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From SNPedia

Geno Mag Summary
(C;C) 1.2 one of 2 snps relevant to classifying APOE genotype
(C;T) >3x increased risk for Alzheimer's; 1.4x increased risk for heart disease
(T;T) 0 common
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
dbSNP (classic)rs429358
1000 genomesrs429358
GWAS Ctlgrs429358
Max Magnitude1.2
? (C;C) (C;T) (T;T) 28

This SNP, located in the fourth exon of the ApoE gene, affects the amino acid at position 130 of the resulting protein. The more common rs429358 allele is (T). If the allele is (C) and the same chromosome also harbors the rs7412(C) allele, the combination is known as an APOE-ε4 allele. The APOE-ε4 allele has a strong influence on the risk of Alzheimer's disease.

Many studies have estimated the level of risk, and it varies depending on age, sex, ethnicity, and other factors. One meta-analysis estimated the odds ratios for homozygous rs429358(C;C) individuals compared to the more common ApoE3/ApoE3 homozygotes to be 12x for late-onset Alzheimer's and 61x for early-onset disease. [PMID 10325447]

Meta-analyses have also supported the association between the APOE-ε4 allele and somewhat increased risk for heart disease, with an odds ratio of 1.42 (CI: 1.26 - 1.61).[15488874?dopt=Abstract PMID 15488874]

Note: Although ApoE status is technically defined by these two SNPs, rs429358 and rs7412, a SNP in the adjacent ApoC1 gene, rs4420638, is co-inherited with ApoE and thus often - though not completely - predictive of it.


[PMID 19818961OA-icon.png] Apolipoprotein E genotype is associated with serum C-reactive protein but not abdominal aortic aneurysm

GWAS snp
PMID [PMID 20100581OA-icon.png]
Trait Brain imaging
Title Whole Genome Association Study of Brain-Wide Imaging Phenotypes for Identifying Quantitative Trait Loci in MCI and AD: A Study of the ADNI Cohort
Risk Allele
P-val NS
Odds Ratio None None

[PMID 20406466OA-icon.png] Genetic variants associated with fasting blood lipids in the U.S. population: Third National Health and Nutrition Examination Survey

[PMID 20429872OA-icon.png] Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

[PMID 20822524OA-icon.png] Isoform of APOE with retained intron 3; quantitation and identification of an associated single nucleotide polymorphism

[PMID 20946940] Association of variants within APOE; SORL1; RUNX1; BACE1 and ALDH18A1 with dementia in Alzheimer's disease in subjects with Down syndrome

[PMID 21263195] An APOE Haplotype Associated with Decreased ?4 Expression Increases the Risk of Late Onset Alzheimer's Disease

GWAS snp
PMID [PMID 21123754OA-icon.png]
Title Genome-wide association study of CSF biomarkers A{beta}1-42, t-tau, and p-tau181p in the ADNI cohort.
Risk Allele
P-val 0.000001
Odds Ratio None None

[PMID 22174202] Apolipoprotein E Gene Polymorphisms Are Strong Predictors of Inflammation and Dyslipidemia in Rheumatoid Arthritis

Risk Rs429358(C;C)
Alt Rs429358(C;C)
Reference Rs429358(T;T)
Significance Other
Disease Familial type 3 hyperlipoproteinemia Alzheimer disease 2 APOE4(-)-FREIBURG APOE4 VARIANT not provided
Variation info
CLNDBN Familial type 3 hyperlipoproteinemia Alzheimer disease 2 APOE4(-)-FREIBURG APOE4 VARIANT not provided
Reversed 0
HGVS NC_000019.9:g.45411941T>C
CLNSRC OMIM Allelic Variant UniProtKB (protein)
CLNACC RCV000019438.29, RCV000019448.31, RCV000019455.29, RCV000019456.28, RCV000019458.24, RCV000292119.1,

[PMID 15113403OA-icon.png] Current limitations of SNP data from the public domain for studies of complex disorders: a test for ten candidate genes for obesity and osteoporosis.

[PMID 15157284OA-icon.png] Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes.

[PMID 16603077OA-icon.png] Variation at APOE and STH loci and Alzheimer's disease.

[PMID 17048007OA-icon.png] Association of warfarin dose with genes involved in its action and metabolism.

[PMID 17356695OA-icon.png] Variation in GYS1 interacts with exercise and gender to predict cardiovascular mortality.

[PMID 17357073OA-icon.png] Genetic analysis of 103 candidate genes for coronary artery disease and associated phenotypes in a founder population reveals a new association between endothelin-1 and high-density lipoprotein cholesterol.

[PMID 17434289OA-icon.png] Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer's disease: patterns of linkage disequilibrium and disease/marker association.

[PMID 17456829OA-icon.png] Evaluation of genetic factors for warfarin dose prediction.

[PMID 17672902OA-icon.png] Subarachnoid hemorrhage: tests of association with apolipoprotein E and elastin genes.

[PMID 17903299OA-icon.png] A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study.

[PMID 18034366] Lack of replication of genetic associations with human longevity.

[PMID 18196181OA-icon.png] Correction of population stratification in large multi-ethnic association studies.

[PMID 18216863OA-icon.png] Genetic determinants of basal C-reactive protein expression in Filipino systemic lupus erythematosus families.

[PMID 18254975OA-icon.png] Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat.

[PMID 18275964OA-icon.png] Low-density lipoprotein and high-density lipoprotein cholesterol levels in relation to genetic polymorphisms and menopausal status: the Atherosclerosis Risk in Communities (ARIC) Study.

[PMID 18378515OA-icon.png] APOE/C1/C4/C2 hepatic control region polymorphism influences plasma apoE and LDL cholesterol levels.

[PMID 18448515OA-icon.png] Evidence that the gene encoding insulin degrading enzyme influences human lifespan.

[PMID 18513389OA-icon.png] New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.

[PMID 18574025OA-icon.png] The largest prospective warfarin-treated cohort supports genetic forecasting.

[PMID 18596683OA-icon.png] Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans.

[PMID 18603647OA-icon.png] Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response.

[PMID 18678618OA-icon.png] Comprehensive association study of type 2 diabetes and related quantitative traits with 222 candidate genes.

[PMID 18823527OA-icon.png] A genome-wide association study for late-onset Alzheimer's disease using DNA pooling.

[PMID 18974842OA-icon.png] Gender differences in genetic risk profiles for cardiovascular disease.

[PMID 18976728OA-icon.png] Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE.

[PMID 19001172OA-icon.png] Analyses of the National Institute on Aging Late-Onset Alzheimer's Disease Family Study: implication of additional loci.

[PMID 19014573OA-icon.png] Application of two machine learning algorithms to genetic association studies in the presence of covariates.

[PMID 19058936OA-icon.png] A polymorphism of apolipoprotein E (APOE) gene is associated with age at natural menopause in Caucasian females.

[PMID 19118814OA-icon.png] Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease.

[PMID 19131662OA-icon.png] A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.

[PMID 19262956] GAB2 gene does not modify the risk of Alzheimer's disease in Spanish APOE 4 carriers.

[PMID 19263529OA-icon.png] Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.

[PMID 19285141OA-icon.png] Genetic determinants of target and novelty-related event-related potentials in the auditory oddball response.

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

[PMID 19336475OA-icon.png] Integrated associations of genotypes with multiple blood biomarkers linked to coronary heart disease risk.

[PMID 19377787] Association between apolipoprotein E genotype, serum lipids, and colorectal cancer in Brazilian individuals.

[PMID 19541455] Apolipoprotein-E gene variants associated with cardiovascular risk factors in antipsychotic recipients.

[PMID 19667110] Identification of genetic variants associated with response to statin therapy.

[PMID 19668339OA-icon.png] Hippocampal atrophy as a quantitative trait in a genome-wide association study identifying novel susceptibility genes for Alzheimer's disease.

[PMID 19734902OA-icon.png] Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease.

[PMID 19756043OA-icon.png] A simple and efficient algorithm for genome-wide homozygosity analysis in disease.

[PMID 19787382OA-icon.png] Introduction to the DISRUPT postprandial database: subjects, studies and methodologies.

[PMID 19913121OA-icon.png] Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.

[PMID 19936222OA-icon.png] Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis.

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

[PMID 20082485OA-icon.png] Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women.

[PMID 20167577OA-icon.png] Analysis of lipid pathway genes indicates association of sequence variation near SREBF1/TOM1L2/ATPAF2 with dementia risk.

[PMID 20396431OA-icon.png] Genotyping sleep disorders patients.

[PMID 20451875OA-icon.png] Alzheimer's Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans.

[PMID 20565774OA-icon.png] Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.

[PMID 20663622] A susceptible haplotype within APOE gene influences BMD and intensifies the osteoporosis risk in postmenopausal women of Northwest India.

[PMID 20682755OA-icon.png] A pilot study of gene/gene and gene/environment interactions in Alzheimer disease.

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

[PMID 21215387OA-icon.png] IQ, educational attainment, memory and plasma lipids: associations with apolipoprotein E genotype in 5995 children.

[PMID 21228733OA-icon.png] Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients.

[PMID 21285406] Low-density lipoprotein cholesterol and the risk of cancer: a mendelian randomization study.

[PMID 21324458OA-icon.png] Association of gene variants with lipid levels in response to fenofibrate is influenced by metabolic syndrome status.

[PMID 21379329OA-icon.png] Genome-wide association of familial late-onset Alzheimer's disease replicates BIN1 and CLU and nominates CUGBP2 in interaction with APOE.

[PMID 21418511OA-icon.png] Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited.

[PMID 21647738OA-icon.png] Genome-wide association with C-reactive protein levels in CLHNS: evidence for the CRP and HNF1A loci and their interaction with exposure to a pathogenic environment.

[PMID 21689001] Association study between apolipoprotein E gene polymorphism and diabetic nephropathy in a Taiwanese population.

[PMID 21703254] APOE haplotypes are associated with human longevity in a Central Italy population: evidence for epistasis with HP 1/2 polymorphism.

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

[PMID 22234866OA-icon.png] Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity.

[PMID 23571587OA-icon.png] Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans

GWAS snp
PMID [PMID 23419831OA-icon.png]
Trait Alzheimer's disease biomarkers
Title APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study.
Risk Allele C
P-val 5E-14
Odds Ratio NR NR

[PMID 24291031] Association of APOE, GCPII and MMP9 polymorphisms with common diseases and lipid levels in an older adult/elderly cohort

[PMID 22651940] The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case-control cohorts.

[PMID 22710912] TOMM40, APOE, and APOC1 in primary progressive aphasia and frontotemporal dementia.

[PMID 22898894] Pleiotropy and allelic heterogeneity in the TOMM40-APOE genomic region related to clinical and metabolic features of hepatitis C infection.

[PMID 22922093] Low-density lipoprotein cholesterol and risk of gallstone disease: a Mendelian randomization study and meta-analyses.

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

[PMID 23207651OA-icon.png] A genome-wide association study implicates the APOE locus in nonpathological cognitive ageing.

[PMID 23533563OA-icon.png] Novel risk factors for premature peripheral arterial occlusive disease in non-diabetic patients: a case-control study.

[PMID 25085564OA-icon.png] Influence of multiple

[PMID 25098835OA-icon.png] Longitudinal analysis is more powerful than cross-sectional analysis in detecting genetic association with neuroimaging phenotypes

[PMID 26043189] Genetic determinants of quantitative traits associated with cardiovascular disease risk

[PMID 26175754OA-icon.png] DNA methylation and single nucleotide variants in the brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) genes are associated with anxiety/depression in older women

[PMID 26405973] Gene environment interaction of GALNT2 and APOE gene with hypertension in the Chinese Han Population

[PMID 26404360OA-icon.png] Effects of APOE rs429358, rs7412 and GSTM1/GSTT1 Polymorphism on Plasma and Erythrocyte Antioxidant Parameters and Cognition in Old Chinese Adults

[PMID 25545672] Apolipoprotein E gene polymorphisms in relation to chronic periodontitis, periodontopathic bacteria, and lipid levels

[PMID 27277494OA-icon.png] Identifying Multimodal Intermediate Phenotypes Between Genetic Risk Factors and Disease Status in Alzheimer's Disease.

[PMID 27585988OA-icon.png] Structured sparse CCA for brain imaging genetics via graph OSCAR.

[PMID 27707806OA-icon.png] Replication of Genome-Wide Association Study Findings of Longevity in White, African American, and Hispanic Women: The Women's Health Initiative.

[PMID 28189700OA-icon.png] CSF protein changes associated with hippocampal sclerosis risk gene variants highlight impact of GRN/PGRN.

[PMID 28480219OA-icon.png] Apolipoprotein E Genotype in Very Preterm Neonates with Intrauterine Growth Restriction: An Analysis of the German Neonatal Network Cohort.

[PMID 28983317OA-icon.png] Genetic Analysis of Mitochondrial Ribosomal Proteins and Cognitive Aging in Postmenopausal Women.

[PMID 29532745] Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis.

[PMID 31833563] A novel multi-locus genetic risk score identifies patients with higher risk of generalized aggressive periodontitis.

[PMID 32622117] Trace elements and APOE polymorphisms in pregnant women and their new-borns.

[PMID 32647408OA-icon.png] Association of Common Single Nucleotide Polymorphisms of Candidate Genes with Gallstone Disease: A Meta-Analysis.

[PMID 33163038OA-icon.png] Lack of association between genetic variants in the 19q13.32 region and CHD risk in the Algerian population: a population-based nested case-control study.

[PMID 33204816OA-icon.png] Haplotype architecture of the Alzheimer's risk in the APOE region via co-skewness.