Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction

Nature

Volumn 518, Issue 7537, 2015, Pages 102-106

  Do, Ron ^a,b,c   Stitziel, Nathan O ^d   Won, Hong Hee ^a,b,c   Jørgensen, Anders Berg ^e   Duga, Stefano ^f   Merlini, Pier Angelica ^g   Kiezun, Adam ^c   Farrall, Martin ^h   Goel, Anuj ^h   Zuk, Or ^c   Guella, Illaria ^f   Asselta, Rosanna ^f   Lange, Leslie A ⁱ   Peloso, Gina M ^a,b,c   Auer, Paul L ^j   Girelli, Domenico ^k   Martinelli, Nicola ^k   Farlow, Deborah N ^c   DePristo, Mark A ^c   Roberts, Robert ^l   Stewart, Alexander F R ^l   Saleheen, Danish ^m   Danesh, John ^m   Epstein, Stephen E ⁿ   Sivapalaratnam, Suthesh ^o   Hovingh, G Kees ^o   Kastelein, John J ^o   Samani, Nilesh J ^p   Schunkert, Heribert ^q   Erdmann, Jeanette ^r   Shah, Svati H ^s   Kraus, William E ^s   Davies, Robert ^l   Nikpay, Majid ^l   Johansen, Christopher T ^t   Wang, Jian ^t   Hegele, Robert A ^t   Hechter, Eliana ^c   Marz, Winfried ^u,v,w   Kleber, Marcus E ^u   Huang, Jie ^x   Johnson, Andrew D ^x   Li, Mingyao ^y   Burke, Greg L ^z   Gross, Myron ^aa   Liu, Yongmei ^ab   Assimes, Themistocles L ^ac   Heiss, Gerardo ^ad   Lange, Ethan M ^i,ae   Folsom, Aaron R ^af   Taylor, Herman A ^ag   Olivieri, Oliviero ^k   Hamsten, Anders ^ah   Clarke, Robert ^ai   Reilly, Dermot F ^aj   Yin, Wu ^aj   Rivas, Manuel A ^h   Donnelly, Peter ^h,ai   Rossouw, Jacques E ^ak   Psaty, Bruce M ^al,am   Herrington, David M ^ab   Wilson, James G ^ag   Rich, Stephen S ^an   Bamshad, Michael J ^al,ao,ap   Tracy, Russell P ^aq   Cupples, L Adrienne ^ar   Rader, Daniel J ^y   Reilly, Muredach P ^y   Spertus, John A ^as   Cresci, Sharon ^d   Hartiala, Jaana ^at   Tang, W H Wilson ^au   Hazen, Stanley L ^au   Allayee, Hooman ^at   Reiner, Alex P ^j,ap   Carlson, Christopher S ^j   Kooperberg, Charles ^j   Jackson, Rebecca D ^av   Boerwinkle, Eric ^aw   Lander, Eric S ^c   Schwartz, Stephen M ^j,ap   Siscovick, David S ^al,ap   McPherson, Ruth ^l   Tybjaerg Hansen, Anne ^e,ax   Abecasis, Goncalo R ^ay   Watkins, Hugh ^h   Nickerson, Deborah A ^ap   Ardissino, Diego ^az   Sunyaev, Shamil R ^b,c   O'Donnell, Christopher J ^x   Altshuler, David ^a,c   Gabriel, Stacey ^c   Kathiresan, Sekar ^a,b,c   more..

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^d WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF COPENHAGEN   (Denmark)

^f UNIVERSITY OF MILAN   (Italy)

^g OSPEDALE NIGUARDA CA GRANDA   (Italy)

^h UNIVERSITY OF OXFORD   (United Kingdom)

ⁱ UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^j Fred Hutchinson Cancer Research Center   (United States)

^k UNIVERSITY OF VERONA   (Italy)

^l UNIVERSITY OF OTTAWA HEART INSTITUTE   (Canada)

^m UNIVERSITY OF CAMBRIDGE   (United Kingdom)

ⁿ MEDSTAR RESEARCH INSTITUTE   (United States)

^o ACADEMIC MEDICAL CENTER   (Netherlands)

^p UNIVERSITY OF LEICESTER   (United Kingdom)

^q TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^r UNIVERSITY OF LÜBECK   (Germany)

^s DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^t WESTERN UNIVERSITY   (Canada)

^u MEDICAL FACULTY MANNHEIM HEIDELBERG UNIVERSITY   (Germany)

^v MEDICAL UNIVERSITY OF GRAZ   (Austria)

^w SYNLAB ACADEMY   (Germany)

^x FRAMINGHAM HEART STUDY   (United States)

^y UNIVERSITY OF PENNSYLVANIA   (United States)

^z UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^aa UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^ab WAKE FOREST SCHOOL OF MEDICINE   (United States)

^ac STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

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

^ae UNIVERSITY OF NORTH CAROLINA   (United States)

^af UNIVERSITY OF MINNESOTA   (United States)

^ag UNIVERSITY OF MISSISSIPPI MEDICAL CENTER   (United States)

^ah KAROLINSKA INSTITUTE   (Sweden)

^ai UNIVERSITY OF OXFORD   (United Kingdom)

^aj MERCK RESEARCH LABORATORIES   (United States)

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

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

^am CENTER FOR HEALTH STUDIES   (United States)

^an UNIVERSITY OF VIRGINIA   (United States)

^ao SEATTLE CHILDREN S HOSPITAL   (United States)

^ap UNIVERSITY OF WASHINGTON   (United States)

^aq UNIVERSITY OF VERMONT   (United States)

^ar BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH   (United States)

^as UNIVERSITY OF MISSOURI KANSAS CITY   (United States)

^at UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^au LERNER RESEARCH INSTITUTE   (United States)

^av OHIO STATE UNIVERSITY   (United States)

^aw UNIVERSITY OF TEXAS   (United States)

^ax UNIVERSITY OF COPENHAGEN   (Denmark)

^ay UNIVERSITY OF MICHIGAN SCHOOL OF PUBLIC HEALTH   (United States)

^az Parma Hospital   (Italy)

more..

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN A5; APOLIPOPROTEIN C3; LIPOPROTEIN LIPASE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN RECEPTOR; TRIACYLGLYCEROL; APOA5 PROTEIN, HUMAN; APOLIPOPROTEIN A;

ALLELE; CARDIOVASCULAR DISEASE;

ADULT; ARTICLE; CARDIOVASCULAR RISK; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; CORONARY ARTERY DISEASE; EXOME; FEMALE; GENE FREQUENCY; GENE MUTATION; GENE SEQUENCE; HEART INFARCTION; HETEROZYGOTE; HUMAN; MAJOR CLINICAL STUDY; MALE; NULL ALLELE; PRIORITY JOURNAL; TRIACYLGLYCEROL BLOOD LEVEL; AGE; ALLELE; BLOOD; CASE CONTROL STUDY; GENETIC PREDISPOSITION; GENETICS; MIDDLE AGED; MUTATION; NATIONAL HEALTH ORGANIZATION; ONSET AGE; POPULATION GENETICS; UNITED STATES;

AGE FACTORS; AGE OF ONSET; ALLELES; APOLIPOPROTEINS A; CASE-CONTROL STUDIES; CHOLESTEROL, LDL; CORONARY ARTERY DISEASE; EXOME; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENETICS, POPULATION; HETEROZYGOTE; HUMANS; MALE; MIDDLE AGED; MUTATION; MYOCARDIAL INFARCTION; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE (U.S.); RECEPTORS, LDL; TRIGLYCERIDES; UNITED STATES;

EID: 84923082408     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature13917     Document Type: Article

References (48)

1. Marenberg, M. E., Risch, N., Berkman, L. F., Floderus, B. & de Faire, U. Genetic susceptibility to death from coronary heart disease in a study of twins. N. Engl. J. Med. 330, 1041-1046 (1994).
2. Lloyd-Jones, D. M. et al. Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring. J. Am. Med. Assoc. 291, 2204-2211 (2004).
3. Lehrman, M. A. et al. Mutation in LDL receptor: Alu-Alu recombination deletes exons encoding transmembrane and cytoplasmic domains. Science 227, 140-146 (1985).
4. Brown, M. S. & Goldstein, J. L. A receptor-mediated pathway for cholesterol homeostasis. Science 232, 34-47 (1986).
5. Soria, L.F. et al. Associationbetweena specific apolipoproteinBmutationandfamilial defective apolipoprotein B-100. Proc. Natl Acad. Sci. USA 86, 587-591 (1989).
6. Garcia, C. K. et al. Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. Science 292, 1394-1398 (2001).
7. Berge, K. E. et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290, 1771-1775 (2000).
8. Abifadel, M. et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nature Genet. 34, 154-156 (2003).
9. McPherson, R. et al. A common allele on chromosome 9 associated with coronary heart disease. Science 316, 1488-1491 (2007).
10. Samani, N. J. et al. Genomewide association analysis of coronary artery disease. N. Engl. J. Med. 357, 443-453 (2007).
11. Helgadottir, A. et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 316, 1491-1493 (2007).
12. Kathiresan, S. et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nature Genet. 41, 334-341 (2009).
13. Schunkert, H. et al.Large-scale associationanalysis identifies13newsusceptibility loci for coronary artery disease. Nature Genet. 43, 333-338 (2011).
14. Coronary Artery Disease (C4D) Genetics Consortium. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nature Genet. 43, 339-344 (2011).
15. The CARDIoGRAMplusC4D Consortium et al. Large-scale association analysis identifiesnewrisk loci for coronary artery disease. NatureGenet.45, 25-33(2013).
16. Goldstein, J. L., Schrott, H. G., Hazzard, W. R., Bierman, E. L. & Motulsky, A. G. Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. J. Clin. Invest. 52, 1544-1568 (1973).
17. Varbo, A. et al. Remnant cholesterol as a causal risk factor for ischemic heart disease. J. Am. Coll. Cardiol. 61, 427-436 (2013).
18. The TG andHDLWorking Group of the Exome Sequencing Project, National Heart, Lung and Blood Institute et al. Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N. Engl. J. Med. 371, 22-31 (2014).
19. Jørgensen, A. B., Frikke-Schmidt, R., Nordestgaard, B. G. & Tybjaerg-Hansen, A. Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N. Engl. J. Med. 371, 32-41 (2014).
20. Gnirke, A. et al. Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing. Nature Biotechnol. 27, 182-189 (2009).
21. Li, B. & Leal, S. M. Methods for detecting associations with rare variants for commondiseases: application toanalysis of sequence data.Am. J.Hum. Genet. 83, 311-321 (2008).
22. Purcell, S. M. et al. A polygenic burden of rare disruptive mutations in schizophrenia. Nature 506, 185-190 (2014).
23. Leigh, S. E., Foster, A. H., Whittall, R. A., Hubbart, C. S.&Humphries, S. E.Update and analysis of the University College London low density lipoprotein receptor familial hypercholesterolemia database. Ann. Hum. Genet. 72, 485-498 (2008).
24. Pennacchio, L. A. et al. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294, 169-173 (2001).
25. Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration et al. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet 375, 1634-1639 (2010).
26. Teslovich, T. M. et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466, 707-713 (2010).
27. Do, R. et al. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nature Genet. 45, 1345-1352 (2013).
28. Pollin, T. I. et al. A nullmutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science 322, 1702-1705 (2008).
29. Tennessen, J. A. et al. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 337, 64-69 (2012).
30. Antman, E. et al. Myocardial infarction redefined - a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J. Am. Coll. Cardiol. 36, 959-969 (2000).
31. Fisher, S. et al. A scalable, fully automated process for construction of sequenceready human exome targeted capture libraries. Genome Biol. 12, R1 (2011).
32. Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754-1760 (2009).
33. DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nature Genet. 43, 491-498 (2011).
34. Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078-2079 (2009).
35. Cingolani, P. et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w (1118); iso-2; iso-3. Fly 6, 80-92 (2012).
36. Willer, C. J., Li, Y. & Abecasis, G. R. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190-2191 (2010).
37. Sunyaev, S. et al. Prediction of deleterious human alleles. Hum. Mol. Genet. 10, 591-597 (2001).
38. 1000Genomes ProjectsConsortiumet al.Amapofhuman genome variation from population-scale sequencing. Nature 467, 1061-1073 (2010).
39. Howie, B. N., Donnelly, P. & Marchini, J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 5, e1000529 (2009).
40. Marchini, J., Howie, B., Myers, S., McVean, G. & Donnelly, P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nature Genet. 39, 906-913 (2007).
41. Price, A. L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nature Genet. 38, 904-909 (2006).
42. Purcell, S. et al. PLINK: a tool set for whole-genome association and populationbased linkage analyses. Am. J. Hum. Genet. 81, 559-575 (2007).
43. Stephens, M., Sloan, J. S., Robertson, P. D., Scheet, P.&Nickerson, D. A. Automating sequence-based detection and genotyping of SNPs fromdiploid samples. Nature Genet. 38, 375-381 (2006).
44. Gordon, D., Abajian, C. & Green, P. Consed: a graphical tool for sequence finishing. Genome Res. 8, 195-202 (1998).
45. Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).
46. Jun, G. et al. Detecting and estimating contamination of human DNA samples in sequencing and array-based genotype data. Am. J. Hum. Genet. 91, 839-848 (2012).
47. Kang, H. M. et al. Variance component model to account for sample structure in genome-wide association studies. Nature Genet. 42, 348-354 (2010).
48. Kryukov, G. V., Shpunt, A., Stamatoyannopoulos, J. A. & Sunyaev, S. R. Power of deep, all-exon resequencing for discovery of human trait genes. Proc. Natl Acad. Sci. USA 106, 3871-3876 (2009).