Advances in genomic analysis of stroke: What have we learned and where are we headed?

Stroke

Volumn 41, Issue 4, 2010, Pages 825-832

  Lanktree, Matthew B ^a   Dichgans, Martin ^b   Hegele, Robert A ^a  

^a WESTERN UNIVERSITY   (Canada)

^b LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

Author keywords

Atherosclerosis; Genetics; Intracranial aneurysm; Ischemia; Risk factors; Stroke

Indexed keywords

5 METHYLTETRAHYDROFOLIC ACID;

ATHEROSCLEROSIS; BASE PAIRING; BODY MASS; CADASIL; CEREBROVASCULAR ACCIDENT; CLINICAL MEDICINE; DNA MICROARRAY; EPISTASIS; GENE INTERACTION; GENE LOCUS; GENETIC ASSOCIATION; GENETIC HETEROGENEITY; GENETIC TRAIT; GENETIC VARIABILITY; GENOME ANALYSIS; HUMAN; HUMAN GENOME; IMAGE ANALYSIS; INTELLIGENCE; INTRACRANIAL ANEURYSM; KNOWLEDGE; MOLECULAR BIOLOGY; PHENOTYPE; PLEIOTROPY; PRINCIPAL COMPONENT ANALYSIS; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM; STROKE;

DATABASES, GENETIC; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; GENOME, HUMAN; GENOME-WIDE ASSOCIATION STUDY; GENOMICS; GENOTYPE; HUMANS; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; RESEARCH DESIGN; STROKE;

EID: 77950221224     PISSN: 00392499     EISSN: None     Source Type: Journal    
DOI: 10.1161/STROKEAHA.109.570523     Document Type: Review

References (54)

1. Dichgans M. Genetics of ischaemic stroke. Lancet Neurol. 2007;6: 149-161.
2. Hardy J, Singleton A. Genomewide association studies and human disease. N Engl J Med. 2009;360:1759-1768.
3. Pearson TA, Manolio TA. How to interpret a genome-wide association study. JAMA. 2008;299:1335-1344.
4. Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L, McGuire A, He W, Chen YJ, Makhijani V, Roth GT, Gomes X, Tartaro K, Niazi F, Turcotte CL, Irzyk GP, Lupski JR, Chinault C, Song XZ, Liu Y, Yuan Y, Nazareth L, Qin X, Muzny DM, Margulies M, Weinstock GM, Gibbs RA, Rothberg JM. The complete genome of an individual by massively parallel DNA sequencing. Nature. 2008;452:872-876.
5. Barrett JC, Cardon LR. Evaluating coverage of genome-wide association studies. Nat Genet. 2006;38:659-662.
6. McCarroll SA, Kuruvilla FG, Korn JM, Cawley S, Nemesh J, Wysoker A, Shapero MH, de Bakker PI, Maller JB, Kirby A, Elliott AL, Parkin M, Hubbell E, Webster T, Mei R, Veitch J, Collins PJ, Handsaker R, Lincoln S, Nizzari M, Blume J, Jones KW, Rava R, Daly MJ, Gabriel SB, Altshuler D. Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat Genet. 2008;40:1166-1174.
7. Conrad DF, Pinto D, Redon R, Feuk L, Gokcumen O, Zhang Y, Aerts J, Andrews TD, Barnes C, Campbell P, Fitzgerald T, Hu M, Ihm CH, Kristiansson K, Macarthur DG, Macdonald JR, Onyiah I, Pang AW, Robson S, Stirrups K, Valsesia A, Walter K, Wei J, Tyler-Smith C, Carter NP, Lee C, Scherer SW, Hurles ME. Origins and functional impact of copy number variation in the human genome. Nature. 2009. October 7. Epub ahead of print.
8. McCarroll SA, Huett A, Kuballa P, Chilewski SD, Landry A, Goyette P, Zody MC, Hall JL, Brant SR, Cho JH, Duerr RH, Silverberg MS, Taylor KD, Rioux JD, Altshuler D, Daly MJ, Xavier RJ. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease. Nat Genet. 2008;40:1107-1112.
9. Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, Berndt SI, Elliott AL, Jackson AU, Lamina C, Lettre G, Lim N, Lyon HN, McCarroll SA, Papadakis K, Qi L, Randall JC, Roccasecca RM, Sanna S, Scheet P, Weedon MN, Wheeler E, Zhao JH, Jacobs LC, Prokopenko I, Soranzo N, Tanaka T, Timpson NJ, Almgren P, Bennett A, Bergman RN, Bingham SA, Bonnycastle LL, Brown M, Burtt NP, Chines P, Coin L, Collins FS, Connell JM, Cooper C, Smith GD, Dennison EM, Deodhar P, Elliott P, Erdos MR, Estrada K, Evans DM, Gianniny L, Gieger C, Gillson CJ, Guiducci C, Hackett R, Hadley D, Hall AS, Havulinna AS, Hebebrand J, Hofman A, Isomaa B, Jacobs KB, Johnson T, Jousilahti P, Jovanovic Z, Khaw KT, Kraft P, Kuokkanen M, Kuusisto J, Laitinen J, Lakatta EG, Luan J, Luben RN, Mangino M, McArdle WL, Meitinger T, Mulas A, Munroe PB, Narisu N, Ness AR, Northstone K, O'Rahilly S, Purmann C, Rees MG, Ridderstrale M, Ring SM, Rivadeneira F, Ruokonen A, Sandhu MS, Saramies J, Scott LJ, Scuteri A, Silander K, Sims MA, Song K, Stephens J, Stevens S, Stringham HM, Tung YC, Valle TT, Van Duijn CM, Vimaleswaran KS, Vollenweider P, Waeber G, Wallace C, Watanabe RM, Waterworth DM, Watkins N, Witteman JC, Zeggini E, Zhai G, Zillikens MC, Altshuler D, Caulfield MJ, Chanock SJ, Farooqi IS, Ferrucci L, Guralnik JM, Hattersley AT, Hu FB, Jarvelin MR, Laakso M, Mooser V, Ong KK, Ouwehand WH, Salomaa V, Samani NJ, Spector TD, Tuomi T, Tuomilehto J, Uda M, Uitterlinden AG, Wareham NJ, Deloukas P, Frayling TM, Groop LC, Hayes RB, Hunter DJ, Mohlke KL, Peltonen L, Schlessinger D, Strachan DP, Wichmann HE, McCarthy MI, Boehnke M, Barroso I, Abecasis GR, Hirschhorn JN. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet. 2009;41:25-34.
10. Matarin M, Simon-Sanchez J, Fung HC, Scholz S, Gibbs JR, Hernandez DG, Crews C, Britton A, De Vrieze FW, Brott TG, Brown RD Jr, Worrall BB, Silliman S, Case LD, Hardy JA, Rich SS, Meschia JF, Singleton AB. Structural genomic variation in ischemic stroke. Neurogenetics. 2008;9: 101-108.
11. Meschia JF. Pharmacogenetics and stroke. Stroke. 2009;40:3641-3645.
12. Balding DJ. A tutorial on statistical methods for population association studies. Nat Rev Genet. 2006;7:781-791.
13. Torkamani A, Schork NJ. Pathway and network analysis with high-density allelic association data. Methods Mol Biol. 2009;563:289-301.
14. Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG. Cadasil. Lancet Neurol. 2009;8:643-653.
15. Teo YY, Inouye M, Small KS, Gwilliam R, Deloukas P, Kwiatkowski DP, Clark TG. A genotype calling algorithm for the illumina bead array platform. Bioinformatics. 2007;23:2741-2746.
16. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC. Plink: A tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559-575.
17. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D.Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006;38:904-909.
18. Devlin B, Roeder K, Wasserman L. Genomic control, a new approach to genetic-based association studies. Theor Popul Biol. 2001;60:155-166.
19. Ariyaratnam R, Casas JP, Whittaker J, Smeeth L, Hingorani AD, Sharma P. Genetics of ischaemic stroke among persons of non-European descent: A meta-analysis of eight genes involving approximately 32,500 individuals. PLoS Med. 2007;4:e131.
20. Casas JP, Hingorani AD, Bautista LE, Sharma P. Meta-analysis of genetic studies in ischemic stroke: Thirty-two genes involving approximately 18,000 cases and 58,000 controls. Arch Neurol. 2004;61:1652-1661.
21. Matarin M, Brown WM, Dena H, Britton A, De Vrieze FW, Brott TG, Brown RD Jr, Worrall BB, Case LD, Chanock SJ, Metter EJ, Ferruci L, Gamble D, Hardy JA, Rich SS, Singleton A, Meschia JF. Candidate gene polymorphisms for ischemic stroke. Stroke. 2009;40:3436-3442.
22. Bilguvar K, Yasuno K, Niemela M, Ruigrok YM, von Und Zu Fraunberg M, van Duijn CM, van den Berg LH, Mane S, Mason CE, Choi M, Gaal E,Bayri Y, Kolb L, Arlier Z, Ravuri S, Ronkainen A, Tajima A, Laakso A, Hata A, Kasuya H, Koivisto T, Rinne J, Ohman J, Breteler MM, Wijmenga C, State MW, Rinkel GJ, Hernesniemi J, Jaaskelainen JE, Palotie A, Inoue I, Lifton RP, Gunel M. Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nat Genet. 2008;40: 1472-1477.
23. Gretarsdottir S, Thorleifsson G, Manolescu A, Styrkarsdottir U, Helga-dottir A, Gschwendtner A, Kostulas K, Kuhlenbaumer G, Bevan S, Jonsdottir T, Bjarnason H, Saemundsdottir J, Palsson S, Arnar DO, Holm H, Thorgeirsson G, Valdimarsson EM, Sveinbjornsdottir S, Gieger C, Berger K, Wichmann HE, Hillert J, Markus H, Gulcher JR, Ringelstein EB, Kong A, Dichgans M, Gudbjartsson DF, Thorsteinsdottir U, Ste-fansson K. Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke. Ann Neurol. 2008;64:402-409.
24. Gudbjartsson DF, Holm H, Gretarsdottir S, Thorleifsson G, Walters GB, Thorgeirsson G, Gulcher J, Mathiesen EB, Njolstad I, Nyrnes A, Wilsgaard T, Hald EM, Hveem K, Stoltenberg C, Kucera G, Stubblefield T, Carter S, Roden D, Ng MC, Baum L, So WY, Wong KS, Chan JC, Gieger C, Wichmann HE, Gschwendtner A, Dichgans M, Kuhlenbaumer G, Berger K, Ringelstein EB, Bevan S, Markus HS, Kostulas K, Hillert J, Sveinbjornsdottir S, Valdimarsson EM, Lochen ML, Ma RC, Darbar D, Kong A, Arnar DO, Thorsteinsdottir U, Stefansson K. A sequence variant in zfhx3 on 16q22 associates with atrial fibrillation and ischemic stroke. Nat Genet. 2009;41:876-878.
25. Hata J, Matsuda K, Ninomiya T, Yonemoto K, Matsushita T, Ohnishi Y, Saito S, Kitazono T, Ibayashi S, Iida M, Kiyohara Y, Nakamura Y, Kubo M. Functional snp in an sp1-binding site of agtrl1 gene is associated with susceptibility to brain infarction. Hum Mol Genet. 2007;16:630-639.
26. Ikram MA, Seshadri S, Bis JC, Fornage M, DeStefano AL, Aulchenko YS, Debette S, Lumley T, Folsom AR, van den Herik EG, Bos MJ, Beiser A, Cushman M, Launer LJ, Shahar E, Struchalin M, Du Y, Glazer NL, Rosamond WD, Rivadeneira F, Kelly-Hayes M, Lopez OL, Coresh J, Hofman A, DeCarli C, Heckbert SR, Koudstaal PJ, Yang Q, Smith NL, Kase CS, Rice K, Haritunians T, Roks G, de Kort PL, Taylor KD, de Lau LM, Oostra BA, Uitterlinden AG, Rotter JI, Boerwinkle E, Psaty BM, Mosley TH, van Duijn CM, Breteler MM, Longstreth WT Jr, Wolf PA. Genomewide association studies of stroke. N Engl J Med. 2009;360: 1718-1728.
27. Kubo M, Hata J, Ninomiya T, Matsuda K, Yonemoto K, Nakano T, Matsushita T, Yamazaki K, Ohnishi Y, Saito S, Kitazono T, Ibayashi S, Sueishi K, Iida M, Nakamura Y, Kiyohara Y. A nonsynonymous snp in prkch (protein kinase c eta) increases the risk of cerebral infarction. Nat Genet. 2007;39:212-217.
28. Matarin M, Brown WM, Scholz S, Simon-Sanchez J, Fung HC, Hernandez D, Gibbs JR, De Vrieze FW, Crews C, Britton A, Langefeld CD, Brott TG, Brown RD Jr, Worrall BB, Frankel M, Silliman S, Case LD, Singleton A, Hardy JA, Rich SS, Meschia JF. A genome-wide genotyping study in patients with ischaemic stroke: Initial analysis and data release. Lancet Neurol. 2007;6:414-420.
29. Yamada Y, Fuku N, Tanaka M, Aoyagi Y, Sawabe M, Metoki N, Yoshida H, Satoh K, Kato K, Watanabe S, Nozawa Y, Hasegawa A, Kojima T. Identification of celsr1 as a susceptibility gene for ischemic stroke in japanese individuals by a genome-wide association study. Atherosclerosis. 2009;207: 144-149.
30. 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;40:217-224.
31. Gschwendtner A, Bevan S, Cole JW, Plourde A, Matarin M, Ross-Adams H, Meitinger T, Wichmann E, Mitchell BD, Furie K, Slowik A, Rich SS, Syme PD, MacLeod MJ, Meschia JF, Rosand J, Kittner SJ, Markus HS, Muller-Myhsok B, Dichgans M. Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. Ann Neurol. 2009;65: 531-539.
32. 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.
33. Lemmens R, Abboud S, Robberecht W, Vanhees L, Pandolfo M, Thijs V, Goris A. Variant on 9p21 strongly associates with coronary heart disease, but lacks association with common stroke. Eur J Hum Genet. 2009;17: 1287-1293.
34. Wahlstrand B, Orho-Melander M, Delling L, Kjeldsen S, Narkiewicz K, Almgren P, Hedner T, Melander O. The myocardial infarction associated cdkn2a/cdkn2b locus on chromosome 9p21 is associated with stroke independently of coronary events in patients with hypertension. J Hypertens. 2009;27:769-773.
35. Lanktree MB, Anand SS, Yusuf S, Hegele RA. Replication of genetic associations with plasma lipoprotein traits in a multiethnic sample. J Lipid Res. 2009;50:1487-1496.
36. Hegele RA. Plasma lipoproteins: Genetic influences and clinical implications. Nat Rev Genet. 2009;10:109-121.
37. 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, Seedorf U, Syvanen AC, Tognoni G, Lakatta EG, Sanna S, Scheet P, Schlessinger D, Scuteri A, Dorr M, Ernst F,Felix SB, Homuth G, Lorbeer R, Reffelmann T, Rettig R, Volker U, Galan P, Gut IG, Hercberg S, Lathrop GM, Zelenika D, Deloukas P, Soranzo N, Williams FM, Zhai G, Salomaa V, Laakso M, Elosua R, Forouhi NG, Volzke H, Uiterwaal CS, van der Schouw YT, Numans ME, Matullo G, Navis G, Berglund G, Bingham SA, Kooner JS, Connell JM, Bandinelli S, Ferrucci L, Watkins H, Spector TD, Tuomilehto J, Altshuler D, Strachan DP, Laan M, Meneton P, Wareham NJ, Uda M, Jarvelin MR, Mooser V, Melander O, Loos RJ, Elliott P, Abecasis GR, Caulfield M, Munroe PB. Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet. 2009. May 10. Epub ahead of print.
38. 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. May 10. Epub ahead of print.
39. Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, Styrkarsdottir U, Gretarsdottir S, Thorlacius S, Jonsdottir I, Jonsdottir T, Olafsdottir EJ, Olafsdottir GH, Jonsson T, Jonsson F, Borch-Johnsen K, Hansen T, Andersen G, Jorgensen T, Lau-ritzen T, Aben KK, Verbeek AL, Roeleveld N, Kampman E, Yanek LR, Becker LC, Tryggvadottir L, Rafnar T, Becker DM, Gulcher J, Kiemeney LA, Pedersen O, Kong A, Thorsteinsdottir U, Stefansson K. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet. 2009;41:18-24.
40. Stolerman ES, Florez JC. Genomics of type 2 diabetes mellitus: Implications for the clinician. Nat Rev Endocrinol. 2009;5:429-436.
41. Jensen MB, Chacon MR, Sattin JA, Levine RL, Vemuganti R. Potential biomarkers for the diagnosis of stroke. Expert Rev Cardiovasc Ther. 2009;7:389-393.
42. Seshadri S, DeStefano AL, Au R, Massaro JM, Beiser AS, Kelly-Hayes M, Kase CS, D'Agostino RB Sr, Decarli C, Atwood LD, Wolf PA. Genetic correlates of brain aging on mri and cognitive test measures: A genome-wide association and linkage analysis in the Framingham study. BMC Med Genet. 2007;8(Suppl 1):S15.
43. Lanktree MB, Hegele RA, Yusuf S, Anand SS. Multi-ethnic genetic association study of carotid intima-media thickness using a targeted cardiovascular SNP microarray. Stroke. 2009;40:3173-3179.
44. Sheehan NA, Didelez V, Burton PR, Tobin MD. Mendelian randomisation and causal inference in observational epidemiology. PLoS Med. 2008;5:e177.
45. Casas JP, Bautista LE, Smeeth L, Sharma P, Hingorani AD. Homo-cysteine and stroke: Evidence on a causal link from mendelian randomisation. Lancet. 2005;365:224-232.
46. Hegele RA. SNP judgments and freedom of association. Arterioscler Thromb Vasc Biol. 2002;22:1058-1061.
47. Spencer CC, Su Z, Donnelly P, Marchini J. Designing genome-wide association studies: Sample size, power, imputation, and the choice of genotyping chip. PLoS Genet. 2009;5:e1000477.
48. Marchini J, Howie B, Myers S, McVean G, Donnelly P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet. 2007;39:906-913.
49. Pereira TV, Patsopoulos NA, Salanti G, Ioannidis JP. Discovery properties of genome-wide association signals from cumulatively combined data sets. Am J Epidemiol. 2009;170:1197-1206.
50. Freimer N, Sabatti C. The human phenome project. Nat Genet. 2003;34: 15-21.
51. Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Hennerici MG. New approach to stroke subtyping: The a-s-c-o (phenotypic) classification of stroke. Cerebrovasc Dis. 2009;27:502-508.
52. Lussier YA, Liu Y. Computational approaches to phenotyping: High-throughput phenomics. Proc Am Thorac Soc. 2007;4:18-25.
53. Cohen JC, Kiss RS, Pertsemlidis A, Marcel YL, McPherson R, Hobbs HH. Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science. 2004;305:869-872.
54. Wang J, Cao H, Ban MR, Kennedy BA, Zhu S, Anand S, Yusuf S, Pollex RL, Hegele RA. Resequencing genomic DNA of patients with severe hypertriglyceridemia (mim 144650). Arterioscler Thromb Vasc Biol. 2007;27:2450-2455.