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From SNPedia

increased risk for coronary artery disease
Geno Mag Summary
(C;C) 4 1.9x increased risk for coronary artery disease
(C;G) 3 1.5x increased risk for CAD
(G;G) 0 normal
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
dbSNP (classic)rs1333049
1000 genomesrs1333049
GWAS Ctlgrs1333049
Max Magnitude4
? (C;C) (C;G) (G;G) 28

CPMC Logo.png

This SNP has been recognized by the Coriell Personalized Medicine Collaborative ICOB.
Additional information is available here

SNP rs1333049
PubMedID [PMID 17554300OA-icon.png]
Condition Coronary heart disease
Risk Allele C
pValue 1.00E-013
OR 1.47
95% CI 1.27-1.70
GWAS snp
PMID [PMID 24262325OA-icon.png]
Trait Coronary artery disease
Title Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.
Risk Allele C
P-val 3E-56
Odds Ratio 1.24 [1.21-1.28]
GWAS snp
PMID [PMID 22144573OA-icon.png]
Trait Coronary artery calcification
Title Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction.
Risk Allele C
P-val 3E-24
Odds Ratio 0.199 [0.16-0.24] % increase
GWAS snp
PMID [PMID 21626137OA-icon.png]
Trait Coronary heart disease
Title Two-marker association tests yield new disease associations for coronary artery disease and hypertension.
Risk Allele
P-val 7E-14
Odds Ratio
GWAS snp
PMID [PMID 21606135OA-icon.png]
Trait Coronary heart disease
Title A Genome-wide Association Study Identifies LIPA as a Susceptibility Gene for Coronary Artery Disease.
Risk Allele C
P-val 7E-58
Odds Ratio 1.2700 [1.23-1.31]
GWAS snp
PMID [PMID 17634449OA-icon.png]
Trait Coronary heart disease
Title Genomewide association analysis of coronary artery disease.
Risk Allele C
P-val 3E-19
Odds Ratio 1.36 [1.27-1.46]
GWAS snp
PMID [PMID 17554300OA-icon.png]
Trait Coronary heart disease
Title Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
Risk Allele C
P-val 1E-13
Odds Ratio 1.47 [1.27-1.70]

rs1333049 has been reported in a large study to be associated with heart disease, in particular, coronary artery disease.

The risk allele (oriented to the dbSNP entry) is most likely (C); the odds ratio associated with heterozygotes is 1.47 (CI 1.27-1.70), and for homozygotes, 1.9 (CI 1.61-2.24). [PMID 17554300OA-icon.png]

This SNP has also been reported to have the highest association of any SNP studied in a subsequent experiment conducted with the resources of the German MI [Myocardial Infarction] Family Study. [PMID 17634449, PMID 18362232]

The initial studies were conducted on Caucasian populations. A subsequent study of Japanese and Korean patients has also found rs1333049 to be associated with increased coronary artery disease risk, with roughly similar odds ratios.[PMID 18264662]

Further reading (with comments)

[PMID 18652946] Association of genetic variation on chromosome 9p21 with susceptibility and progression of atherosclerosis: a population-based, prospective study.

- A long-term study of a cohort of 769 individuals finds that the rs1333049(C) allele was associated with:

  • prevalent carotid atherosclerosis (odds ratio 1.46, 1.43 or 1.44, from data collected in 1990, 1995, and 2000, respectively, all with CI: ~1.1-1.9);
  • progression of atherosclerosis (for example, odds ratio 1.87 (CI: 1.44 to 2.42) during 1995 to 2000);
  • incident cardiovascular disease (hazard ratio: 1.37 (CI: 1.05 to 1.79)}.
  • Note: this SNP and rs10757278 are practically equivalent, with linkage r2=1 in HapMap CEU populations

[PMID 20231156OA-icon.png] A variant at chromosome 9p21 is associated with recurrent myocardial infarction and cardiac death after acute coronary syndrome: the GRACE Genetics Study.

- A study of 3,000+ patients with acute coronary sydrome (ACS) revealed that those carrying a rs1333049(C) allele were at higher risk for subsequent myocardial infarctions [adjusted hazard ratio 1.48, CI: 1.00-2.19, p = 0.048 and with recurrent MI or cardiac death (adjusted HR 1.58, CI: 1.00-2.48, p = 0.045) within 6 months after an index ACS.

[PMID 20031606OA-icon.png] The 9p21 myocardial infarction risk allele increases risk of peripheral artery disease in older people.

- A study of 2630 white individuals (mean age, 76.4 years) concluded that the rs1333049(C) allele was associated with increased prevalence of peripheral artery disease. The per allele odds ratio was 1.29 (CI: 1.06 to 1.56, p = 0.012).

[PMID 19171343OA-icon.png] Lack of association of chromosome 9p21.3 genotype with cardiovascular structure and function in persons with stable coronary artery disease: The Heart and Soul Study.

- In a cross-sectional study of individuals with stable coronary artery disease, there was no association with cardiovascular structure and function.

[PMID 18979498OA-icon.png] The impact of newly identified loci on coronary heart disease, stroke and total mortality in the MORGAM prospective cohorts.

- rs1333049 1.15x risk associated with both coronary heart disease and stroke

Further reading (no comments added)

[PMID 25232560OA-icon.png] Reduced risk of recurrent myocardial infarction in homozygous carriers of the chromosome 9p21 rs1333049 C risk allele in the contemporary percutaneous coronary intervention era: a prospective observational study

[PMID 25105296OA-icon.png] Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction

[PMID 25032714] 9p21.3 risk locus is associated with first-ever myocardial infarction in an Austrian cohort

[PMID 24573017] Associations between the CDKN2A/B, ADTRP and PDGFD Polymorphisms and the Development of Coronary Atherosclerosis in Japanese Patients

[PMID 24365123] Association of polymorphisms on chromosome 9p21.3 region with increased susceptibility of abdominal aortic aneurysm in a Chinese Han population

[PMID 24246088] Variant at 9p21 rs1333049 is associated with age of onset of coronary artery disease in a Western Indian population: a case control association study

[PMID 24163049OA-icon.png] The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts

[PMID 24087953] [Genetic predictors of myocardial infarction in subjects of young age]

[PMID 24069144OA-icon.png] Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction

[PMID 23202125OA-icon.png] Large-scale association analysis identifies new risk loci for coronary artery disease.

[PMID 23933542] The 9p21 locus does not affect risk of coronary artery disease through induction of type 1 interferons

[PMID 23787071OA-icon.png] Association of arterial stiffness with single nucleotide polymorphism rs1333049 and metabolic risk factors

[PMID 23729007OA-icon.png] Two chromosome 9p21 haplotype blocks distinguish between coronary artery disease and myocardial infarction risk.

[PMID 23587283OA-icon.png] Lack of associations of ten candidate coronary heart disease risk genetic variants and subclinical atherosclerosis in four U.S. populations: The Population Architecture using Genomics and Epidemiology (PAGE) study

[PMID 23535969] Chromosome 9p21 rs10757278 polymorphism is associated with the risk of metabolic syndrome

[PMID 23266621] Association of ANRIL polymorphism (rs1333049:C>G) with myocardial infarction and its pharmacogenomic role in hypercholesterolemia

[PMID 23202125OA-icon.png] Large-scale association analysis identifies new risk loci for coronary artery disease.

[PMID 23142796] An Italian association study and meta-analysis with previous GWAS confirm WNT4, CDKN2BAS and FN1 as the first identified susceptibility loci for endometriosis

[PMID 23086272] Association between 9p21.3 genomic markers and coronary artery disease in East Asians: a meta-analysis involving 9,813 cases and 10,710 controls

[PMID 22856164] [Evaluation of association between 9 genetic polymorphism and myocardial infarction in the Siberian population]

[PMID 22623978OA-icon.png] A Replication Study of GWAS-Derived Lipid Genes in Asian Indians: The Chromosomal Region 11q23.3 Harbors Loci Contributing to Triglycerides

[PMID 22505696] Polymorphisms of the genes encoding CD40 and growth differentiation factor 15 and in the 9p21.3 region in patients with rheumatoid arthritis and cardiovascular disease.

[PMID 22436605] Single polymorphism nucleotide rs1333049 on chromosome 9p21 is associated with carotid plaques but not with common carotid intima-media thickness in older adults. A combined analysis of the Three-City and the EVA studies.

[PMID 22396608OA-icon.png] No evidence for association of Chr 9p21 variant rs1333049 with gout in New Zealand case-control sample sets.

[PMID 22144573OA-icon.png] Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction

[PMID 21804106OA-icon.png] Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration.

[PMID 21511257] The chromosome 9p21 region and myocardial infarction in a European population

[PMID 21385355OA-icon.png] Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry

[PMID 21362310] Polymorphism on chromosome 9p21. 3 contributes to early-onset and severity of coronary artery disease in non-diabetic and type 2 diabetic patients

[PMID 21152093OA-icon.png] Sex Differential Genetic Effect of Chromosome 9p21 on Subclinical Atherosclerosis

[PMID 20691078OA-icon.png] Chromosome 9p21.3 polymorphism in a Chinese Han population is associated with angiographic coronary plaque progression in non-diabetic but not in type 2 diabetic patients

[PMID 20649639] Forearm vasodilator reactivity in homozygous carriers of the 9p21.3 rs1333049 G>C polymorphism

[PMID 20427016] Single nucleotide polymorphism rs1333049 on chromosome 9p21.3 is associated with Alzheimer's disease in Han Chinese

[PMID 20230275] Preliminary evidence of a genetic association between chromosome 9p21.3 and human longevity

[PMID 20400779] A common variant at chromosome 9P21.3 is associated with age of onset of coronary disease but not subsequent mortality.

[PMID 21558165] Genetic association of polymorphism rs1333049 with gout.

[PMID 20923989OA-icon.png] Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study: A Genome-wide association meta-analysis involving more than 22 000 cases and 60 000 controls.

[PMID 20670758] Gene dosage of the common variant 9p21 predicts severity of coronary artery disease.

[PMID 20502693OA-icon.png] Genetics and beyond--the transcriptome of human monocytes and disease susceptibility.

[PMID 20395598] 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.

[PMID 20386740OA-icon.png] Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression.

[PMID 20335276OA-icon.png] PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations.

[PMID 20098575OA-icon.png] Genetics and cardiovascular disease: Design and development of a DNA biobank.

[PMID 20031580] Common genetic variants on chromosome 9p21 confers risk of ischemic stroke: a large-scale genetic association study

[PMID 20031540] Association between the coronary artery disease risk locus on chromosome 9p21.3 and abdominal aortic aneurysm.

[PMID 20017983OA-icon.png] Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study Offspring Cohort.

[PMID 19955471OA-icon.png] 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

[PMID 19926059] No association of chromosome 9p21.3 variation with clinical and angiographic outcomes after placement of drug-eluting stents

[PMID 19709660] Single nucleotide polymorphism on chromosome 9p21 and endothelial progenitor cells in a general population cohort

[PMID 19548844] Chromosome 9p21 polymorphism is associated with myocardial infarction but not with clinical outcome in Han Chinese

[PMID 19329499OA-icon.png] A genetic variant on chromosome 9p21 and incident heart failure in the ARIC study.

[PMID 19214202OA-icon.png] Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis.

[PMID 19956784OA-icon.png] Association of variation in the chromosome 9p21 locus with myocardial infarction versus chronic coronary artery disease.

[PMID 19956433OA-icon.png] Genetics of coronary artery disease: focus on genome-wide association studies.

[PMID 19924713OA-icon.png] Use of longitudinal data in genetic studies in the genome-wide association studies era: summary of Group 14.

[PMID 19888323OA-icon.png] Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.

[PMID 19885677OA-icon.png] The transcription factor GATA-2 does not associate with angiographic coronary artery disease in the Ottawa Heart Genomics and Cleveland Clinic GeneBank Studies.

[PMID 19750184OA-icon.png] Genome-wide association studies for atherosclerotic vascular disease and its risk factors.

[PMID 19664850] Chromosome 9p21.3 genotype is associated with vascular dementia and Alzheimer's disease.

[PMID 19578366OA-icon.png] Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility.

[PMID 19475673OA-icon.png] Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke.

[PMID 19474294OA-icon.png] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.

[PMID 19463184OA-icon.png] Worldwide patterns of haplotype diversity at 9p21.3, a locus associated with type 2 diabetes and coronary heart disease.

[PMID 19343170OA-icon.png] INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.

[PMID 19173706OA-icon.png] The 9p21 susceptibility locus for coronary artery disease and the severity of coronary atherosclerosis.

[PMID 19164808OA-icon.png] Large scale association analysis of novel genetic loci for coronary artery disease

[PMID 19135198] Evaluation of the association of genetic variants on the chromosomal loci 9p21.3, 6q25.1, and 2q36.3 with angiographically characterized coronary artery disease.

[PMID 18987759OA-icon.png] Genetic testing for atherosclerosis risk: inevitability or pipe dream?

[PMID 18957718OA-icon.png] Chromosome 9p21.3 is associated with early-onset coronary heart disease in the Irish population.

[PMID 18925945OA-icon.png] Lack of association of two common polymorphisms on 9p21 with risk of coronary heart disease and myocardial infarction; results from a prospective cohort study.

[PMID 18852197OA-icon.png] Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants.

[PMID 18780302OA-icon.png] Association studies of 22 candidate SNPs with late-onset Alzheimer's disease.

[PMID 18704761OA-icon.png] Molecular genetics of myocardial infarction.

[PMID 18675980OA-icon.png] Novel genetic variants linked to coronary artery disease by genome-wide association are not associated with carotid artery intima-media thickness or intermediate risk phenotypes

[PMID 18654002] Validation of the association of genetic variants on chromosome 9p21 and 1q41 with myocardial infarction in a Japanese population.

[PMID 18599798] Coronary artery disease-associated locus on chromosome 9p21 and early markers of atherosclerosis.

[PMID 18533027OA-icon.png] Worldwide population differentiation at disease-associated SNPs.

[PMID 18224312OA-icon.png] Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.

[PMID 24732910OA-icon.png] The 9p21 locus is associated with coronary artery disease and cardiovascular events in the presence (but not in the absence) of coronary calcification

[PMID 26071660] Shared and discrepant susceptibility for carotid artery and aortic arch calcification: A genetic association study

[PMID 26944720] Polymorphisms in the long non-coding RNA CDKN2B-AS1 may contribute to higher systolic blood pressure levels in hypertensive patients.

[PMID 26950853OA-icon.png] Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium.

[PMID 27511497] Association analysis of five SNP variants with gout in the Minnan population in China.

[PMID 28639227] Association Study Between Coronary Artery Disease and rs1333049 Polymorphism at 9p21.3 Locus in Italian Population.

[PMID 28962556OA-icon.png] Association of the single nucleotide polymorphism in chromosome 9p21 and chromosome 9q33 with coronary artery disease in Chinese population.

[PMID 29905076] Genetic Variation in 9p21 and the Plasma Proteome.

[PMID 31472045] Common SNP-based haplotype analysis of the 9p21.3 gene locus as predictor coronary artery disease in Tanzanian population.

[PMID 31543200OA-icon.png] Genetic variants of chromosome 9p21.3 region associated with coronary artery disease and premature coronary artery disease in an Asian Indian population.

[PMID 31770616] ANRIL polymorphisms (rs1333049 and rs3217992) in relation to plasma CRP levels among in-patients with CHD.

[PMID 31804579OA-icon.png] The Mediterranean diet reduces the genetic risk of chromosome 9p21 for myocardial infarction in an Asian population community cohort.

[PMID 32191788OA-icon.png] ANRIL rs1333049 C/G polymorphism and coronary artery disease in a North Indian population - Gender and age specific associations.

[PMID 32392191] [Genetic Predisposition to Early Myocardial Infarction].

[PMID 32858814OA-icon.png] Association of the PSRC1 rs599839 Variant with Coronary Artery Disease in a Mexican Population.

[PMID 33054494OA-icon.png] New findings in the roles of Cyclin-dependent Kinase inhibitors 2B Antisense RNA 1 (CDKN2B-AS1) rs1333049 G/C and rs4977574 A/G variants on the risk to coronary heart disease.

[PMID 32293292OA-icon.png] Susceptible gene polymorphism in patients with three-vessel coronary artery disease.