A common variant on chromosome 9p21 affects the risk of myocardial infarction.
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- Authors
- Helgadottir, Anna; Thorleifsson, Gudmar; Manolescu, Andrei; Gretarsdottir, Solveig; Blondal, Thorarinn; Jonasdottir, Aslaug; Jonasdottir, Adalbjorg; Sigurdsson, Asgeir; Baker, Adam; Palsson, Arnar; Masson, Gisli; Gudbjartsson, Daniel F; Magnusson, Kristinn P; Andersen, Karl; Levey, Allan I; Backman, Valgerdur M; Matthiasdottir, Sigurborg; Jonsdottir, Thorbjorg; Palsson, Stefan; Einarsdottir, Helga; Gunnarsdottir, Steinunn; Gylfason, Arnaldur; Vaccarino, Viola; Hooper, W Craig; Reilly, Muredach P; Granger, Christopher B; Austin, Harland; Rader, Daniel J; Shah, Svati H; Quyyumi, Arshed A; Gulcher, Jeffrey R; Thorgeirsson, Gudmundur; Thorsteinsdottir, Unnur; Kong, Augustine; Stefansson, Kari
- Year
- 2007
- Journal
- Science (New York, N.Y.)
- PMID
- 17478679
- DOI
- 10.1126/science.1142842
The global endemic of cardiovascular diseases calls for improved risk assessment and treatment. Here, we describe an association between myocardial infarction (MI) and a common sequence variant on chromosome 9p21. This study included a total of 4587 cases and 12,767 controls. The identified variant, adjacent to the tumor suppressor genes CDKN2A and CDKN2B, was associated with the disease with high significance. Approximately 21% of individuals in the population are homozygous for this variant, and their estimated risk of suffering myocardial infarction is 1.64 times as great as that of noncarriers. The corresponding risk is 2.02 times as great for early-onset cases. The population attributable risk is 21% for MI in general and 31% for early-onset cases.
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| Identification of a specific intronic PEAR1 gene variant associated with greater platelet aggregability and protein expression. | Faraday N et al. | — | 2011 | → |
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| Jeremiah Metzger Lecture: cholesterol, inflammation and atherosclerotic cardiovascular disease: is it all LDL? | Gotto AM | — | 2011 | → |
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| Novel associations for coronary artery disease derived from genome wide association studies are not associated with increased carotid intima-media thickness, suggesting they do not act via early atherosclerosis or vessel remodeling. | Conde L et al. | — | 2011 | → |
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| Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease. | Minear MA et al. | — | 2011 | → |
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| Prospective study of insulin-like growth factor-I, insulin-like growth factor-binding protein 3, genetic variants in the IGF1 and IGFBP3 genes and risk of coronary artery disease. | Ricketts SL et al. | — | 2011 | → |
| Protein interaction-based genome-wide analysis of incident coronary heart disease. | Jensen MK et al. | — | 2011 | → |
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| Association of three polymorphisms selected from a genome-wide association study with coronary heart disease in the Tunisian population. | Ghazouani L et al. | — | 2010 | → |
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| Common genetic variants on chromosome 9p21 are associated with myocardial infarction and type 2 diabetes in an Italian population. | Gori F et al. | — | 2010 | → |
| Common genetic variants on chromosome 9p21 predict perioperative myocardial injury after coronary artery bypass graft surgery. | Liu KY et al. | — | 2010 | → |
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| Genome-wide association studies in myocardial infarction and coronary artery disease. | Mannucci PM et al. | — | 2010 | → |
| Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm. | Gretarsdottir S et al. | — | 2010 | → |
| Genome-wide association study of coronary artery disease. | Ogawa N et al. | — | 2010 | → |
| Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus. | Bell CG et al. | — | 2010 | → |
| Genome-wide pleiotropy of osteoporosis-related phenotypes: the Framingham Study. | Karasik D et al. | — | 2010 | → |
| Genomic approaches to coronary artery disease. | Padmanabhan S et al. | — | 2010 | → |
| Genomics in coronary artery disease: past, present and future. | Dandona S et al. | — | 2010 | → |
| Genomics of premature atherosclerotic vascular disease. | Seo D et al. | — | 2010 | → |
| Genotype-based risk and pharmacogenetic sampling in clinical trials. | Schork NJ et al. | — | 2010 | → |
| High-throughput sequencing of microdissected chromosomal regions. | Weise A et al. | — | 2010 | → |
| Histone chaperone Jun dimerization protein 2 (JDP2): role in cellular senescence and aging. | Huang YC et al. | — | 2010 | → |
| Improved prediction of cardiovascular disease based on a panel of single nucleotide polymorphisms identified through genome-wide association studies. | Davies RW et al. | — | 2010 | → |
| Kalirin: a novel genetic risk factor for ischemic stroke. | Krug T et al. | — | 2010 | → |
| Lack of association between the Trp719Arg polymorphism in kinesin-like protein-6 and coronary artery disease in 19 case-control studies. | Assimes TL et al. | — | 2010 | → |
| Life-time risk factors and progression of carotid atherosclerosis in young adults: the Cardiovascular Risk in Young Finns study. | Juonala M et al. | — | 2010 | → |
| Longitudinal study of a 9p21.3 SNP using a national electronic healthcare database. | Gladding P et al. | — | 2010 | → |
| Maximal conditional chi-square importance in random forests. | Wang M et al. | — | 2010 | → |
| Monocyte chemoattractant protein-1-2518 G/A polymorphism, plasma levels, and premature stable coronary artery disease. | Zhong C et al. | — | 2010 | → |
| p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis. | González-Navarro H et al. | — | 2010 | → |
| Personalized genomic information: preparing for the future of genetic medicine. | Guttmacher AE et al. | — | 2010 | → |
| Pharmacogenomics--10 years of progress: a cardiovascular perspective. | Winkelmann BR et al. | — | 2010 | → |
| Preliminary evidence of a genetic association between chromosome 9p21.3 and human longevity. | Emanuele E et al. | — | 2010 | → |
| Recent advances in the genetics and genomics of asthma and related traits. | Sleiman PM et al. | — | 2010 | → |
| Reclassification of cardiovascular risk using integrated clinical and molecular biosignatures: Design of and rationale for the Measurement to Understand the Reclassification of Disease of Cabarrus and Kannapolis (MURDOCK) Horizon 1 Cardiovascular Disease Study. | Shah SH et al. | — | 2010 | → |
| Replication of the association of chromosomal region 9p21.3 with generalized aggressive periodontitis (gAgP) using an independent case-control cohort. | Ernst FD et al. | — | 2010 | → |
| Role of genomics in cardiovascular medicine. | Novelli G et al. | — | 2010 | → |
| Sex differential genetic effect of chromosome 9p21 on subclinical atherosclerosis. | Lin HF et al. | — | 2010 | → |
| Single nucleotide polymorphism on chromosome 9p21 and endothelial progenitor cells in a general population cohort. | Ye S et al. | — | 2010 | → |
| Single nucleotide polymorphism rs1333049 on chromosome 9p21.3 is associated with Alzheimer's disease in Han Chinese. | Yu JT et al. | — | 2010 | → |
| SNPs and coronary angiography: can vascular biology be done from angiograms? | Crossman DC | — | 2010 | → |
| Stem cell models of cardiac development and disease. | Musunuru K et al. | — | 2010 | → |
| Systems genetics analysis of gene-by-environment interactions in human cells. | Romanoski CE et al. | — | 2010 | → |
| Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. | Visel A et al. | — | 2010 | → |
| The 9p21.3 locus: platelets enter the fray. | Bray PF et al. | — | 2010 | → |
| The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease. | Patel RS et al. | — | 2010 | → |
| The epidemiology of diabetes in Korea: from the economics to genetics. | Cho NH | — | 2010 | → |
| The genetics of cardiovascular disease: new insights from emerging approaches. | Chico TJ et al. | — | 2010 | → |
| The genetics of ischaemic stroke. | Matarin M et al. | — | 2010 | → |
| The genetics of obesity and the metabolic syndrome. | Monda KL et al. | — | 2010 | → |
| The genome-wide association study--a new era for common polygenic disorders. | Roberts R et al. | — | 2010 | → |
| The interleukin-1 cluster, dyslipidaemia and risk of myocardial infarction. | Keavney B | — | 2010 | → |
| The KIF6 collapse. | Topol EJ et al. | — | 2010 | → |
| The past, present, and future of direct-to-consumer genetic tests. | Helgason A et al. | — | 2010 | → |
| The pursuit of genome-wide association studies: where are we now? | Ku CS et al. | — | 2010 | → |
| The relationship between smoking and replicated sequence variants on chromosomes 8 and 9 with familial intracranial aneurysm. | Deka R et al. | — | 2010 | → |
| The transcription factor GATA-2 does not associate with angiographic coronary artery disease in the Ottawa Heart Genomics and Cleveland Clinic GeneBank Studies. | Dandona S et al. | — | 2010 | → |
| Translating genomic analyses into improved management of coronary artery disease. | Johansen CT et al. | — | 2010 | → |
| Untargeted metabolic profiling reveals potential biomarkers in myocardial infarction and its application. | Yao H et al. | — | 2010 | → |
| Variation in recovery: Role of gender on outcomes of young AMI patients (VIRGO) study design. | Lichtman JH et al. | — | 2010 | → |
| Variations of six transmembrane epithelial antigen of prostate 4 (STEAP4) gene are associated with metabolic syndrome in a female Uygur general population. | Nanfang L et al. | — | 2010 | → |
| 9p21 is a shared susceptibility locus strongly for coronary artery disease and weakly for ischemic stroke in Chinese Han population. | Ding H et al. | — | 2009 | → |
| A combination of proatherogenic single-nucleotide polymorphisms is associated with increased risk of coronary artery disease and myocardial infarction in Asian Indians. | Poduri A et al. | — | 2009 | → |
| A common copy number variation on chromosome 6 association with the gene expression level of endothelin 1 in transformed B lymphocytes from three racial groups. | Sun YV et al. | — | 2009 | → |
| A common variant at 9p21 is associated with sudden and arrhythmic cardiac death. | Newton-Cheh C et al. | — | 2009 | → |
| A common variant in chromosome 9p21 associated with coronary artery disease in Asian Indians. | Maitra A et al. | — | 2009 | → |
| Advances in systems biology are enhancing our understanding of disease and moving us closer to novel disease treatments. | Schadt EE et al. | — | 2009 | → |
| A Fast Implementation of a Scan Statistic for Identifying Chromosomal Patterns of Genome Wide Association Studies. | Sun YV et al. | — | 2009 | → |
| A genetic variant on chromosome 9p21 and incident heart failure in the ARIC study. | Yamagishi K et al. | — | 2009 | → |
| A genome-wide association study primer for clinicians. | Wang TH et al. | — | 2009 | → |
| Aging increases p16 INK4a expression in vascular smooth-muscle cells. | Rodriguez-Menocal L et al. | — | 2009 | → |
| Analysis of complex disease association and linkage studies using the University of California Santa Cruz Genome Browser. | Wang T et al. | — | 2009 | → |
| A quantitative model for age-dependent expression of the p16INK4a tumor suppressor. | Tsygankov D et al. | — | 2009 | → |
| Association and functional analyses of MEF2A as a susceptibility gene for premature myocardial infarction and coronary artery disease. | Guella I et al. | — | 2009 | → |
| Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: Design of prospective meta-analyses of genome-wide association studies from 5 cohorts. | Psaty BM et al. | — | 2009 | → |
| Common genetic variants on chromosome 9p21 confers risk of ischemic stroke: a large-scale genetic association study. | Smith JG et al. | — | 2009 | → |
| Common polymorphisms influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease. | Stark K et al. | — | 2009 | → |
| Creating a genetic risk score for coronary artery disease. | Dandona S et al. | — | 2009 | → |
| Detecting SNP-expression associations: a comparison of mutual information and median test with standard statistical approaches. | Szymczak S et al. | — | 2009 | → |
| Direct-to-consumer genetic tests: beyond medical regulation? | Magnus D et al. | — | 2009 | → |
| Enrichment of sequencing targets from the human genome by solution hybridization. | Tewhey R et al. | — | 2009 | → |
| Evidence for association between polycystic ovary syndrome (PCOS) and TCF7L2 and glucose intolerance in women with PCOS and TCF7L2. | Biyasheva A et al. | — | 2009 | → |
| Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging. | Liu Y et al. | — | 2009 | → |
| Fostering translation of genetics research: an NIDDK perspective. | Akolkar B et al. | — | 2009 | → |
| From epidemiology to lysyl oxidase like one (LOXL1) polymorphisms discovery: phenotyping and genotyping exfoliation syndrome and exfoliation glaucoma in Iceland. | Jonasson F | — | 2009 | → |
| Gene-gene and gene-environment interactions: new insights into the prevention, detection and management of coronary artery disease. | Lanktree MB et al. | — | 2009 | → |
| Genetic architecture of quantitative traits in mice, flies, and humans. | Flint J et al. | — | 2009 | → |
| Genetic basis of beta-cell dysfunction in man. | Groop L et al. | — | 2009 | → |
| Genetic prognostic and predictive markers in colorectal cancer. | Walther A et al. | — | 2009 | → |
| Genetics and the general physician: insights, applications and future challenges. | Knight JC | — | 2009 | → |
| Genetics of coronary artery disease: focus on genome-wide association studies. | Baudhuin LM | — | 2009 | → |
| Genetic variants associated with Lp(a) lipoprotein level and coronary disease. | Clarke R et al. | — | 2009 | → |
| Genetic variants on chromosome 9p21 and ischemic stroke in Chinese. | Hu WL et al. | — | 2009 | → |
| Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. | Myocardial Infarction Genetics Consortium et al. | — | 2009 | → |
| Genome-wide association studies for atherosclerotic vascular disease and its risk factors. | Ding K et al. | — | 2009 | → |
| Genome-wide association studies in type 1 diabetes, inflammatory bowel disease and other immune-mediated disorders. | Hakonarson H et al. | — | 2009 | → |
| Genome-wide association studies of coronary artery disease and heart failure: where are we going? | Dorn GW et al. | — | 2009 | → |
| Genomics and cardiovascular drug development. | Plump AS et al. | — | 2009 | → |
| Genomics of cardiovascular disease. | Manace LC et al. | — | 2009 | → |
| Genomic view of factors leading to plaque instability. | Dandona S et al. | — | 2009 | → |
| Genomic views of distant-acting enhancers. | Visel A et al. | — | 2009 | → |
| GWAS or Gee Whiz, PSAS or Pshaw: elucidating the biologic and clinical significance of genetic variation in cardiovascular disease. | Landstrom AP et al. | — | 2009 | → |
| Haplotypes encompassing the KIAA0391 and PSMA6 gene cluster confer a genetic link for myocardial infarction and coronary artery disease. | Alsmadi O et al. | — | 2009 | → |
| Human genetic variation and its contribution to complex traits. | Frazer KA et al. | — | 2009 | → |
| Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis. | Schaefer AS et al. | — | 2009 | → |
| Identification of genetic markers associated with high-density lipoprotein-cholesterol by genome-wide screening in a Japanese population: the Suita study. | Hiura Y et al. | — | 2009 | → |
| INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis. | Liu Y et al. | — | 2009 | → |
| Irrelevance of the chromosome 9p21.3 locus for acute cardiovascular events and restenosis. | Horne BD et al. | — | 2009 | → |
| Joint analysis of tightly linked SNPs in screening step of genome-wide association studies leads to increased power. | Becker T et al. | — | 2009 | → |
| Lack of association between a common polymorphism near the INSIG2 gene and BMI, myocardial infarction, and cardiovascular risk factors. | Wiedmann S et al. | — | 2009 | → |
| Lack of association of chromosome 9p21.3 genotype with cardiovascular function in persons with stable coronary artery disease: The heart and soul study. | Dandona S et al. | — | 2009 | → |
| Lp(a) lipoprotein redux--from curious molecule to causal risk factor. | Kathiresan S | — | 2009 | → |
| Megakaryoblastic leukemia factor-1 gene in the susceptibility to coronary artery disease. | Hinohara K et al. | — | 2009 | → |
| Memory management in genome-wide association studies. | Chen X et al. | — | 2009 | → |
| Methods for analysis in pharmacogenomics: lessons from the Pharmacogenetics Research Network Analysis Group. | Srinivasan BS et al. | — | 2009 | → |
| Molecular genetics of atherosclerosis. | Roy H et al. | — | 2009 | → |
| MTAP and CDKN2B genes are associated with myocardial infarction in Chinese Hans. | Yang XC et al. | — | 2009 | → |
| MTAP gene is associated with ischemic stroke in Chinese Hans. | Li SJ et al. | — | 2009 | → |
| Multi-ethnic genetic association study of carotid intima-media thickness using a targeted cardiovascular SNP microarray. | Lanktree MB et al. | — | 2009 | → |
| Multi-tissue coexpression networks reveal unexpected subnetworks associated with disease. | Dobrin R et al. | — | 2009 | → |
| New common variants affecting susceptibility to basal cell carcinoma. | Stacey SN et al. | — | 2009 | → |
| New susceptibility locus for coronary artery disease on chromosome 3q22.3. | Erdmann J et al. | — | 2009 | → |
| No association of chromosome 9p21.3 variation with clinical and angiographic outcomes after placement of drug-eluting stents. | Hoppmann P et al. | — | 2009 | → |
| Obstructive sleep apnea and cardiovascular disease: a perspective and future directions. | Pack AI et al. | — | 2009 | → |
| Peroxisome proliferator-activated receptor gamma polymorphisms and coronary heart disease. | Dallongeville J et al. | — | 2009 | → |
| Personalized medicine in coronary artery disease: insights from genomic research. | Lee SH et al. | — | 2009 | → |
| Pharmacogenetics and functional genomics in asthma. | Sleiman PM et al. | — | 2009 | → |
| Polymorphisms of the immune response genes: selected biological, methodical and medical aspects. | Kubistova Z et al. | — | 2009 | → |
| Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants. | Folkersen L et al. | — | 2009 | → |
| Replication studies for the association of PSMA6 polymorphism with coronary artery disease in East Asian populations. | Hinohara K et al. | — | 2009 | → |
| Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. | Gschwendtner A et al. | — | 2009 | → |
| Stable patterns of gene expression regulating carbohydrate metabolism determined by geographic ancestry. | Schisler JC et al. | — | 2009 | → |
| Strengthening the reporting of genetic association studies (STREGA): an extension of the strengthening the reporting of observational studies in epidemiology (STROBE) statement. | Little J et al. | — | 2009 | → |
| Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE statement. | Little J et al. | — | 2009 | → |
| Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE Statement. | Little J et al. | — | 2009 | → |
| STrengthening the REporting of Genetic Association studies (STREGA)--an extension of the STROBE statement. | Little J et al. | — | 2009 | → |
| STrengthening the REporting of Genetic Association Studies (STREGA)--an extension of the STROBE statement. | Little J et al. | — | 2009 | → |
| The 9p21 myocardial infarction risk allele increases risk of peripheral artery disease in older people. | Cluett C et al. | — | 2009 | → |
| The discovery of genes implicated in myocardial infarction. | Ouwehand WH et al. | — | 2009 | → |
| The functional variant rs1048990 in PSMA6 is associated with susceptibility to myocardial infarction in a Chinese population. | Liu X et al. | — | 2009 | → |
| The genetic signatures of noncoding RNAs. | Mattick JS | — | 2009 | → |
| The impact of divergence time on the nature of population structure: an example from Iceland. | Price AL et al. | — | 2009 | → |
| The impact of newly identified loci on coronary heart disease, stroke and total mortality in the MORGAM prospective cohorts. | Karvanen J et al. | — | 2009 | → |
| The myocardial infarction associated CDKN2A/CDKN2B locus on chromosome 9p21 is associated with stroke independently of coronary events in patients with hypertension. | Wahlstrand B et al. | — | 2009 | → |
| The null distributions of test statistics in genomewide association studies. | Chen X et al. | — | 2009 | → |
| The Pakistan Risk of Myocardial Infarction Study: a resource for the study of genetic, lifestyle and other determinants of myocardial infarction in South Asia. | Saleheen D et al. | — | 2009 | → |
| The paraoxonase gene family and atherosclerosis. | Seo D et al. | — | 2009 | → |
| The role of genomics in the neonatal ICU. | Maresso K et al. | — | 2009 | → |
| The search for genetic polymorphisms in the homocysteine/folate pathway that contribute to the etiology of human neural tube defects. | Molloy AM et al. | — | 2009 | → |
| The year in epidemiology, health services research, and outcomes research. | Hlatky MA et al. | — | 2009 | → |
| Three SNPs on chromosome 9p21 confer increased risk of myocardial infarction in Chinese subjects. | Zhang Q et al. | — | 2009 | → |
| Understanding cardiovascular disease through the lens of genome-wide association studies. | Arking DE et al. | — | 2009 | → |
| Validation of eight genetic risk factors in East Asian populations replicated the association of BRAP with coronary artery disease. | Hinohara K et al. | — | 2009 | → |
| Variant on 9p21 strongly associates with coronary heart disease, but lacks association with common stroke. | Lemmens R et al. | — | 2009 | → |
| Willows: a memory efficient tree and forest construction package. | Zhang H et al. | — | 2009 | → |
| Worldwide patterns of haplotype diversity at 9p21.3, a locus associated with type 2 diabetes and coronary heart disease. | Silander K et al. | — | 2009 | → |