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From SNPedia

Geno Mag Summary
(A;A) 2.1 1.2x risk of coronary artery disease
Make rs646776(A;G)
Make rs646776(G;G)
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
1000 genomesrs646776
23andMe allrs646776
SNP Nexus

GWAS Ctlgrs646776
Max Magnitude2.1
? (A;A) (A;G) (G;G) 28
[PMID 18262040OA-icon.png] rs599839 and rs4970834 explain about 1% of the variation in circulating LDL-cholesterol levels. "When we look at this particular genetic variance, of all the cholesterol variation among the population, 1% of it can be attributed to this particular locus," said Sandhu. "This is equivalent to more established genes for LDL regulation, particularly APOE." rs646776 also linked.

Pharmacogenetic meta-analysis of genome-wide association studies of LDL ​cholesterol response to statins found each minor allele to increase statin effectiveness by 1.3% (rs646776, β=−0.013, s.e.=0.002, P=1.05 × 10−9 and rs12740374, β=−0.013, s.e.=0.002, P=1.05 × 10−9).

23andMe blog coronary artery disease and heart attack

SNP Risk Version Effect

SNP rs646776
PubMedID [PMID 18193044OA-icon.png]
Condition LDL cholesterol
Risk Allele C
pValue 3.00E-029
OR 0.16
95% CI 0.14-0.18) % SD lowe

[PMID 19380133] Significant impact of chromosomal locus 1p13.3 on serum LDL cholesterol and on angiographically characterized coronary atherosclerosis

GWAS snp
PMID [PMID 19198609OA-icon.png]
Trait Myocardial infarction (early onset)
Title Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants
Risk Allele T
P-val 8E-12
Odds Ratio 1.19 [1.13-1.26]
GWAS snp
PMID [PMID 19060911OA-icon.png]
Trait Cholesterol, total
Title Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
Risk Allele G
P-val 9E-22
Odds Ratio 0.13 [NR] SD decrease
GWAS snp
PMID [PMID 19060910OA-icon.png]
Trait LDL cholesterol
Title Genome-wide association analysis of metabolic traits in a birth cohort from a founder population
Risk Allele G
P-val 2E-12
Odds Ratio 0.16 [0.11-0.20] mmol/l decrease

GWAS snp
PMID [PMID 20339536OA-icon.png]
Trait Response to statin therapy
Title Genome-wide association of lipid-lowering response to statins in combined study populations
Risk Allele C
P-val 0.000004
Odds Ratio None None

[PMID 21087763OA-icon.png] Genome-wide screen identifies rs646776 near sortilin as a regulator of progranulin levels in human plasma

GWAS snp
PMID [PMID 21378988]
Title A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
Risk Allele T
P-val 6E-10
Odds Ratio 1.1400 [1.09-1.19]

[PMID 18179892OA-icon.png] Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia.

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

[PMID 19060906OA-icon.png] Common variants at 30 loci contribute to polygenic dyslipidemia.

[PMID 19185284OA-icon.png] Common variation in the beta-carotene 15,15'-monooxygenase 1 gene affects circulating levels of carotenoids: a genome-wide association study.

[PMID 19299407OA-icon.png] Replication of genetic associations with plasma lipoprotein traits in a multiethnic sample.

[PMID 19435741OA-icon.png] Common lipid-altering gene variants are associated with therapeutic intervention thresholds of lipid levels in older people.

[PMID 19679263OA-icon.png] Using new tools to define the genetic underpinnings of risky traits associated with coronary artery disease: the SardiNIA study.

[PMID 19951432OA-icon.png] Analysis of recently identified dyslipidemia alleles reveals two loci that contribute to risk for carotid artery disease.

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

[PMID 20084173OA-icon.png] Magnitude of stratification in human populations and impacts on genome wide association studies.

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

[PMID 20570915] Genetic determinants of major blood lipids in Pakistanis compared with Europeans.

[PMID 20832063] Exploring genetic determinants of plasma total cholesterol levels and their predictive value in a longitudinal study.

[PMID 20835900OA-icon.png] Genetics of diabetes complications.

[PMID 21242481OA-icon.png] Genetic risk score and risk of myocardial infarction in Hispanics.

[PMID 21297524OA-icon.png] The 1p13.3 LDL (C)-associated locus shows large effect sizes in young populations.

[PMID 22152955OA-icon.png] Genetic susceptibility to coronary heart disease in type 2 diabetes: 3 independent studies.

GET Evidence
impact pathogenic
qualified_impact Insufficiently evaluated pathogenic
overall_frequency 0.78125

[PMID 23098650] Impact of variants within seven candidate genes on statin treatment efficacy

[PMID 24622110OA-icon.png] Multi-Ancestral Analysis of Inflammation-Related Genetic Variants and C-Reactive Protein in the Population Architecture using Genomics and Epidemiology (PAGE) Study

[PMID 23092954OA-icon.png] SHAVE: shrinkage estimator measured for multiple visits increases power in GWAS of quantitative traits.

[PMID 23100282OA-icon.png] Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.

[PMID 23398167] Reduced serum progranulin level might be associated with Parkinson's disease risk.

GWAS snp
PMID [PMID 19936222OA-icon.png]
Trait Lipid metabolism phenotypes
Title Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis.
Risk Allele
P-val 2E-53
Odds Ratio 5.21 [NR] unit decrease

[PMID 27329260] Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits.