rs2075650

plus

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

Reference

GRCh38 38.1/141

Chromosome

19

Position

44892362

Gene

TOMM40

is a	snp
is	mentioned by
dbSNP	rs2075650
dbSNP (classic)	rs2075650
ClinGen	rs2075650
ebi	rs2075650
HLI	rs2075650
Exac	rs2075650
Gnomad	rs2075650
Varsome	rs2075650
LitVar	rs2075650
Map	rs2075650
PheGenI	rs2075650
Biobank	rs2075650
1000 genomes	rs2075650
hgdp	rs2075650
ensembl	rs2075650
geneview	rs2075650
scholar	rs2075650
google	rs2075650
pharmgkb	rs2075650
gwascentral	rs2075650
openSNP	rs2075650
23andMe	rs2075650
SNPshot	rs2075650
SNPdbe	rs2075650
MSV3d	rs2075650
GWAS Ctlg	rs2075650

GMAF

0.1336

Max Magnitude

2

?

(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 19668339 ] 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]

A 2020 study has found that rs2075650(G) was found to be associated with high-likelihood Alzheimer's disease cases as when the risk allele was found on an APOE ε3 haplotype. [[https://www.ncbi.nlm.nih.gov/pubmed/24270849 ?dopt=Abstract PMID 24270849 ]]

[PMID 24270849 ] 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 19060911 ]
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 18439552 ]
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 19734902 ]
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 20100581 ]
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 20460622 ]
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 20885792 ] Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities

GWAS snp
PMID	[PMID 20932310 ]
Trait
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 21123754 ]
Trait
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

OMIM	104310
Desc
Variant
Related	also

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 20061627 ]
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 21943158 ]
Trait
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 22445811 ] Genetic variants influencing human aging from late-onset Alzheimer's disease (LOAD) genome-wide association studies (GWAS)

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

[PMID 18262040 ] LDL-cholesterol concentrations: a genome-wide association study.

[PMID 18439548 ] 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 19060910 ] Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.

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

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

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

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

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

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

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

[PMID 21459483 ] Using CSF biomarkers to replicate genetic associations in Alzheimer's disease.

[PMID 21647738 ] 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 22694956 ]
Trait
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

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 23326517 ]
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 23001569 ] 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 23844046 ]
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 24549102 ] TOMM40 rs2075650 May Represent a New Candidate Gene for Vulnerability to Major Depressive Disorder

[PMID 22430674 ] 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 23040522 ] Apolipoprotein E and familial longevity.

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

[PMID 23193196 ] 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 24770881 ]
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 24755620 ]
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 25098835 ] 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.

[PMID 28800603 ] Genetic variants specific to aging-related verbal memory: Insights from GWASs in a population-based cohort.

[PMID 29942042 ] A decade in psychiatric GWAS research.

[PMID 30319691 ] Genome-Wide Association and Mechanistic Studies Indicate That Immune Response Contributes to Alzheimer's Disease Development.

[PMID 31318836 ] An Aging-Related Single-Nucleotide Polymorphism is Associated with Altered Clinical Outcomes and Distinct Inflammatory Profiles in Aged Blunt Trauma Patients.