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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: T, C, C, C, C, C, T

Disease/Trait: High Density Lipoprotein Cholesterol Measurement

Reported risk allele frequency: 84.00%
Reported genes: APOE
Beta coefficient: 0.066 s.d. increase
Risk Allele: T (P=1.00*10-14)
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: Lewy Body Dementia Measurement

Reported risk allele frequency: 73.20%
Reported genes: APOE
Beta coefficient: 0.4997 unit decrease
Risk Allele: C (P=1.00*10-12)
Context: missense_variant
Study title: Genome-Wide Association Meta-analysis of Neuropathologic Features of Alzheimer's Disease and Related Dementias. (R)
Initial sample size: up to 3,526 individuals
Replication sample size:
Journal: PLoS Genet (R)
Year published: Sept. 4, 2014
Strength of evidence: Strong

Disease/Trait: Lewy Body Dementia

Reported risk allele frequency: 73.20%
Reported genes: APOE
Beta coefficient: 0.4997 unit decrease
Risk Allele: C (P=1.00*10-12)
Context: missense_variant
Study title: Genome-Wide Association Meta-analysis of Neuropathologic Features of Alzheimer's Disease and Related Dementias. (R)
Initial sample size: up to 3,526 individuals
Replication sample size:
Journal: PLoS Genet (R)
Year published: Sept. 4, 2014
Strength of evidence: Strong

Disease/Trait: Lewy Body Dementia Measurement

Reported risk allele frequency: 73.47%
Reported genes: APOE
Beta coefficient: 0.508 unit decrease
Risk Allele: C (P=5.00*10-12)
Context: missense_variant
Study title: Genome-Wide Association Meta-analysis of Neuropathologic Features of Alzheimer's Disease and Related Dementias. (R)
Initial sample size: up to 3,526 individuals
Replication sample size:
Journal: PLoS Genet (R)
Year published: Sept. 4, 2014
Strength of evidence: Strong

Disease/Trait: Lewy Body Dementia

Reported risk allele frequency: 73.47%
Reported genes: APOE
Beta coefficient: 0.508 unit decrease
Risk Allele: C (P=5.00*10-12)
Context: missense_variant
Study title: Genome-Wide Association Meta-analysis of Neuropathologic Features of Alzheimer's Disease and Related Dementias. (R)
Initial sample size: up to 3,526 individuals
Replication sample size:
Journal: PLoS Genet (R)
Year published: Sept. 4, 2014
Strength of evidence: Strong

Disease/Trait: T-Tau Measurement

rs429358 is reported to be associated with T-Tau Measurement(R)

Reported risk allele frequency: None
Reported genes: APOE
Risk Allele: None (P=1.00*10-6)
Context: missense_variant
Study title: Genome-wide association study of CSF biomarkers Abeta1-42, t-tau, and p-tau181p in the ADNI cohort. (R)
Initial sample size: 96 European ancestry Alzheimer disease cases, 176 European ancestry individuals with mild cognitive impairment, 102 European ancestry controls
Replication sample size:
Journal: Neurology (R)
Year published: Dec. 1, 2010
Strength of evidence: Strong

Disease/Trait: Alzheimers Disease

rs429358 is reported to be associated with Alzheimers Disease

Reported risk allele frequency: None
Reported genes: APOE
Risk Allele: None (P=1.00*10-6)
Context: missense_variant
Study title: Genome-wide association study of CSF biomarkers Abeta1-42, t-tau, and p-tau181p in the ADNI cohort. (R)
Initial sample size: 96 European ancestry Alzheimer disease cases, 176 European ancestry individuals with mild cognitive impairment, 102 European ancestry controls
Replication sample size:
Journal: Neurology (R)
Year published: Dec. 1, 2010
Strength of evidence: Strong

Disease/Trait: Beta-Amyloid 1-42 Measurement

rs429358 is reported to be associated with Beta-Amyloid 1-42 Measurement(R)

Reported risk allele frequency: None
Reported genes: APOE
Risk Allele: None (P=1.00*10-6)
Context: missense_variant
Study title: Genome-wide association study of CSF biomarkers Abeta1-42, t-tau, and p-tau181p in the ADNI cohort. (R)
Initial sample size: 96 European ancestry Alzheimer disease cases, 176 European ancestry individuals with mild cognitive impairment, 102 European ancestry controls
Replication sample size:
Journal: Neurology (R)
Year published: Dec. 1, 2010
Strength of evidence: Strong

Disease/Trait: P-Tau Measurement

rs429358 is reported to be associated with P-Tau Measurement(R)

Reported risk allele frequency: None
Reported genes: APOE
Risk Allele: None (P=1.00*10-6)
Context: missense_variant
Study title: Genome-wide association study of CSF biomarkers Abeta1-42, t-tau, and p-tau181p in the ADNI cohort. (R)
Initial sample size: 96 European ancestry Alzheimer disease cases, 176 European ancestry individuals with mild cognitive impairment, 102 European ancestry controls
Replication sample size:
Journal: Neurology (R)
Year published: Dec. 1, 2010
Strength of evidence: Strong

Disease/Trait: Neuroimaging Measurement

rs429358 is reported to be associated with Neuroimaging Measurement(R)

Reported risk allele frequency: None
Reported genes: APOE
Risk Allele: None (P=1.00*10-7)
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

Reported risk allele frequency: 85.00%
Reported genes: APOE
Odds ratio: 4.72
Risk Allele: C (P=5.00*10-20)
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

Disease/Trait: Lewy Body Dementia Measurement

Reported risk allele frequency: 73.44%
Reported genes: APOE
Beta coefficient: 0.4905 unit decrease
Risk Allele: C (P=3.00*10-11)
Context: missense_variant
Study title: Genome-Wide Association Meta-analysis of Neuropathologic Features of Alzheimer's Disease and Related Dementias. (R)
Initial sample size: up to 3,526 individuals
Replication sample size:
Journal: PLoS Genet (R)
Year published: Sept. 4, 2014
Strength of evidence: Strong

Disease/Trait: Lewy Body Dementia

Reported risk allele frequency: 73.44%
Reported genes: APOE
Beta coefficient: 0.4905 unit decrease
Risk Allele: C (P=3.00*10-11)
Context: missense_variant
Study title: Genome-Wide Association Meta-analysis of Neuropathologic Features of Alzheimer's Disease and Related Dementias. (R)
Initial sample size: up to 3,526 individuals
Replication sample size:
Journal: PLoS Genet (R)
Year published: Sept. 4, 2014
Strength of evidence: Strong

Disease/Trait: Alzheimers Disease

Reported risk allele frequency: 28.00%
Reported genes: APOE
Risk Allele: C (P=5.00*10-14)
Context: missense_variant
Study title: APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study. (R)
Initial sample size: 555 European ancestry individuals
Replication sample size:
Journal: Mol Psychiatry (R)
Year published: Feb. 19, 2013
Strength of evidence: Strong

Disease/Trait: Amyloid-Beta Measurement

Reported risk allele frequency: 28.00%
Reported genes: APOE
Risk Allele: C (P=5.00*10-14)
Context: missense_variant
Study title: APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study. (R)
Initial sample size: 555 European ancestry individuals
Replication sample size:
Journal: Mol Psychiatry (R)
Year published: Feb. 19, 2013
Strength of evidence: Strong

Disease/Trait: Alzheimers Disease

rs429358 is associated with Alzheimers Disease. It is reported to have a 0.4 unit decrease on Cerebrospinal AB1-42 levels in Alzheimer's disease dementia. No specific risk allele was identified in the study.

Reported risk allele frequency: 44.20%
Reported genes: APOE
Beta coefficient: 0.4 unit decrease
Risk Allele: None (P=4.00*10-17)
Context: missense_variant
Study title: SUCLG2 identified as both a determinator of CSF Aß1-42-levels and an attenuator of cognitive decline in Alzheimer's disease. (R)
Initial sample size: 363 European ancestry individuals
Replication sample size: 515 individuals
Journal: Hum Mol Genet (R)
Year published: July 15, 2014
Strength of evidence: Strong

Disease/Trait: Beta-Amyloid 1-42 Measurement

rs429358 is associated with Beta-Amyloid 1-42 Measurement(R). It is reported to have a 0.4 unit decrease on Cerebrospinal AB1-42 levels in Alzheimer's disease dementia. No specific risk allele was identified in the study.

Reported risk allele frequency: 44.20%
Reported genes: APOE
Beta coefficient: 0.4 unit decrease
Risk Allele: None (P=4.00*10-17)
Context: missense_variant
Study title: SUCLG2 identified as both a determinator of CSF Aß1-42-levels and an attenuator of cognitive decline in Alzheimer's disease. (R)
Initial sample size: 363 European ancestry individuals
Replication sample size: 515 individuals
Journal: Hum Mol Genet (R)
Year published: July 15, 2014
Strength of evidence: Strong

Disease/Trait: Wet Macular Degeneration

rs429358 is associated with Wet Macular Degeneration(R). It is reported to increased association with Advanced age-related macular degeneration (EA). No specific risk allele was identified in the study.

Reported risk allele frequency: None
Reported genes: APOE
Odds ratio: 1.4285715
Risk Allele: None (P=2.00*10-42)
Context: missense_variant
Study title: A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. (R)
Initial sample size: 16,144 European ancestry cases, 17,832 European ancestry controls
Replication sample size: 473 Asian ancestry cases, 1,099 Asian ancestry controls, 52 African ancestry cases, 361 African ancestry cases, 254 other non-European ancestry cases, 694 other non-European ancestry controls
Journal: Nat Genet (R)
Year published: Dec. 21, 2015
Strength of evidence: Strong

Disease/Trait: Age-Related Macular Degeneration

rs429358 is associated with Age-Related Macular Degeneration(R). It is reported to increased association with Advanced age-related macular degeneration (EA). No specific risk allele was identified in the study.

Reported risk allele frequency: None
Reported genes: APOE
Odds ratio: 1.4285715
Risk Allele: None (P=2.00*10-42)
Context: missense_variant
Study title: A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. (R)
Initial sample size: 16,144 European ancestry cases, 17,832 European ancestry controls
Replication sample size: 473 Asian ancestry cases, 1,099 Asian ancestry controls, 52 African ancestry cases, 361 African ancestry cases, 254 other non-European ancestry cases, 694 other non-European ancestry controls
Journal: Nat Genet (R)
Year published: Dec. 21, 2015
Strength of evidence: Strong

Disease/Trait: Atrophic Macular Degeneration

rs429358 is associated with Atrophic Macular Degeneration. It is reported to increased association with Advanced age-related macular degeneration (EA). No specific risk allele was identified in the study.

Reported risk allele frequency: None
Reported genes: APOE
Odds ratio: 1.4285715
Risk Allele: None (P=2.00*10-42)
Context: missense_variant
Study title: A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. (R)
Initial sample size: 16,144 European ancestry cases, 17,832 European ancestry controls
Replication sample size: 473 Asian ancestry cases, 1,099 Asian ancestry controls, 52 African ancestry cases, 361 African ancestry cases, 254 other non-European ancestry cases, 694 other non-European ancestry controls
Journal: Nat Genet (R)
Year published: Dec. 21, 2015
Strength of evidence: Strong

Disease/Trait: Cerebral Amyloid Deposition Measurement

Reported risk allele frequency: 2.00%
Reported genes: APOE
Beta coefficient: 0.13 unit decrease
Risk Allele: T (P=8.00*10-32)
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: Cognitive Decline

rs429358 is associated with Cognitive Decline(R). It is reported to have a 0.01 unit decrease on Cognitive decline (age-related). No specific risk allele was identified in the study.

Reported risk allele frequency: None
Reported genes: APOE
Beta coefficient: 0.01 unit decrease
Risk Allele: None (P=2.00*10-14)
Context: missense_variant
Study title: Genetic architecture of age-related cognitive decline in African Americans. (R)
Initial sample size: 3,964 African American ancestry individuals.
Replication sample size:
Journal: Neurol Genet (R)
Year published: Dec. 21, 2016
Strength of evidence: Strong

Disease/Trait: Neuroimaging Measurement

rs429358 is reported to be associated with Neuroimaging Measurement(R)

Reported risk allele frequency: None
Reported genes: APOE
Risk Allele: None (P=1.00*10-9)
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: Blood Protein Measurement

rs429358 is reported to be associated with Blood Protein Measurement

Reported risk allele frequency: None
Reported genes: APOE
Risk Allele: None (P=2.00*10-12)
Context: missense_variant
Study title: Connecting genetic risk to disease end points through the human blood plasma proteome. (R)
Initial sample size: 997 European ancestry individuals
Replication sample size: 338 Arab, South Asian and Filipino ancestry individuals
Journal: Nat Commun (R)
Year published: Feb. 27, 2017
Strength of evidence: Strong