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The Major "C" allele is associated with:

Alzheimer's Disease

CC = Bad version = contributes to APOE4 when combined with CC or CT genotype for rs429358.

  • rs429358 (C;C) + rs7412 (C;C) = APOE4/APOE4 (Bad) = 12x for late-onset Alzheimer's and 61x for early-onset disease [R].

  • rs429358 (C;T) + rs7412 (C;C) = APOE4/APOE3 (Bad) = >3x increased risk for Alzheimer's; 1.4x increased risk for heart disease  [R].

  • rs429358 (T;T) + rs7412 (C;C) = APOE3/APOE3 (Good)

  • If the allele of this SNP is "C" and the same chromosome also harbors the rs429358 "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 rs429358 (C;C) and rs7412 (C;C) individuals, compared to the more common rs429358 (T;T) and rs7412 (C;C) (ApoE3/ApoE3) homozygotes, to be 12x for late-onset Alzheimer's and 61x for early-onset disease [R]. 

  • 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) [R].

 

The Minor "T" allele is associated with:

Decreased Alzheimer's risk.

  • When rs7412 and rs429358 are both T (for the two SNPs located on the same chromosome) this is known as the APOE2 allele. APOE2 indicates a reduced risk of Alzheimer's disease.

rs7412

Parent Gene: APOE
Importance: 5
Minor Allele: T = 8%
Major Allele: C = 92%
My Genotype: Log In
Risk Allele: T, T, C

Disease/Trait: Lipid Measurement

Lipid measurement (P=3.00*10-58)
Risk Allele: None
Reported risk allele frequency: None
Impact: 7.52 
Odds Ratio: 0.75 
Reported genes: APOE
Context: missense_variant
Study title: Genome-wide association study identifies multiple loci influencing human serum metabolite levels. (R)
Initial sample size: 8,330 European ancestry individuals
Replication sample size:
Journal: Nat Genet (R)
Year published: Jan. 29, 2012
Strength of evidence: Strong

Disease/Trait: Response To Statin

Response to statin (P=2.00*10-47)
Risk Allele: None
Reported risk allele frequency: None
Impact: 6.70 
Odds Ratio: 6.2 
Reported genes: APOE
Context: missense_variant
Study title: Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction: the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. (R)
Initial sample size: 6,989 European ancestry individuals
Replication sample size:
Journal: Circ Cardiovasc Genet (R)
Year published: Feb. 13, 2012
Strength of evidence: Strong

Disease/Trait: Low Density Lipoprotein Cholesterol Measurement

Low density lipoprotein cholesterol measurement (P=2.00*10-9)
Risk Allele: None
Reported risk allele frequency: 10.00%
Impact: 8.70 
Odds Ratio: 2.3 
Reported genes: APOE
Context: missense_variant
Study title: High density GWAS for LDL cholesterol in African Americans using electronic medical records reveals a strong protective variant in APOE. (R)
Initial sample size: 1,249 African American individuals
Replication sample size:
Journal: Clin Transl Sci (R)
Year published: Aug. 23, 2012
Strength of evidence: Strong

Disease/Trait: Total Cholesterol Measurement

Total cholesterol measurement (P=2.00*10-30)
Risk Allele: T
Reported risk allele frequency: 12.00%
Impact: 9.70 
Odds Ratio: 0.09 
Reported genes: APOE
Context: missense_variant
Study title: Genetic association with lipids in Filipinos: waist circumference modifies an APOA5 effect on triglyceride levels. (R)
Initial sample size: 1,782 Filipino ancestry mothers
Replication sample size: 1,719 Filipino ancestry offsprings
Journal: J Lipid Res (R)
Year published: Sept. 10, 2013
Strength of evidence: Strong

Disease/Trait: Low Density Lipoprotein Cholesterol Measurement

Low density lipoprotein cholesterol measurement (P=3.00*10-53)
Risk Allele: T
Reported risk allele frequency: 12.00%
Impact: 2.52 
Odds Ratio: 0.48 
Reported genes: APOE
Context: missense_variant
Study title: Genetic association with lipids in Filipinos: waist circumference modifies an APOA5 effect on triglyceride levels. (R)
Initial sample size: 1,782 Filipino ancestry mothers
Replication sample size: 1,719 Filipino ancestry offsprings
Journal: J Lipid Res (R)
Year published: Sept. 10, 2013
Strength of evidence: Strong

Disease/Trait: Total Cholesterol Measurement

Total cholesterol measurement (P=8.00*10-239)
Risk Allele: C
Reported risk allele frequency: 93.00%
Impact: 8.10 
Odds Ratio: 0.413 
Reported genes: APOE
Context: missense_variant
Study title: The impact of low-frequency and rare variants on lipid levels. (R)
Initial sample size: up to 62,166 European ancestry individuals
Replication sample size:
Journal: Nat Genet (R)
Year published: May 11, 2015
Strength of evidence: Strong