Mapping novel pathways in cardiovascular disease using eqtl data: The past, present, and future of gene expression analysis.

Frontiers in Genetics

Volumn 3, Issue OCT, 2012, Pages 1-17

  Gupta, Rajat M ^a,b   Musunuru, Kiran ^a,b  

^a Harvard University   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84876709334     PISSN: None     EISSN: 16648021     Source Type: Journal    
DOI: 10.3389/fgene.2012.00232     Document Type: Review

References (28)

1. Hirschhorn JN. Genomewide association studies--illuminating biologic pathways. N Engl J Med. 2009;360(17):1699-1701.
2. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001;411(6837):599-603.
3. 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. Genetics of gene expression and its effect on disease. Nature. 2008;452(7186):423-428.
4. 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. A genome-wide association study of global gene expression. Nat Genet. 2007;39(10):1202-1207.
5. Min JL, Taylor JM, Richards JB, Watts T, Pettersson FH, Broxholme J, Ahmadi KR, Surdulescu GL, Lowy E, Gieger C, Newton-Cheh C, Perola M, Soranzo N, Surakka I, Lindgren CM, Ragoussis J, Morris AP, Cardon LR, Spector TD, Zondervan KT. The use of genome-wide eQTL associations in lymphoblastoid cell lines to identify novel genetic pathways involved in complex traits. PLoS One.6(7):e22070.
6. Ding J, Gudjonsson JE, Liang L, Stuart PE, Li Y, Chen W, Weichenthal M, Ellinghaus E, Franke A, Cookson W, Nair RP, Elder JT, Abecasis GR. Gene expression in skin and lymphoblastoid cells: Refined statistical method reveals extensive overlap in ciseQTL signals. Am J Hum Genet.87(6):779-789.
7. Innocenti F, Cooper GM, Stanaway IB, Gamazon ER, Smith JD, Mirkov S, Ramirez J, Liu W, Lin YS, Moloney C, Aldred SF, Trinklein ND, Schuetz E, Nickerson DA, Thummel KE, Rieder MJ, Rettie AE, Ratain MJ, Cox NJ, Brown CD. Identification, replication, and functional fine-mapping of expression quantitative trait loci in primary human liver tissue. PLoS Genet.7(5):e1002078.
8. Nicolae DL, Gamazon E, Zhang W, Duan S, Dolan ME, Cox NJ.s Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS. PLoS Genet.6(4):e1000888.
9. Musunuru K, Strong A, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV, Li X, Li H, Kuperwasser N, Ruda VM, Pirruccello JP, Muchmore B, Prokunina-Olsson L, Hall JL, Schadt EE, Morales CR, Lund-Katz S, Phillips MC, Wong J, Cantley W, Racie T, Ejebe KG, Orho-Melander M, Melander O, Koteliansky V, Fitzgerald K, Krauss RM, Cowan CA, Kathiresan S, Rader DJ. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature.466(7307):714-719.
10. Linsel-Nitschke P, Heeren J, Aherrahrou Z, Bruse P, Gieger C, Illig T, Prokisch H, Heim K, Doering A, Peters A, Meitinger T, Wichmann HE, Hinney A, Reinehr T, Roth C, Ortlepp JR, Soufi M, Sattler AM, Schaefer J, Stark K, Hengstenberg C, Schaefer A, Schreiber S, Kronenberg F, Samani NJ, Schunkert H, Erdmann J. Genetic variation at chromosome 1p13.3 affects sortilin mRNA expression, cellular LDL-uptake and serum LDL levels which translates to the risk of coronary artery disease. Atherosclerosis.208(1):183-189.
11. 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, McArdle W, Masson D, Martin NG, Marroni F, Mangino M, Magnusson PK, Lucas G, Luben R, Loos RJ, Lokki ML, Lettre G, Langenberg C, Launer LJ, Lakatta EG, Laaksonen R, Kyvik KO, Kronenberg F, Konig IR, Khaw KT, Kaprio J, Kaplan LM, Johansson A, Jarvelin MR, Janssens AC, Ingelsson E, Igl W, Kees Hovingh G, Hottenga JJ, Hofman A, Hicks AA, Hengstenberg C, Heid IM, Hayward C, Havulinna AS, Hastie ND, Harris TB, Haritunians T, Hall AS, Gyllensten U, Guiducci C, Groop LC, Gonzalez E, Gieger C, Freimer NB, Ferrucci L, Erdmann J, Elliott P, Ejebe KG, Doring A, Dominiczak AF, Demissie S, Deloukas P, de Geus EJ, de Faire U, Crawford G, Collins FS, Chen YD, Caulfield MJ, Campbell H, Burtt NP, Bonnycastle LL, Boomsma DI, Boekholdt SM, Bergman RN, Barroso I, Bandinelli S, Ballantyne CM, Assimes TL, Quertermous T, Altshuler D, Seielstad M, Wong TY, Tai ES, Feranil AB, Kuzawa CW, Adair LS, Taylor HA, Jr., Borecki IB, Gabriel SB, Wilson JG, Holm H, Thorsteinsdottir U, Gudnason V, Krauss RM, Mohlke KL, Ordovas JM, Munroe PB, Kooner JS, Tall AR, Hegele RA, Kastelein JJ, Schadt EE, Rotter JI, Boerwinkle E, Strachan DP, Mooser V, Stefansson K, Reilly MP, Samani NJ, Schunkert H, Cupples LA, Sandhu MS, Ridker PM, Rader DJ, van Duijn CM, Peltonen L, Abecasis GR, Boehnke M, Kathiresan S. Biological, clinical and population relevance of 95 loci for blood lipids. Nature.466(7307):707-713.
12. Wild PS, Zeller T, Schillert A, Szymczak S, Sinning CR, Deiseroth A, Schnabel RB, Lubos E, Keller T, Eleftheriadis MS, Bickel C, Rupprecht HJ, Wilde S, Rossmann H, Diemert P, Cupples LA, Perret C, Erdmann J, Stark K, Kleber ME, Epstein SE, Voight BF, Kuulasmaa K, Li M, Schafer AS, Klopp N, Braund PS, Sager HB, Demissie S, Proust C, Konig IR, Wichmann HE, Reinhard W, Hoffmann MM, Virtamo J, Burnett MS, Siscovick D, Wiklund PG, Qu L, El Mokthari NE, Thompson JR, Peters A, Smith AV, Yon E, Baumert J, Hengstenberg C, Marz W, Amouyel P, Devaney J, Schwartz SM, Saarela O, Mehta NN, Rubin D, Silander K, Hall AS, Ferrieres J, Harris TB, Melander O, Kee F, Hakonarson H, Schrezenmeir J, Gudnason V, Elosua R, Arveiler D, Evans A, Rader DJ, Illig T, Schreiber S, Bis JC, Altshuler D, Kavousi M, Witteman JC, Uitterlinden AG, Hofman A, Folsom AR, Barbalic M, Boerwinkle E, Kathiresan S, Reilly MP, O'Donnell CJ, Samani NJ, Schunkert H, Cambien F, Lackner KJ, Tiret L, Salomaa V, Munzel T, Ziegler A, Blankenberg S. A genome-wide association study identifies LIPA as a susceptibility gene for coronary artery disease. Circ Cardiovasc Genet.4(4):403-412.
13. Folkersen L, van't Hooft F, Chernogubova E, Agardh HE, Hansson GK, Hedin U, Liska J, Syvanen AC, Paulsson-Berne G, Franco-Cereceda A, Hamsten A, Gabrielsen A, Eriksson P. Association of genetic risk variants with expression of proximal genes identifies novel susceptibility genes for cardiovascular disease. Circ Cardiovasc Genet.3(4):365-373.
14. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nat Genet.43(4):339-344.
15. Helgadottir A, Thorleifsson G, Magnusson KP, Gretarsdottir S, Steinthorsdottir V, Manolescu A, Jones GT, Rinkel GJ, Blankensteijn JD, Ronkainen A, Jaaskelainen JE, Kyo Y, Lenk GM, Sakalihasan N, Kostulas K, Gottsater A, Flex A, Stefansson H, Hansen T, Andersen G, Weinsheimer S, Borch-Johnsen K, Jorgensen T, Shah SH, Quyyumi AA, Granger CB, Reilly MP, Austin H, Levey AI, Vaccarino V, Palsdottir E, Walters GB, Jonsdottir T, Snorradottir S, Magnusdottir D, Gudmundsson G, Ferrell RE, Sveinbjornsdottir S, Hernesniemi J, Niemela M, Limet R, Andersen K, Sigurdsson G, Benediktsson R, Verhoeven EL, Teijink JA, Grobbee DE, Rader DJ, Collier DA, Pedersen O, Pola R, Hillert J, Lindblad B, Valdimarsson EM, Magnadottir HB, Wijmenga C, Tromp G, Baas AF, Ruigrok YM, van Rij AM, Kuivaniemi H, Powell JT, Matthiasson SE, Gulcher JR, Thorgeirsson G, Kong A, Thorsteinsdottir U, Stefansson K. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet. 2008;40(2):217-224.
16. Cunnington MS, Santibanez Koref M, Mayosi BM, Burn J, Keavney B. Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression. PLoS Genet.6(4):e1000899.
17. Akey JM, Biswas S, Leek JT, Storey JD. On the design and analysis of gene expression studies in human populations. Nat Genet. 2007;39(7):807-808; author reply 808-809.
18. Barnes M, Freudenberg J, Thompson S, Aronow B, Pavlidis P. Experimental comparison and cross-validation of the Affymetrix and Illumina gene expression analysis platforms. Nucleic Acids Res. 2005;33(18):5914-5923.
19. Pedotti P, t Hoen PA, Vreugdenhil E, Schenk GJ, Vossen RH, Ariyurek Y, de Hollander M, Kuiper R, van Ommen GJ, den Dunnen JT, Boer JM, de Menezes RX. Can subtle changes in gene expression be consistently detected with different microarray platforms? BMC Genomics. 2008;9:124.
20. Leek JT, Scharpf RB, Bravo HC, Simcha D, Langmead B, Johnson WE, Geman D, Baggerly K, Irizarry RA. Tackling the widespread and critical impact of batch effects in high-throughput data. Nat Rev Genet.11(10):733-739.
21. Schadt EE, Monks SA, Drake TA, Lusis AJ, Che N, Colinayo V, Ruff TG, Milligan SB, Lamb JR, Cavet G, Linsley PS, Mao M, Stoughton RB, Friend SH. Genetics of gene expression surveyed in maize, mouse and man. Nature. 2003;422(6929):297-302.
22. Morley M, Molony CM, Weber TM, Devlin JL, Ewens KG, Spielman RS, Cheung VG. Genetic analysis of genome-wide variation in human gene expression. Nature. 2004;430(7001):743-747.
23. Cookson W, Liang L, Abecasis G, Moffatt M, Lathrop M. Mapping complex disease traits with global gene expression. Nat Rev Genet. 2009;10(3):184-194.
24. Plagnol V, Uz E, Wallace C, Stevens H, Clayton D, Ozcelik T, Todd JA. Extreme clonality in lymphoblastoid cell lines with implications for allele specific expression analyses. PLoS One. 2008;3(8):e2966.
25. 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. Mapping the genetic architecture of gene expression in human liver. PLoS Biol. 2008;6(5):e107.
26. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861-872.
27. Fox ER, Young JH, Li Y, Dreisbach AW, Keating BJ, Musani SK, Liu K, Morrison AC, Ganesh S, Kutlar A, Ramachandran VS, Polak JF, Fabsitz RR, Dries DL, Farlow DN, Redline S, Adeyemo A, Hirschorn JN, Sun YV, Wyatt SB, Penman AD, Palmas W, Rotter JI, Townsend RR, Doumatey AP, Tayo BO, Mosley TH, Jr., Lyon HN, Kang SJ, Rotimi CN, Cooper RS, Franceschini N, Curb JD, Martin LW, Eaton CB, Kardia SL, Taylor HA, Caulfield MJ, Ehret GB, Johnson T, Chakravarti A, Zhu X, Levy D, 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, 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, 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, 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, Hernandez D, Najjar S, McArdle WL, Hadley D, Brown MJ, Connell JM, Hingorani AD, Day IN, Lawlor DA, Beilby JP, Lawrence RW, Clarke R, Collins R, Hopewell JC, Ongen H, Bis JC, Kahonen M, Viikari J, Adair LS, Lee NR, Chen MH, Olden M, Pattaro C, Hoffman Bolton JA, Kottgen A, Bergmann S, Mooser V, Chaturvedi N, Frayling TM, Islam M, Jafar TH, Erdmann J, Kulkarni SR, Bornstein SR, Grassler J, Groop L, Voight BF, Kettunen J, Howard P, Taylor A, Guarrera S, Ricceri F, Emilsson V, Plump A, Barroso I, Khaw KT, Weder AB, Hunt SC, Bergman RN, Collins FS, Bonnycastle LL, Scott LJ, Stringham HM, Peltonen L, Perola M, Vartiainen E, Brand SM, Staessen JA, Wang TJ, Burton PR, Soler Artigas M, Dong Y, Snieder H, Wang X, Zhu H, Lohman KK, Rudock ME, Heckbert SR, Smith NL, Wiggins KL, Shriner D, Veldre G, Viigimaa M, Kinra S, Prabhakaran D, Tripathy V, Langefeld CD, Rosengren A, Thelle DS, Corsi AM, Singleton A, Forrester T, Hilton G, McKenzie CA, Salako T, Iwai N, Kita Y, Ogihara T, Ohkubo T, Okamura T, Ueshima H, Umemura S, Eyheramendy S, Meitinger T, Wichmann HE, Cho YS, Kim HL, Lee JY, Scott J, Sehmi JS, Zhang W, Hedblad B, Nilsson P, Smith GD, Wong A, Narisu N, Stancakova A, Raffel LJ, Yao J, Kathiresan S, O'Donnell C, Schwartz SM, Ikram MA, Longstreth WT, Jr., Seshadri S, Shrine NR, Wain LV, Morken MA, Swift AJ, Laitinen J, Prokopenko I, Zitting P, Cooper JA, Humphries SE, Danesh J, Rasheed A, Goel A, Hamsten A, Watkins H, Bakker SJ, van Gilst WH, Janipalli C, Mani KR, Yajnik CS, Hofman A, Mattace-Raso FU, Oostra BA, Demirkan A, Isaacs A, Rivadeneira F, Lakatta EG, Orru M, Scuteri A, Ala-Korpela M, Kangas AJ, Lyytikainen LP, Soininen P, Tukiainen T, Wurz P, Ong RT, Dorr M, Kroemer HK, Volker U, Volzke H, Galan P, Hercberg S, Lathrop M, Zelenika D, Deloukas P, Mangino M, Spector TD, Zhai G, Meschia JF, Nalls MA, Sharma P, Terzic J, Kumar MJ, Denniff M, Zukowska-Szczechowska E, Wagenknecht LE, Fowkes FG, Charchar FJ, Schwarz PE, Hayward C, Guo X, Bots ML, Brand E, Samani N, Polasek O, Talmud PJ, Nyberg F, Kuh D, Laan M, Hveem K, Palmer LJ, van der Schouw YT, Casas JP, Mohlke KL, Vineis P, Raitakari O, Wong TY, Tai ES, Laakso M, Rao DC, Harris TB, Morris RW, Dominiczak AF, Kivimaki M, Marmot MG, Miki T, Saleheen D, Chandak GR, Coresh J, Navis G, Salomaa V, Han BG, Kooner JS, Melander O, Ridker PM, Bandinelli S, Gyllensten UB, Wright AF, Wilson JF, Ferrucci L, Farrall M, Tuomilehto J, Pramstaller PP, Elosua R, Soranzo N, Sijbrands EJ, Altshuler D, Loos RJ, Shuldiner AR, Gieger C, Meneton P, Uitterlinden AG, Wareham NJ, Gudnason V, Rettig R, Uda M, Strachan DP, Witteman JC, Hartikainen AL, Beckmann JS, Boerwinkle E, Boehnke M, Larson MG, Jarvelin MR, Psaty BM, Abecasis GR, Elliott P, van Duijn CM, Newton-Cheh C. Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study. Hum Mol Genet.20(11):2273-2284.
28. 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. Genome-wide association study of blood pressure and hypertension. Nat Genet. 2009;41(6):677-687.