Yao, Paul Courchesne & Daniel Levy

  3. Division of Computational Bioscience, Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD, USA

    Roby Joehanes & Peter J. Munson

  4. Harvard Medical School, Boston, MA, USA

    Roby Joehanes

  5. Hebrew SeniorLife, Boston, MA, USA

    Roby Joehanes

  6. Division of Intramural Research, Cardiovascular Epidemiology and Human Genomics Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA

    Xiaoling Zhang, Andrew D. Johnson & Christopher J. O’Donnell

Authors
  1. Tianxiao Huan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunyu Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roby Joehanes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoling Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Brian H. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrew D. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chen Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Paul Courchesne
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Christopher J. O’Donnell
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Peter J. Munson
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Daniel Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel Levy.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (XLSX 1044 kb)

Supplementary material 2 (DOCX 683 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huan, T., Liu, C., Joehanes, R. et al. A systematic heritability analysis of the human whole blood transcriptome. Hum Genet 134, 343–358 (2015). https://doi.org/10.1007/s00439-014-1524-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-014-1524-3

Keywords

Search

Navigation