{{Rsnum
|rsid=2075650
|Gene=TOMM40
|Chromosome=19
|position=44892362
|Orientation=plus
|GMAF=0.1336
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=TOMM40
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 71.7 | 24.8 | 3.5
| HCB | 77.4 | 21.9 | 0.7
| JPT | 79.6 | 19.5 | 0.9
| YRI | 74.8 | 21.1 | 4.1
| ASW | 73.7 | 22.8 | 3.5
| CHB | 77.4 | 21.9 | 0.7
| CHD | 82.6 | 15.6 | 1.8
| GIH | 78.2 | 18.8 | 3.0
| LWK | 67.3 | 30.9 | 1.8
| MEX | 77.6 | 22.4 | 0.0
| MKK | 80.1 | 19.2 | 0.6
| TSI | 82.2 | 16.8 | 1.0
| HapMapRevision=28
}}

Located close to [[ApoE4]], yet independently (also) influences 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. {{doi|10.1371/journal.pone.0006501}}

This allele is associated with earlier onset of Alzheimer's disease, by ~7 years. ([http://www.genengnews.com/news/bnitem.aspx?name=59871915 news]) {{PMID|19668339|OA=1
}} The data from this study are available online at [http://www.loni.ucla.edu/ADNI/Data/]. The association of this SNP with late-onset [[Alzheimer's disease]] was confirmed by a study reported in [http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1001130 PLoS Genetics].

The A allele of this SNP is one of 150 identified as relevant to exceptional [[longevity]] in {{doi|10.1126/science.1190532}}

{{PMID|24270849|OA=1
}} [[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.

{{PMID Auto GWAS
|PMID=19060911
|Trait=Cholesterol, total
|Title=Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
|RiskAllele=G
|Pval=3E-19
|OR=0.14
|ORtxt=[NR] SD increase
|OA=1
}}
{{PMID Auto GWAS
|PMID=18439552
|Trait=C-reactive protein
|Title=Polymorphisms of the HNF1A Gene Encoding Hepatocyte Nuclear Factor-1 Alpha are Associated with C-Reactive Protein
|RiskAllele=
|Pval=9.9999999999999995E-8
|OR=NR
|ORtxt=NR
|OA=1
}}

{{PMID Auto GWAS
|PMID=19749422
|Trait=Alzheimer's Disease
|Title=Genome-Wide Scan of Copy Number Variation in Late-Onset Alzheimer's Disease
|RiskAllele=
|Pval=3E-11
|OR=NR
|ORtxt=NR
}}
{{PMID Auto GWAS
|PMID=19734902
|Trait=Alzheimer's disease
|Title=Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease
|RiskAllele=
|Pval=0
|OR=2.53
|ORtxt=[2.37-2.71]
|OA=1
}}
{{PMID Auto GWAS
|PMID=19734903
|Trait=Alzheimer's disease
|Title=Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease
|RiskAllele=
|Pval=2E-16
|OR=NR
|ORtxt=NR
}}

{{PharmGKB
|RSID=rs2075650
|Name_s=
|Gene_s=TOMM40
|Feature=
|Evidence=PubMed ID:19060911; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. (Initial Sample Size: 22,562 individuals; Replication Sample Size: NR); (Region: 19q13.32; Reported Gene(s): TOMM40, APOE; Risk Allele: rs2075650-G); (p-value= 3E-19).This variant is associated with Cholesterol, total.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740195
}}

{{PMID Auto GWAS
|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
|RiskAllele=
|Pval=NS
|OR=None
|ORtxt=None
|OA=1
}}

{{PMID Auto GWAS
|PMID=20460622
|Trait=Alzheimer's disease
|Title=Genome-wide Analysis of Genetic Loci Associated with Alzheimer Disease
|RiskAllele=G
|Pval=0
|OR=2.53
|ORtxt=[2.41-2.66]
|OA=1
}}
{{PMID Auto
|PMID=20885792
|Title=Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities
|OA=1
}}

{{PharmGKB
|RSID=rs2075650
|Name_s=
|Gene_s=TOMM40
|Feature=
|Evidence=PubMed ID:18439552
|Annotation=In a GWAS of subjects from the PARC study (Pharmacogenomics and Risk of Cardiovascular Disease), this was one of the ten SNPs most strongly associated with plasma C-reactive protein levels.
|Drugs=
|Drug Classes=
|Diseases=Cardiovascular Diseases
|Curation Level=Curated
|PharmGKB Accession ID=PA162399728
}}
{{PMID Auto GWAS
|PMID=20932310
|Trait=None
|Title=Genome-wide association reveals genetic effects on human Abeta42 and tau protein levels in cerebrospinal fluids: a case control study
|RiskAllele=G
|Pval=3E-7
|OR=None
|ORtxt=None
|OA=1
}}

{{PMID Auto GWAS
|PMID=21123754
|Trait=None
|Title=Genome-wide association study of CSF biomarkers A{beta}1-42, t-tau, and p-tau181p in the ADNI cohort.
|RiskAllele=
|Pval=0.000001
|OR=None
|ORtxt=None
|OA=1
}}
{{omim
|id=104310
|rsnum=2075650
}}

{{PMID Auto GWAS
|PMID=20595579
|Trait=Longevity
|Title=Genetic Signatures of Exceptional Longevity in Humans.
|RiskAllele=A
|Pval=8E-12
|OR=2.0800
|ORtxt=[NR]
}}

{{PMID Auto GWAS
|PMID=20061627
|Trait=Alzheimer's disease
|Title=Genome-wide scan of copy number variation in late-onset Alzheimer's disease.
|RiskAllele=
|Pval=3E-11
|OR=None
|ORtxt=None
|OA=1
}}

{{PMID Auto GWAS
|PMID=21943158
|Trait=None
|Title=Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits.
|RiskAllele=G
|Pval=2E-14
|OR=0.1530
|ORtxt=[0.11-0.19] mmol/l increase
|OA=1
}}

{{PMID Auto
|PMID=22445811
|Title=Genetic variants influencing human aging from late-onset Alzheimer's disease (LOAD) genome-wide association studies (GWAS)
}}

{{PMID Auto
|PMID=17434289
|Title=Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer's disease: patterns of linkage disequilibrium and disease/marker association.
|OA=1
}}

{{PMID Auto
|PMID=18262040
|Title=LDL-cholesterol concentrations: a genome-wide association study.
|OA=1
}}

{{PMID Auto
|PMID=18439548
|Title=Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study.
|OA=1
}}

{{PMID Auto
|PMID=19060910
|Title=Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.
|OA=1
}}

{{PMID Auto
|PMID=19118814
|Title=Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease.
|OA=1
}}

{{PMID Auto
|PMID=19197348
|Title=Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.
|OA=1
}}

{{PMID Auto
|PMID=19299407
|Title=Replication of genetic associations with plasma lipoprotein traits in a multiethnic sample.
|OA=1
}}

{{PMID Auto
|PMID=19951432
|Title=Analysis of recently identified dyslipidemia alleles reveals two loci that contribute to risk for carotid artery disease.
|OA=1
}}

{{PMID Auto
|PMID=20451875
|Title=Alzheimer's Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans.
|OA=1
}}

{{PMID Auto
|PMID=21379329
|Title=Genome-wide association of familial late-onset Alzheimer's disease replicates BIN1 and CLU and nominates CUGBP2 in interaction with APOE.
|OA=1
}}

{{PMID Auto
|PMID=21418511
|Title=Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited.
|OA=1
}}

{{PMID Auto
|PMID=21459483
|Title=Using CSF biomarkers to replicate genetic associations in Alzheimer's disease.
|OA=1
}}

{{PMID Auto
|PMID=21647738
|Title=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.
|OA=1
}}

{{PMID Auto GWAS
|PMID=22694956
|Trait=None
|Title=Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3.
|RiskAllele=A
|Pval=8E-8
|OR=1.3700
|ORtxt=None
|OA=1
}}

{{GET Evidence
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs2075650
|overall_frequency_n=1420
|overall_frequency_d=10758
|overall_frequency=0.131995
|n_genomes=12
|n_genomes_annotated=0
|n_haplomes=13
|n_articles=1
|n_articles_annotated=0
|in_gwas=Y
|in_pharmgkb=Y
|autoscore=2
|webscore=N
}}

{{PMID Auto GWAS
  |PMID=23207651
  |Trait=Cognitive decline
  |Title=A genome-wide association study implicates the APOE locus in nonpathological cognitive ageing.
  |RiskAllele=G
  |Pval=2E-8
  |OR=.20
  |ORtxt=[0.12-0.28] unit decrease
  }}

{{PMID Auto GWAS
  |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.
  |RiskAllele=A
  |Pval=1E-6
  |OR=1.23
  |ORtxt=[1.13-1.34]
  |OA=1
}}

{{PMID Auto
|PMID=23001569
|Title=Gene-centric meta-analyses of 108 912 individuals confirm known body mass index loci and reveal three novel signals
|OA=1
}}

{{PMID Auto
|PMID=23288655
|Title=Association of TOMM40 polymorphisms with late-onset Alzheimer's disease in a Northern Han Chinese population
}}

{{PMID Auto GWAS
  |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?
  |RiskAllele=G
  |Pval=2E-21
  |OR=.12
  |ORtxt=[NR] unit increase
  |OA=1
}}

{{PMID Auto
|PMID=24549102
|Title=TOMM40 rs2075650 May Represent a New Candidate Gene for Vulnerability to Major Depressive Disorder
}}

{{PMID Auto
|PMID=22430674
|Title=Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease.
|OA=1
}}

{{PMID Auto
|PMID=22710912
|Title=TOMM40, APOE, and APOC1 in primary progressive aphasia and frontotemporal dementia.
}}

{{PMID Auto
|PMID=23040522
|Title=Apolipoprotein E and familial longevity.
|OA=1
}}

{{PMID Auto
|PMID=23100282
|Title=Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.
|OA=1
}}

{{PMID Auto
|PMID=23193196
|Title=Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimer's disease, multiple sclerosis and endometriosis.
|OA=1
}}

{{PMID Auto
|PMID=23546992
|Title=TOMM40 polymorphisms in Italian Alzheimer's disease and frontotemporal dementia patients.
}}

{{PMID Auto
|PMID=24788522
|Title=Genetic variation at the CELF1 (CUGBP, elav-like family member 1 gene) locus is genome-wide associated with Alzheimer's disease and obesity
}}

{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}