Association of genetic variants and incident coronary heart disease in multiethnic cohorts: The PAGE study

Circulation: Cardiovascular Genetics

Volumn 4, Issue 6, 2011, Pages 661-672

  Franceschini, Nora ^a   Carty, Cara ^b   Bužková, Petra ^o   Reiner, Alex P ^c   Garrett, Tiana ^a   Lin, Yi ^b   Vöckler, Jens S ^d   Hindorff, Lucia A ^e   Cole, Shelley A ^f   Boerwinkle, Eric ^e   Lin, Dan Yu ^a   Bookman, Ebony ^g   Best, Lyle G ^h   Bella, Jonathan N ⁱ   Eaton, Charles ^j   Greenland, Philip ^k   Jenny, Nancy ^l   North, Kari E ^a,m   Taverna, Darin ⁿ   Young, Alicia M ^b   Deelman, Ewa ^d   Kooperberg, Charles ^b   Psaty, Bruce ^c   Heiss, Gerardo ^a   more..

^a University of North Carolina at Chapel Hill   (United States)

^b Fred Hutchinson Cancer Research Center   (United States)

^c UNIVERSITY OF WASHINGTON   (United States)

^d UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^e NATIONAL HUMAN GENOME RESEARCH INSTITUTE   (United States)

^f SOUTHWEST FOUNDATION FOR BIOMEDICAL RESEARCH   (United States)

^g UNIVERSITY OF TEXAS   (United States)

^h MISSOURI BREAKS INDUSTRIES RESEARCH INC   (United States)

ⁱ ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^j BROWN UNIVERSITY   (United States)

^k NORTHWESTERN UNIVERSITY   (United States)

^l UNIVERSITY OF VERMONT COLLEGE OF MEDICINE   (United States)

^m UNIVERSITY OF NORTH CAROLINA   (United States)

ⁿ TRANSLATIONAL GENOMICS RESEARCH INSTITUTE   (United States)

^o UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

more..

Author keywords

9p21 locus; Genetic polymorphisms; Incident coronary heart disease

Indexed keywords

APOLIPOPROTEIN E; CHEMOKINE RECEPTOR CXCR4; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); SMAD3 PROTEIN;

AMERICAN INDIAN; ARTICLE; CORONARY ARTERY RECANALIZATION; ETHNICITY; FOLLOW UP; GENE LOCUS; GENE REPLICATION; GENETIC HETEROGENEITY; GENETIC RISK; GENETIC VARIABILITY; GENOTYPE; HISPANIC; INHERITANCE; ISCHEMIC HEART DISEASE; PACIFIC ISLANDER; PRIORITY JOURNAL; PROSPECTIVE STUDY; SINGLE NUCLEOTIDE POLYMORPHISM;

AGED; AGED, 80 AND OVER; CONTINENTAL POPULATION GROUPS; CORONARY DISEASE; FEMALE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MALE; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; PROSPECTIVE STUDIES;

EID: 84862969993     PISSN: 1942325X     EISSN: 19423268     Source Type: Journal    
DOI: 10.1161/CIRCGENETICS.111.960096     Document Type: Article

References (44)

1. Visel A, Zhu Y, May D, Afzal V, Gong E, Attanasio C, Blow MJ, Cohen JC, Rubin EM, Pennacchio LA. Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. Nature. 2010;464:409-412.
2. McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds DA, Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC. A common allele on chromosome 9 associated with coronary heart disease. Science. 2007;316:1488-1491. (Pubitemid 46906617)
3. Assimes TL, Knowles JW, Basu A, Iribarren C, Southwick A, Tang H, Absher D, Li J, Fair JM, Rubin GD, Sidney S, Fortmann SP, Go AS, Hlatky MA, Myers RM, Risch N, Quertermous T. Susceptibility locus for clinical and subclinical coronary artery disease at chromosome 9p21 in the multi-ethnic ADVANCE study. Hum Mol Genet. 2008;17: 2320-2328.
4. Matarin M, Brown WM, Singleton A, Hardy JA, Meschia JF. Whole genome analyses suggest ischemic stroke and heart disease share an association with polymorphisms on chromosome 9p21. Stroke. 2008;39: 1586-1589.
5. Yamagishi K, Folsom AR, Rosamond WD, Boerwinkle E. A genetic variant on chromosome 9p21 and incident heart failure in the ARIC study. Eur Heart J. 2009;30:1222-1228.
6. Cluett C, McDermott MM, Guralnik J, Ferrucci L, Bandinelli S, Miljkovic I, Zmuda JM, Li R, Tranah G, Harris T, Rice N, Henley W, Frayling TM, Murray A, Melzer D. The 9p21 myocardial infarction risk allele increases risk of peripheral artery disease in older people. Circ Cardiovasc Genet. 2009;2:347-353.
7. Helgadottir A, Thorleifsson G, Magnusson KP, Grétarsdottir 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;40:217-224. (Pubitemid 351171400)
8. Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, Jonasdottir A, Sigurdsson A, Baker A, Palsson A, Masson G, Gudbjartsson DF, Magnusson KP, Andersen K, Levey AI, Backman VM, Matthiasdottir S, Jonsdottir T, Palsson S, Einarsdottir H, Gunnarsdottir S, Gylfason A, Vaccarino V, Hooper WC, Reilly MP, Granger CB, Austin H, Rader DJ, Shah SH, Quyyumi AA, Gulcher JR, Thorgeirsson G, Thorsteinsdottir U, Kong A, Stefansson K. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007; 316:1491-1493. (Pubitemid 46906618)
9. Palomaki GE, Melillo S, Bradley LA. Association between 9p21 genomic markers and heart disease: a meta-analysis. Jama. 2010;303:648-656.
10. Bressler J, Folsom AR, Couper DJ, Volcik KA, Boerwinkle E. Genetic variants identified in a European genome-wide association study that were found to predict incident coronary heart disease in the atherosclerosis risk in communities study. Am J Epidemiol. 2010;171:14-23.
11. Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, Heath SC, Timpson NJ, Najjar SS, Stringham HM, Strait J, Duren WL, Maschio A, Busonero F, Mulas A, Albai G, Swift AJ, Morken MA, Narisu N, Bennett D, Parish S, Shen H, Galan P, Meneton P, Hercberg S, Zelenika D, Chen WM, Li Y, Scott LJ, Scheet PA, Sundvall J, Watanabe RM, Nagaraja R, Ebrahim S, Lawlor DA, Ben-Shlomo Y, Davey-Smith G, Shuldiner AR, Collins R, Bergman RN, Uda M, Tuomilehto J, Cao A, Collins FS, Lakatta E, Lathrop GM, Boehnke M, Schlessinger D, Mohlke KL, Abecasis GR. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 2008;40:161-169. (Pubitemid 351171403)
12. Kathiresan S, Melander O, Anevski D, Guiducci C, Burtt NP, Roos C, Hirschhorn JN, Berglund G, Hedblad B, Groop L, Altshuler DM, Newton-Cheh C, Orho-Melander M. Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med. 2008;358: 1240-1249. (Pubitemid 351439225)
13. Aulchenko YS, Ripatti S, Lindqvist I, Boomsma D, Heid IM, Pramstaller PP, Penninx BW, Janssens AC, Wilson JF, Spector T, Martin NG, Pedersen NL, Kyvik KO, Kaprio J, Hofman A, Freimer NB, Jarvelin MR, Gyllensten U, Campbell H, Rudan I, Johansson A, Marroni F, Hayward C, Vitart V, Jonasson I, Pattaro C, Wright A, Hastie N, Pichler I, Hicks AA, Falchi M, Willemsen G, Hottenga JJ, de Geus EJ, Montgomery GW, Whitfield J, Magnusson P, Saharinen J, Perola M, Silander K, Isaacs A, Sijbrands EJ, Uitterlinden AG, Witteman JC, Oostra BA, Elliott P, Ruokonen A, Sabatti C, Gieger C, Meitinger T, Kronenberg F, Doring A, Wichmann HE, Smit JH, McCarthy MI, van Duijn CM, Peltonen L. Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet. 2009;41:47-55.
14. Statistics. NCfH. Plan and operation of the third national health and nutrition examination survey, 1988-94 1994.
15. Kolonel LN, Henderson BE, Hankin JH, Nomura AM, Wilkens LR, Pike MC, Stram DO, Monroe KR, Earle ME, Nagamine FS. A multiethnic cohort in Hawaii and Los Angeles: baseline characteristics. Am J Epidemiol. 2000;151:346-357. (Pubitemid 30463612)
16. Design of the Women's Health Initiative clinical trial and observational study. The Women's Health Initiative Study Group. Control Clin Trials. 1998;19:61-109.
17. The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators. The aric investigators. Am J Epidemiol. 1989;129:687-702.
18. Hughes GH, Cutter G, Donahue R, Friedman GD, Hulley S, Hunkeler E, Jacobs DR, Jr., Liu K, Orden S, Pirie P. Recruitment in the Coronary Artery Disease Risk Development in Young Adults (Cardia) Study. Control Clin Trials. 1987;8:68S-73S.
19. Fried LP, Borhani NO, Enright P, Furberg CD, Gardin JM, Kronmal RA, Kuller LH, Manolio TA, Mittelmark MB, Newman A. The Cardiovascular Health Study: design and rationale. Ann Epidemiol. 1991;1: 263-276.
20. Lee ET, Welty TK, Fabsitz R, Cowan LD, Le NA, Oopik AJ, Cucchiara AJ, Savage PJ, Howard BV. The strong heart study. The Strong Heart Study. A study of cardiovascular disease in American Indians: design and methods. Am J Epidemiol. 1990;132:1141-1155.
21. North KE, Howard BV, Welty TK, Best LG, Lee ET, Yeh JL, Fabsitz RR, Roman MJ, MacCluer JW. Genetic and environmental contributions to cardiovascular disease risk in American Indians: the strong heart family study. Am J Epidemiol. 2003;157:303-314. (Pubitemid 36193933)
22. Curb JD, McTiernan A, Heckbert SR, Kooperberg C, Stanford J, Nevitt M, Johnson KC, Proulx-Burns L, Pastore L, Criqui M, Daugherty S. Outcomes ascertainment and adjudication methods in the Women's Health Initiative. Ann Epidemiol. 2003;13:S122-S128. (Pubitemid 37324181)
23. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447:661-678.
24. Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, Dixon RJ, Meitinger T, Braund P, Wichmann HE, Barrett JH, Konig IR, Stevens SE, Szymczak S, Tregouet DA, Iles MM, Pahlke F, Pollard H, Lieb W, Cambien F, Fischer M, Ouwehand W, Blankenberg S, Balmforth AJ, Baessler A, Ball SG, Strom TM, Braenne I, Gieger C, Deloukas P, Tobin MD, Ziegler A, Thompson JR, Schunkert H. Genomewide association analysis of coronary artery disease. N Engl J Med. 2007;357: 443-453. (Pubitemid 47204873)
25. Larson MG, Atwood LD, Benjamin EJ, Cupples LA, D'Agostino RB, Sr., Fox CS, Govindaraju DR, Guo CY, Heard-Costa NL, Hwang SJ, Murabito JM, Newton-Cheh C, O'Donnell CJ, Seshadri S, Vasan RS, Wang TJ, Wolf PA, Levy D. Framingham heart study 100k project: Genome-wide associations for cardiovascular disease outcomes. BMC Med Genet. 2007;8 Suppl 1:S5.
26. Sagoo GS, Tatt I, Salanti G, Butterworth AS, Sarwar N, van Maarle M, Jukema JW, Wiman B, Kastelein JJ, Bennet AM, de Faire U, Danesh J, Higgins JP. Seven lipoprotein lipase gene polymorphisms, lipid fractions, and coronary disease: a HuGE association review and meta-analysis. Am J Epidemiol. 2008;168:1233-1246.
27. Song Y, Stampfer MJ, Liu S. Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann Intern Med. 2004;141:137-147. (Pubitemid 38937836)
28. Kathiresan S, Voight BF, Purcell S, Musunuru K, Ardissino D, Mannucci PM, Anand S, Engert JC, Samani NJ, Schunkert H, Erdmann J, Reilly MP, Rader DJ, Morgan T, Spertus JA, Stoll M, Girelli D, McKeown PP, Patterson CC, Siscovick DS, O'Donnell CJ, Elosua R, Peltonen L, Salomaa V, Schwartz SM, Melander O, Altshuler D, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Casari G, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Yee J, Friedlander Y, Marrugat J, Lucas G, Subirana I, Sala J, Ramos R, Meigs JB, Williams G, Nathan DM, MacRae CA, Havulinna AS, Berglund G, Hirschhorn JN, Asselta R, Duga S, Spreafico M, Daly MJ, Nemesh J, Korn JM, McCarroll SA, Surti A, Guiducci C, Gianniny L, Mirel D, Parkin M, Burtt N, Gabriel SB, Thompson JR, Braund PS, Wright BJ, Balmforth AJ, Ball SG, Hall AS, Linsel-Nitschke P, Lieb W, Ziegler A, Konig I, Hengstenberg C, Fischer M, Stark K, Grosshennig A, Preuss M, Wichmann HE, Schreiber S, Ouwehand W, Deloukas P, Scholz M, Cambien F, Li M, Chen Z, Wilensky R, Matthai W, Qasim A, Hakonarson HH, Devaney J, Burnett MS, Pichard AD, Kent KM, Satler L, Lindsay JM, Waksman R, Epstein SE, Scheffold T, Berger K, Huge A, Martinelli N, Olivieri O, Corrocher R, McKeown P, Erdmann E, Konig IR, Holm H, Thorleifsson G, Thorsteinsdottir U, Stefansson K, Do R, Xie C, Siscovick D. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet. 2009;41:334-341.
29. Zondervan KT, Cardon LR. The complex interplay among factors that influence allelic association. Nat Rev Genet. 2004;5:89-100. (Pubitemid 38160276)
30. Psaty BM, O'Donnell CJ, Gudnason V, Lunetta KL, Folsom AR, Rotter JI, Uitterlinden AG, Harris TB, Witteman JC, Boerwinkle E. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: Design of prospective meta-analyses of genome-wide association studies from 5 cohorts. Circ Cardiovasc Genet. 2009;2:73-80.
31. Breslow NE. Discussion of professor cox's paper. J Royal Stat Soc B. 1972;34:216-217.
32. Kitsios GD, Dahabreh IJ, Trikalinos TA, Schmid CH, Huggins GS, Kent DM. Heterogeneity of the phenotypic definition of coronary artery disease and its impact on genetic association studies. Circ Cardiovasc Genet. 2011;4:58-67.
33. Patterson N, Hattangadi N, Lane B, Lohmueller KE, Hafler DA, Oksenberg JR, Hauser SL, Smith MW, O'Brien SJ, Altshuler D, Daly MJ, Reich D. Methods for high-density admixture mapping of disease genes. Am J Hum Genet. 2004;74:979-1000. (Pubitemid 38578397)
34. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177-188. (Pubitemid 17189972)
35. Ioannidis JP, Patsopoulos NA, Evangelou E. Heterogeneity in meta-analyses of genome-wide association investigations. PLoS ONE. 2007;2:e841.
36. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557-560. (Pubitemid 37088507)
37. Saleheen D, Alexander M, Rasheed A, Wormser D, Soranzo N, Hammond N, Butterworth A, Zaidi M, Haycock P, Bumpstead S, Potter S, Blackburn H, Gray E, Di Angelantonio E, Kaptoge S, Shah N, Samuel M, Janjua A, Sheikh N, Haider SR, Murtaza M, Ahmad U, Hakeem A, Memon MA, Mallick NH, Azhar M, Samad A, Rasheed SZ, Gardezi AR, Memon NA, Ghaffar A, Fazal Ur R, Zaman KS, Kundi A, Yaqoob Z, Cheema LA, Qamar N, Faruqui A, Jooma R, Niazi JH, Hussain M, Kumar K, Saleem A, Daood MS, Memon F, Gul AA, Abbas S, Zafar J, Shahid F, Memon Z, Bhatti SM, Kayani W, Ali SS, Fahim M, Ishaq M, Frossard P, Deloukas P, Danesh J. Association of the 9p21.3 locus with risk of first-ever myocardial infarction in Pakistanis: case-control study in South Asia and updated meta-analysis of Europeans. Arterioscler Thromb Vasc Biol. 2010;30:1467-1473.
38. Ding H, Xu Y, Wang X, Wang Q, Zhang L, Tu Y, Yan J, Wang W, Hui R, Wang CY, Wang DW. 9p21 is a shared susceptibility locus strongly for coronary artery disease and weakly for ischemic stroke in Chinese Han population. Circ Cardiovasc Genet. 2009;2:338-346.
39. Hiura Y, Fukushima Y, Yuno M, Sawamura H, Kokubo Y, Okamura T, Tomoike H, Goto Y, Nonogi H, Takahashi R, Iwai N. Validation of the association of genetic variants on chromosome 9p21 and 1q41 with myocardial infarction in a Japanese population. Circ J. 2008;72:1213-1217.
40. Hinohara K, Nakajima T, Takahashi M, Hohda S, Sasaoka T, Nakahara K, Chida K, Sawabe M, Arimura T, Sato A, Lee BS, Ban JM, Yasunami M, Park JE, Izumi T, Kimura A. Replication of the association between a chromosome 9p21 polymorphism and coronary artery disease in Japanese and Korean populations. J Hum Genet. 2008;53:357-359.
41. Harismendy O, Notani D, Song X, Rahim NG, Tanasa B, Heintzman N, Ren B, Fu XD, Topol EJ, Rosenfeld MG, Frazer KA. 9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response. Nature. 2011;470:264-268.
42. 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, Patel RS, Patterson CC, Peters A, Peyvandi F, Qu L, Quyyumi AA, Rader DJ, Rallidis LS, Rice C, Rosendaal FR, Rubin D, Salomaa V, Sampietro ML, Sandhu MS, Schadt E, Schafer A, Schillert A, Schreiber S, Schrezenmeir J, Schwartz SM, Siscovick DS, Sivananthan M, Sivapalaratnam S, Smith A, Smith TB, Snoep JD, Soranzo N, Spertus JA, Stark K, Stirrups K, Stoll M, Tang WH, Tennstedt S, Thorgeirsson G, Thorleifsson G, Tomaszewski M, Uitterlinden AG, van Rij AM, Voight BF, Wareham NJ, Wells GA, Wichmann HE, Wild PS, Willenborg C, Witteman JC, Wright BJ, Ye S, Zeller T, Ziegler A, Cambien F, Goodall AH, Cupples LA, Quertermous T, Marz W, Hengstenberg C, Blankenberg S, Ouwehand WH, Hall AS, Deloukas P, Thompson JR, Stefansson K, Roberts R, Thorsteinsdottir U, O'Donnell CJ, McPherson R, Erdmann J, Samani NJ. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011;43:333-338.
43. Ripatti S, Tikkanen E, Orho-Melander M, Havulinna AS, Silander K, Sharma A, Guiducci C, Perola M, Jula A, Sinisalo J, Lokki ML, Nieminen MS, Melander O, Salomaa V, Peltonen L, Kathiresan S. A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses. Lancet. 2010;376:1393-1400.
44. 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. 2010;466:714-719.