{{Rsnum
|rsid=1333049
|Chromosome=9
|position=22125504
|Orientation=plus
|GMAF=0.4334
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|Summary=increased risk for coronary artery disease
|geno1=(C;C)
|geno2=(C;G)
|geno3=(G;G)
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;G)
| geno3=(G;G)
| CEU | 20.4 | 50.4 | 29.2
| HCB | 21.9 | 53.3 | 24.8
| JPT | 29.2 | 46.9 | 23.9
| YRI | 2.7 | 28.6 | 68.7
| ASW | 3.5 | 47.4 | 49.1
| CHB | 21.9 | 53.3 | 24.8
| CHD | 25.7 | 44.0 | 30.3
| GIH | 19.8 | 52.5 | 27.7
| LWK | 5.5 | 41.8 | 52.7
| MEX | 20.7 | 58.6 | 20.7
| MKK | 3.8 | 37.8 | 58.3
| TSI | 22.5 | 58.8 | 18.6
| HapMapRevision=28
}}{{CPMC SNP
|link=http://cpmc.coriell.org/Sections/Genes/CAD.aspx?PgId=104
}}

{{GWAS Summary
|SNP=rs1333049
|PubMedID=17554300
|Condition=Coronary heart disease
|Gene=CDKN2A,CDKN2B
|Risk Allele=C
|pValue=1.00E-013
|OR=1.47
|95CI=1.27-1.70
|OA=1
}}
{{PMID Auto GWAS
  |PMID=24262325
  |Trait=Coronary artery disease
  |Title=Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.
  |RiskAllele=C
  |Pval=3E-56
  |OR=1.24
  |ORtxt=[1.21-1.28]
  }}
{{PMID Auto GWAS
|PMID=22144573
|Trait=Coronary artery calcification
|Title=Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. 
|RiskAllele=C
|Pval=3E-24
|OR=0.199
|ORtxt=[0.16-0.24] % increase
|OA=1
}}
{{PMID Auto GWAS
|PMID=21626137
|Trait=Coronary heart disease
|Title=Two-marker association tests yield new disease associations for coronary artery disease and hypertension.
|RiskAllele=
|Pval=7E-14
|OR=
|ORtxt=
|OA=1
}}
{{PMID Auto GWAS
|PMID=21606135
|Trait=Coronary heart disease
|Title=A Genome-wide Association Study Identifies LIPA as a Susceptibility Gene for Coronary Artery Disease.
|RiskAllele=C
|Pval=7E-58
|OR=1.2700
|ORtxt=[1.23-1.31]
|OA=1
}}
{{PMID Auto GWAS
|PMID=17634449
|Trait=Coronary heart disease
|Title=Genomewide association analysis of coronary artery disease. 
|RiskAllele=C
|Pval=3E-19
|OR=1.36
|ORtxt=[1.27-1.46]
|OA=1
}}
{{PMID Auto GWAS
|PMID=17554300 
|Trait=Coronary heart disease
|Title=Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. 
|RiskAllele=C
|Pval=1E-13
|OR=1.47
|ORtxt=[1.27-1.70]
|OA=1
}}
{{omim
|desc=CORONARY HEART DISEASE, SUSCEPTIBILITY TO, 8; CHDS8
|id=611139
|rsnum=1333049
}}
{{GET Evidence
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs1333049
|overall_frequency_n=42
|overall_frequency_d=126
|overall_frequency=0.333333
|n_genomes=29
|n_genomes_annotated=0
|n_haplomes=34
|n_articles=0
|n_articles_annotated=0
|in_gwas=Y
|in_pharmgkb=Y
|autoscore=2
|webscore=N
}}

[[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|17554300|OA=1
}}

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 Auto
|PMID=18652946
|Title=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 r<sup>2</sup>=1 in HapMap CEU populations

{{PMID Auto
|PMID=20231156
|Title=A variant at chromosome 9p21 is associated with recurrent myocardial infarction and cardiac death after acute coronary syndrome: the GRACE Genetics Study.
|OA=1
}} 

- 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 Auto
|PMID=20031606
|Title=The 9p21 myocardial infarction risk allele increases risk of peripheral artery disease in older people.
|OA=1
}}
 
- 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 Auto
|PMID=19171343
|Title=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.
|OA=1
}} 

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

{{PMID Auto
|PMID=18979498
|Title=The impact of newly identified loci on coronary heart disease, stroke and total mortality in the MORGAM prospective cohorts.
|OA=1
}} 

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

{{ neighbor
| rsid = 10757278
| distance = 1026
}}
{{ neighbor
| rsid = 10811661
| distance = 8591
}}
{{ neighbor
| rsid = 1333048
| distance = 156
}}

'''Further reading (no comments added)'''

{{PMID Auto
|PMID=25032714
|Title=9p21.3 risk locus is associated with first-ever myocardial infarction in an Austrian cohort
}}
{{PMID Auto
|PMID=24573017
|Title=Associations between the CDKN2A/B, ADTRP and PDGFD Polymorphisms and the Development of Coronary Atherosclerosis in Japanese Patients
}}
{{PMID Auto
|PMID=24246088
|Title=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 Auto
|PMID=24163049
|Title=The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts
}}
{{PMID Auto
|PMID=24087953
|Title=[Genetic predictors of myocardial infarction in subjects of young age]
}}
{{PMID Auto
|PMID=24069144
|Title=Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction
|OA=1
}}
{{PMID Auto
|PMID=23202125
|Title=Large-scale association analysis identifies new risk loci for coronary artery disease.
}}
{{PMID Auto
|PMID=23933542
|Title=The 9p21 locus does not affect risk of coronary artery disease through induction of type 1 interferons
}}
{{PMID Auto
|PMID=23787071
|Title=Association of arterial stiffness with single nucleotide polymorphism rs1333049 and metabolic risk factors
|OA=1
}}
{{PMID Auto
|PMID=23729007
|Title=Two chromosome 9p21 haplotype blocks distinguish between coronary artery disease and myocardial infarction risk.
}}
{{PMID Auto
|PMID=23587283
|Title=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 Auto
|PMID=23535969
|Title=Chromosome 9p21 rs10757278 polymorphism is associated with the risk of metabolic syndrome
}}
{{PMID Auto
|PMID=23266621
|Title=Association of ANRIL polymorphism (rs1333049:C&gt;G) with myocardial infarction and its pharmacogenomic role in hypercholesterolemia
}}
{{PMID Auto
|PMID=23142796
|Title=An Italian association study and meta-analysis with previous GWAS confirm WNT4, CDKN2BAS and FN1 as the first identified susceptibility loci for endometriosis
}}
{{PMID Auto
|PMID=23086272
|Title=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 Auto
|PMID=22856164
|Title=[Evaluation of association between 9 genetic polymorphism and myocardial infarction in the Siberian population]
}}
{{PMID Auto
|PMID=22623978
|Title=A Replication Study of GWAS-Derived Lipid Genes in Asian Indians: The Chromosomal Region 11q23.3 Harbors Loci Contributing to Triglycerides
|OA=1
}}
{{PMID Auto
|PMID=22505696
|Title=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 Auto
|PMID=22436605
|Title=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 Auto
|PMID=22396608
|Title=No evidence for association of Chr 9p21 variant rs1333049 with gout in New Zealand case-control sample sets.
|OA=1
}}
{{PMID Auto
|PMID=22144573
|Title=Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction
|OA=1
}}
{{PMID Auto
|PMID=21804106
|Title=Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration.
|OA=1
}}
{{PMID Auto
|PMID=21511257
|Title=The chromosome 9p21 region and myocardial infarction in a European population
}}
{{PMID Auto
|PMID=21385355
|Title=Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry
|OA=1
}}
{{PMID Auto
|PMID=21362310
|Title=Polymorphism on chromosome 9p21. 3 contributes to early-onset and severity of coronary artery disease in non-diabetic and type 2 diabetic patients
}}
{{PMID Auto
|PMID=21152093
|Title=Sex Differential Genetic Effect of Chromosome 9p21 on Subclinical Atherosclerosis
|OA=1
}}
{{PMID Auto
|PMID=20691078
|Title=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
|OA=1
}}
{{PMID Auto
|PMID=20649639
|Title=Forearm vasodilator reactivity in homozygous carriers of the 9p21.3 rs1333049 G&gt;C polymorphism
}}
{{PMID Auto
|PMID=20427016
|Title=Single nucleotide polymorphism rs1333049 on chromosome 9p21.3 is associated with Alzheimer's disease in Han Chinese
}}
{{PMID Auto
|PMID=20230275
|Title=Preliminary evidence of a genetic association between chromosome 9p21.3 and human longevity
}}
{{PMID Auto
|PMID=20400779
|Title=A common variant at chromosome 9P21.3 is associated with age of onset of coronary disease but not subsequent mortality.
}}
{{PMID Auto
|PMID=21558165
|Title=Genetic association of polymorphism rs1333049 with gout.
}}
{{PMID Auto
|PMID=20923989
|Title=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.
|OA=1
}}
{{PMID Auto
|PMID=20670758
|Title=Gene dosage of the common variant 9p21 predicts severity of coronary artery disease.
}}
{{PMID Auto
|PMID=20502693
|Title=Genetics and beyond--the transcriptome of human monocytes and disease susceptibility.
|OA=1
}}
{{PMID Auto
|PMID=20395598
|Title=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 Auto
|PMID=20386740
|Title=Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression.
|OA=1
}}
{{PMID Auto
|PMID=20335276
|Title=PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations.
|OA=1
}}
{{PMID Auto
|PMID=20098575
|Title=Genetics and cardiovascular disease: Design and development of a DNA biobank.
|OA=1
}}
{{PMID Auto
|PMID=20031580
|Title=Common genetic variants on chromosome 9p21 confers risk of ischemic stroke: a large-scale genetic association study
}}
{{PMID Auto
|PMID=20031540
|Title=Association between the coronary artery disease risk locus on chromosome 9p21.3 and abdominal aortic aneurysm.
}}
{{PMID Auto
|PMID=20017983
|Title=Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study Offspring Cohort.
|OA=1
}}
{{PMID Auto
|PMID=19955471
|Title=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
|OA=1
}}
{{PMID Auto
|PMID=19926059
|Title=No association of chromosome 9p21.3 variation with clinical and angiographic outcomes after placement of drug-eluting stents
}}
{{PMID Auto
|PMID=19709660
|Title=Single nucleotide polymorphism on chromosome 9p21 and endothelial progenitor cells in a general population cohort
}}
{{PMID Auto
|PMID=19548844
|Title=Chromosome 9p21 polymorphism is associated with myocardial infarction but not with clinical outcome in Han Chinese
}}
{{PMID Auto
|PMID=19329499
|Title=A genetic variant on chromosome 9p21 and incident heart failure in the ARIC study.
|OA=1
}}
{{PMID Auto
|PMID=19214202
|Title=Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis.
|OA=1
}}

{{PMID Auto
|PMID=19956784
|Title=Association of variation in the chromosome 9p21 locus with myocardial infarction versus chronic coronary artery disease.
|OA=1
}}
{{PMID Auto
|PMID=19956433
|Title=Genetics of coronary artery disease: focus on genome-wide association studies.
|OA=1
}}
{{PMID Auto
|PMID=19924713
|Title=Use of longitudinal data in genetic studies in the genome-wide association studies era: summary of Group 14.
|OA=1
}}
{{PMID Auto
|PMID=19888323
|Title=Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.
|OA=1
}}
{{PMID Auto
|PMID=19885677
|Title=The transcription factor GATA-2 does not associate with angiographic coronary artery disease in the Ottawa Heart Genomics and Cleveland Clinic GeneBank Studies.
|OA=1
}}
{{PMID Auto
|PMID=19750184
|Title=Genome-wide association studies for atherosclerotic vascular disease and its risk factors.
|OA=1
}}
{{PMID Auto
|PMID=19664850
|Title=Chromosome 9p21.3 genotype is associated with vascular dementia and Alzheimer's disease.
}}
{{PMID Auto
|PMID=19578366
|Title=Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility.
|OA=1
}}
{{PMID Auto
|PMID=19475673
|Title=Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke.
|OA=1
}}
{{PMID Auto
|PMID=19474294
|Title=Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
|OA=1
}}
{{PMID Auto
|PMID=19463184
|Title=Worldwide patterns of haplotype diversity at 9p21.3, a locus associated with type 2 diabetes and coronary heart disease.
|OA=1
}}
{{PMID Auto
|PMID=19343170
|Title=INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.
|OA=1
}}
{{PMID Auto
|PMID=19173706
|Title=The 9p21 susceptibility locus for coronary artery disease and the severity of coronary atherosclerosis.
|OA=1
}}
{{PMID Auto
|PMID=19164808
|Title=Large scale association analysis of novel genetic loci for coronary artery disease
|OA=1
}}
{{PMID Auto
|PMID=19135198
|Title=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 Auto
|PMID=18987759
|Title=Genetic testing for atherosclerosis risk: inevitability or pipe dream?
|OA=1
}}
{{PMID Auto
|PMID=18957718
|Title=Chromosome 9p21.3 is associated with early-onset coronary heart disease in the Irish population.
|OA=1
}}
{{PMID Auto
|PMID=18925945
|Title=Lack of association of two common polymorphisms on 9p21 with risk of coronary heart disease and myocardial infarction; results from a prospective cohort study.
|OA=1
}}
{{PMID Auto
|PMID=18852197
|Title=Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants.
|OA=1
}}
{{PMID Auto
|PMID=18780302
|Title=Association studies of 22 candidate SNPs with late-onset Alzheimer's disease.
|OA=1
}}
{{PMID Auto
|PMID=18704761
|Title=Molecular genetics of myocardial infarction.
|OA=1
}}
{{PMID Auto
|PMID=18675980
|Title=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
|OA=1
}}
{{PMID Auto
|PMID=18654002
|Title=Validation of the association of genetic variants on chromosome 9p21 and 1q41 with myocardial infarction in a Japanese population.
}}
{{PMID Auto
|PMID=18599798
|Title=Coronary artery disease-associated locus on chromosome 9p21 and early markers of atherosclerosis.
}}
{{PMID Auto
|PMID=18533027
|Title=Worldwide population differentiation at disease-associated SNPs.
|OA=1
}}
{{PMID Auto
|PMID=18224312
|Title=Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.
|OA=1
}}

{{PharmGKB
|RSID=rs1333049
|Name_s=
|Gene_s=-
|Feature=
|Evidence=PubMed ID:17554300; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS Results: Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls (Initial Sample Size: 1,926 cases, 2,938 controls; Replication Sample Size: (see Samani 2007); Risk Allele: rs1333049-C). This variant is associated with coronary disease.
|Drugs=
|Drug Classes=
|Diseases=Coronary Disease
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA162356642
}}

{{PMID Auto
|PMID=25105296
|Title=Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction
}}

{{PMID Auto
|PMID=24365123
|Title=Association of polymorphisms on chromosome 9p21.3 region with increased susceptibility of abdominal aortic aneurysm in a Chinese Han population
}}

{{PMID Auto
|PMID=25232560
|Title=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
}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Affy GenomeWide 6 }}
{{on chip | Affy GenomeWide 6}}
{{on chip | Affy500k }}