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The C (minor) allele is associated with:

C = Bad version = predictive of APOE4

  • 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 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 [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].

rs429358

Parent Gene: APOE
Importance: 5
Minor Allele: C = 15%
Major Allele: T = 85%
My Genotype: Log In
Risk Allele: C, T, T, C, C, C, C

Disease/Trait: Neuroimaging Measurement

Neuroimaging measurement (P=None)
Risk Allele: None
Reported risk allele frequency: None
Impact:  
Odds Ratio: None 
Reported genes: APOE
Context: missense_variant
Study 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. (R)
Initial sample size: 175 European ancestry Alzheimer cases, 354 European ancestry amnestic mild cognitive impairment cases, 204 European ancestry controls
Replication sample size:
Journal: Neuroimage (R)
Year published: Jan. 22, 2010
Strength of evidence: Strong

Disease/Trait: Cerebral Amyloid Deposition Measurement

Cerebral amyloid deposition measurement (P=8.00*10-32)
Risk Allele: T
Reported risk allele frequency: 2.00%
Impact: 1.10 
Odds Ratio: 0.13 
Reported genes: APOE
Context: missense_variant
Study title: Variations in the FRA10AC1 Fragile Site and 15q21 Are Associated with Cerebrospinal Fluid Aβ1-42 Level. (R)
Initial sample size: up to 883 European and other ancestry individuals
Replication sample size:
Journal: PLoS One (R)
Year published: Aug. 7, 2015
Strength of evidence: Strong

Disease/Trait: High Density Lipoprotein Cholesterol Measurement

High density lipoprotein cholesterol measurement (P=1.00*10-14)
Risk Allele: T
Reported risk allele frequency: 84.00%
Impact: 14.00 
Odds Ratio: 0.066 
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

Disease/Trait: Cerebral Amyloid Deposition Measurement

Cerebral amyloid deposition measurement (P=5.00*10-20)
Risk Allele: C
Reported risk allele frequency: 85.00%
Impact: 9.30 
Odds Ratio: 4.72 
Reported genes: APOE
Context: missense_variant
Study title: Variations in the FRA10AC1 Fragile Site and 15q21 Are Associated with Cerebrospinal Fluid Aβ1-42 Level. (R)
Initial sample size: up to 350 European and other ancestry positive individuals, up to 296 European and other ancestry negative individuals
Replication sample size:
Journal: PLoS One (R)
Year published: Aug. 7, 2015
Strength of evidence: Strong