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From SNPedia

Geno Mag Summary
(A;A) 1.9 0.78x reduced risk for Coronary Heart Disease. 0.77x reduced risk for Brain Aneurysm and Abdominal Aortic Aneurysm.
(A;G) 2 1.3x risk for Heart Attack. Normal risk for Abdominal Aortic Aneurysm and Brain Aneurysm.
(G;G) 2.5 1.6x risk for Heart Attack; 1.3x risk for Abdominal Aortic Aneurysm and Brain Aneurysm.
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
dbSNP (classic)rs10757278
1000 genomesrs10757278
GWAS Ctlgrs10757278
Max Magnitude2.5
? (A;A) (A;G) (G;G) 28

This SNP, rs10757278, is one of several clustered together in a region of chromosome 9 that has been linked to increased risk for heart disease and potentially diabetes. The overall estimate of heart disease cases that may involve this SNP (or related ones nearby) is said to be 20-30%.

The risk allele, rs10757278(G), shows an increased association for myocardial infarctions ("MI"; heart attacks) both in general and more specifically in so-called early onset MI. The odds ratio relative to rs10757278(A:A) "noncarrier" individuals for rs10757278(G;G) individuals is 1.64 (CI: 1.47-1.82), and for carriers of one risk allele, i.e. rs10757278(A;G) individuals, 1.26 (CI: 1.16-1.36). [PMID 17478679]

For early onset MI, the odds are slightly higher; homozygote rs10757278(G;G) individuals have an odds ratio of 2.02 (CI: 1.72-2.36), heterozygote rs10757278(A;G) individuals 1.49 (CI: 1.31-1.69) compared to noncarriers. To put it another way, men under the age of 50 and women under the age of 60 who are rs10757278(G:G) individuals have about twice the risk of having a heart attack compared to rs10757278(A:A) individuals. [PMID 17478679]

Two other SNPs in this region with similar reports are rs10757274 and rs2383206.

In an extension of the research reported above, the rs10757278(G) allele has been found to be associated with stroke as defined by abdominal aortic aneurysm (AAA; odds ratio 1.31, p=1.2x10e-12) and Intracranial Aneurysm (odds ratio 1.29, p=2.5x10e-6), but not with type-2 diabetes. The AA genotype appears to be protective, with 0.77x odds of developing abdominal aortic aneurysm as reported by DeCode. [PMID 18176561]

[PMID 18048766] This SNP was also associated with increased risk for coronary artery disease in a Korean population.

[PMID 18066490] Also found to be significant in a study of 416 Italian myocardial infarction patients.

[PMID 19319159OA-icon.png] A study and meta-analysis of 2,000+ Belgians concluded that rs10757278 is associated with increased risk for coronary artery disease but not ischemic cerebrovascular disease.

  • Note: this SNP and rs1333049 are practically equivalent, with linkage r2=1 in HapMap CEU populations
SNP rs10757278
PubMedID [PMID 17478679]
Condition Myocardial infarction
Risk Allele G
pValue 1.00E-020
OR 1.28
95% CI 1.22-1.35

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

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


[PMID 19293724] The myocardial infarction associated CDKN2A/CDKN2B locus on chromosome 9p21 is associated with stroke independently of coronary events in patients with hypertension

[PMID 19805338OA-icon.png] A quantitative model for age-dependent expression of the p16INK4a tumor suppressor

[PMID 20031606OA-icon.png] The 9p21 Myocardial Infarction Risk Allele Increases Risk of Peripheral Artery Disease in Older People

[PMID 20031605] 9p21 is a Shared Susceptibility Locus Strongly for Coronary Artery Disease and Weakly for Ischemic Stroke in Chinese Han Population

[PMID 20190001OA-icon.png] The Relationship Between Smoking and Replicated Sequence Variants on Chromosomes 8 and 9 With Familial Intracranial Aneurysm

[PMID 20305218] C-B3-03: Association of Epidemiologic and Genetic Factors With Abdominal Aortic Aneurysm (AAA)

[PMID 18048766] coronary artery disease rs1075727 and rs2383206

[PMID 18048766] myocardial infarction rs2383207 and rs10757278

The association remained significant after adjusting for significant clinical covariates (P=0.001 to 0.024). We identified one risk haplotype (GGGG; P=0.017) and one protective haplotype (AAAA; P=0.007) for development of CAD. Further analysis suggested that the SNPs probably confer susceptibility to CAD in a dominance model (covariates-adjusted P=0.001 to 0.024; OR=2.37 to 1.54).

[PMID 20729229OA-icon.png] The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease

[PMID 20871623OA-icon.png] Genetic analysis of six SNPs in candidate genes associated with high cross-race risk of development of thoracic aortic aneurysms and dissections in Chinese Han population

[PMID 21088391] Exploration of a Hypothesized Independent Association of a Common 9p21.3 Gene Variant and Ischemic Stroke in Patients with and without Angiographic Coronary Artery Disease

[PMID 21315566] Type 2 diabetes and polymorphisms on chromosome 9p21: A meta-analysis

[PMID 21444365OA-icon.png] Association of a sequence variant in DAB2IP with coronary heart disease

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

[PMID 19860767] Genetic cardiovascular risk factors and age-related macular degeneration

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

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

[PMID 18362232OA-icon.png] Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease.

[PMID 18443000OA-icon.png] Susceptibility locus for clinical and subclinical coronary artery disease at chromosome 9p21 in the multi-ethnic ADVANCE study.

[PMID 18459066] A common variant on chromosome 9p21 affects the risk of early-onset coronary artery disease.

[PMID 18469204OA-icon.png] Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians.

[PMID 18505420OA-icon.png] Four SNPS on chromosome 9p21 confer risk to premature, familial CAD and MI in an American Caucasian population (GeneQuest).

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

[PMID 18854858OA-icon.png] Sequence variant on 9p21 is associated with the presence of abdominal aortic aneurysm disease but does not have an impact on aneurysmal expansion.

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

[PMID 19002430] Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population.

[PMID 19033589OA-icon.png] Interaction between poor glycemic control and 9p21 locus on risk of coronary artery disease in type 2 diabetes.

[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.

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

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

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

[PMID 19359634OA-icon.png] Update on the genetics of stroke and cerebrovascular disease 2008.

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

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

[PMID 19503741OA-icon.png] Coding variant Met72Thr in the PEDF gene and risk of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

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

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

[PMID 19752551OA-icon.png] Polymorphisms associated with both noncardioembolic stroke and coronary heart disease: vienna stroke registry.

[PMID 19753309OA-icon.png] SOD2 gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

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

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

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

[PMID 20395606OA-icon.png] Chromosome 9p21 in ischemic stroke: population structure and meta-analysis.

[PMID 20395613] Confirmation of an association of single-nucleotide polymorphism rs1333040 on 9p21 with familial and sporadic intracranial aneurysms in Japanese patients.

[PMID 20696043OA-icon.png] Replication of the association of chromosomal region 9p21.3 with generalized aggressive periodontitis (gAgP) using an independent case-control cohort.

[PMID 20858033] Haplotypes on 9p21 modify the risk for coronary artery disease among Indians.

[PMID 20974651] Association between genetic variation on chromosome 9p21 and aneurysmal subarachnoid haemorrhage.

[PMID 21307941OA-icon.png] 9p21 DNA variants associated with coronary artery disease impair interferon-gamma signalling response.

[PMID 21896860] Association of genetic variation on chromosome 9p21 with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

[PMID 22034006] Variants on chromosome 9p21.3 correlated with ANRIL expression contribute to stroke risk and recurrence in a large prospective stroke population.

[PMID 22042884OA-icon.png] Association of genetic variants and incident coronary heart disease in multiethnic cohorts: the PAGE study.

[PMID 22198471] Genetic variants at chromosome 9p21, 10p15 and 10q22 and breast cancer susceptibility in a Chinese population.

[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 23134948OA-icon.png] Association between 9p21 genetic variants and mortality risk in a prospective cohort of patients with type 2 diabetes (ZODIAC-15)

Brain Aneurysm

[PMID 23388737] Association of Single Nucleotide Polymorphisms on Chromosome 9p21.3 With Cardiovascular Death in Kidney Transplant Recipients

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

[22198471?dopt=Abstract PMID 22198471] in Chinese women no significant breast cancer association at rs1011970, rs10757278 or rs2380205

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

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

[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 22946666OA-icon.png] The rs10757278 polymorphism of the 9p21.3 locus is associated with premature coronary artery disease in Polish patients.

[PMID 22975211] Meta-analysis of genetic association of chromosome 9p21 with early-onset coronary artery disease.

[PMID 23733552OA-icon.png] Genetic risk factors for intracranial aneurysms: a meta-analysis in more than 116,000 individuals.

[PMID 24782050] Gene polymorphisms associated with susceptibility to coronary artery disease in Han Chinese people

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

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

[PMID 25724239] Sequence Variants on Chromosome 9p21 are Associated with Ischemic Stroke and the Lipids Level in Chinese Han Population

[PMID 26109989OA-icon.png] The cardiovascular implication of single nucleotide polymorphisms of chromosome 9p21 locus among Arab population

[PMID 26615606] The 9p21 polymorphism is linked with atrial fibrillation during acute phase of ST-segment elevation myocardial infarction.

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

[PMID 28057453] Association of ANRIL gene polymorphisms with major adverse cardiovascular events in hemodialysis patients.

[PMID 28580310OA-icon.png] ANRIL Genetic Variants in Iranian Breast Cancer Patients.

[PMID 28778720] The rs10757278 Polymorphism of the 9p21.3 Locus in Children with Arterial Ischemic Stroke: A Family-Based and Case-Control Study.

[PMID 29722077] ANRIL as a genetic marker for cardiovascular events in renal transplant patients-an observational follow-up cohort study.

[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 31812071] Genetic variants within ANRIL (antisense non coding RNA in the INK4 locus) are associated with risk of psoriasis.