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From SNPedia

Geno Mag Summary
(A;A) 0 normal; some association with greater longevity
(A;G) 2 possibly 2x higher Alzheimer's risk
(G;G) 2 possibly 4x higher Alzheimer's risk
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
1000 genomesrs2075650
23andMe allrs2075650
SNP Nexus

GWAS Ctlgrs2075650
Max Magnitude2
? (A;A) (A;G) (G;G) 28

Located close to ApoE4, yet may independently (also) influence risk of Alzheimer's disease.

A case-control study of 381 patients found a 2x higher risk for Alzheimer's disease associated with the rarer rs2075650(G) allele. 10.1371/journal.pone.0006501

This allele is associated with earlier onset of Alzheimer's disease, by ~7 years. (news) [PMID 19668339OA-icon.png] The data from this study are available online at [1]. The association of this SNP with late-onset Alzheimer's disease was confirmed by a study reported in PLoS Genetics.

The A allele of this SNP is one of 150 identified as relevant to exceptional longevity in 10.1126/science.1190532

Recent work suggests, however, that the linkage disequilibrium between rs2075650 and the ApoE ε4 defining SNP rs429358 means that there may be little, if any, independent effect of rs2075650 on Alzheimer's risk. [2]

[PMID 24270849OA-icon.png] rs2075650 was found to be associated with Alzheimer's disease based on a study by the eMERGE network in which electronic medical records were searched to find clinical associations associated with selected SNPs.

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 3E-19
Odds Ratio 0.14 [NR] SD increase
GWAS snp
PMID [PMID 18439552OA-icon.png]
Trait C-reactive protein
Title Polymorphisms of the HNF1A Gene Encoding Hepatocyte Nuclear Factor-1 Alpha are Associated with C-Reactive Protein
Risk Allele
P-val 9.9999999999999995E-8
Odds Ratio NR NR
GWAS snp
PMID [PMID 19749422]
Trait Alzheimer's Disease
Title Genome-Wide Scan of Copy Number Variation in Late-Onset Alzheimer's Disease
Risk Allele
P-val 3E-11
Odds Ratio NR NR
GWAS snp
PMID [PMID 19734902OA-icon.png]
Trait Alzheimer's disease
Title Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease
Risk Allele
P-val 0
Odds Ratio 2.53 [2.37-2.71]
GWAS snp
PMID [PMID 19734903]
Trait Alzheimer's disease
Title Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease
Risk Allele
P-val 2E-16
Odds Ratio NR NR

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
GWAS snp
PMID [PMID 20460622OA-icon.png]
Trait Alzheimer's disease
Title Genome-wide Analysis of Genetic Loci Associated with Alzheimer Disease
Risk Allele G
P-val 0
Odds Ratio 2.53 [2.41-2.66]

[PMID 20885792OA-icon.png] Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities

GWAS snp
PMID [PMID 20932310OA-icon.png]
Title Genome-wide association reveals genetic effects on human Abeta42 and tau protein levels in cerebrospinal fluids: a case control study
Risk Allele G
P-val 3E-7
Odds Ratio None None
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
GWAS snp
PMID [PMID 20595579]
Trait Longevity
Title Genetic Signatures of Exceptional Longevity in Humans.
Risk Allele A
P-val 8E-12
Odds Ratio 2.0800 [NR]
GWAS snp
PMID [PMID 20061627OA-icon.png]
Trait Alzheimer's disease
Title Genome-wide scan of copy number variation in late-onset Alzheimer's disease.
Risk Allele
P-val 3E-11
Odds Ratio None None
GWAS snp
PMID [PMID 21943158OA-icon.png]
Title Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits.
Risk Allele G
P-val 2E-14
Odds Ratio 0.1530 [0.11-0.19] mmol/l increase

[PMID 22445811OA-icon.png] Genetic variants influencing human aging from late-onset Alzheimer's disease (LOAD) genome-wide association studies (GWAS)

[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 18262040OA-icon.png] LDL-cholesterol concentrations: a genome-wide association study.

[PMID 18439548OA-icon.png] Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study.

[PMID 19060910OA-icon.png] Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.

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

[PMID 19197348OA-icon.png] Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.

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

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

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

[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 21459483OA-icon.png] Using CSF biomarkers to replicate genetic associations in Alzheimer's disease.

[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.

GWAS snp
PMID [PMID 22694956OA-icon.png]
Title Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3.
Risk Allele A
P-val 8E-8
Odds Ratio 1.3700 None

GET Evidence
impact pathogenic
qualified_impact Insufficiently evaluated pathogenic
overall_frequency 0.131995

GWAS snp
PMID [PMID 23207651]
Trait Cognitive decline
Title A genome-wide association study implicates the APOE locus in nonpathological cognitive ageing.
Risk Allele G
P-val 2E-8
Odds Ratio .20 [0.12-0.28] unit decrease
GWAS snp
PMID [PMID 23326517OA-icon.png]
Trait Age-related macular degeneration
Title Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis.
Risk Allele A
P-val 1E-6
Odds Ratio 1.23 [1.13-1.34]

[PMID 23001569OA-icon.png] Gene-centric meta-analyses of 108 912 individuals confirm known body mass index loci and reveal three novel signals

[PMID 23288655] Association of TOMM40 polymorphisms with late-onset Alzheimer's disease in a Northern Han Chinese population

GWAS snp
PMID [PMID 23844046OA-icon.png]
Trait C-reactive protein
Title Are C-reactive protein associated genetic variants associated with serum levels and retinal markers of microvascular pathology in Asian populations from Singapore?
Risk Allele G
P-val 2E-21
Odds Ratio .12 [NR] unit increase

[PMID 24549102OA-icon.png] TOMM40 rs2075650 May Represent a New Candidate Gene for Vulnerability to Major Depressive Disorder

[PMID 22430674OA-icon.png] Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease.

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

[PMID 23040522OA-icon.png] Apolipoprotein E and familial longevity.

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

[PMID 23193196OA-icon.png] Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimer's disease, multiple sclerosis and endometriosis.

[PMID 23546992] TOMM40 polymorphisms in Italian Alzheimer's disease and frontotemporal dementia patients.

[PMID 24788522] Genetic variation at the CELF1 (CUGBP, elav-like family member 1 gene) locus is genome-wide associated with Alzheimer's disease and obesity

[PMID 25304313] No evidence of association between variant rs2075650 in lipid metabolism-related locus APOE/TOMM40 and advanced age-related macular degeneration in Han Chinese population

GWAS snp
PMID [PMID 24770881OA-icon.png]
Trait Alzheimer's disease
Title ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology.
Risk Allele
P-val 4E-13
Odds Ratio NR NR
GWAS snp
PMID [PMID 24755620OA-icon.png]
Trait Alzheimer's disease
Title Overrepresentation of glutamate signaling in Alzheimer's disease: network-based pathway enrichment using meta-analysis of genome-wide association studies.
Risk Allele G
P-val 9E-116
Odds Ratio 4.48 [NR]

[PMID 25670335] Association of Alzheimer's disease GWAS loci with MRI markers of brain aging

[PMID 25711031] [TOMM40 gene polymorphism association with lipid profile]

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

[PMID 26543236] Risk prediction for sporadic Alzheimer's disease using genetic risk score in the Han Chinese population

[PMID 27550749] Genetic risk score Mendelian randomization shows that obesity measured as body mass index, but not waist:hip ratio, is causal for endometrial cancer.

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