TOMM40 rs2075650: Understanding the Genetic Link to Alzheimer's
The rs2075650 variant is a single nucleotide polymorphism located within the TOMM40 gene on chromosome 19. It is frequently studied alongside the nearby APOE gene due to its statistical associations with late-onset Alzheimer's disease and variations in cognitive performance.
What each genotype means
Baseline risk profile
This genotype is considered the baseline or reference state for this variant. Some research suggests that individuals with this genotype may have a slightly lower risk for Alzheimer's disease and a potential association with greater longevity compared to those carrying the G allele.
This is the most common genotype observed across all major human populations.
Increased risk association
Carrying one copy of the G allele has been associated in some studies with a higher risk of Alzheimer's disease and differences in brain imaging markers related to cognitive aging. However, because this variant is located near the APOE gene, it is often difficult to determine if these effects are independent or due to linkage with other nearby genetic factors.
This genotype is common, though its exact frequency varies significantly depending on ancestral background.
Elevated risk association
Individuals with this genotype carry two copies of the G allele, which has been statistically associated with an increased risk of Alzheimer's disease and changes in brain structure in some research cohorts. It is important to note that because this variant is in close proximity to the APOE gene, these associations may be influenced by linkage disequilibrium with other nearby variants rather than acting independently.
This genotype is less common than the AA or AG genotypes in most populations.
What is rs2075650?
The rs2075650 variant is a specific change in the DNA sequence, known as a single nucleotide polymorphism (SNP), located on chromosome 19. It sits within the TOMM40 gene, which is positioned in a region of the genome that is highly complex and biologically significant. This region also contains the APOE gene, a well-known factor in Alzheimer's disease research. Because these genes are located very close to one another, they are often inherited together in blocks, a phenomenon known as linkage disequilibrium. This makes it challenging for researchers to determine whether observed health associations are driven by the TOMM40 variant itself, the nearby APOE variants, or a combination of both. Scientists use large-scale genome-wide association studies (GWAS) to track how often this specific SNP appears in individuals with certain traits compared to those without them.
The Role of the TOMM40 Gene
The TOMM40 gene encodes a protein called the translocase of outer mitochondrial membrane 40. This protein is a critical component of a channel that allows proteins to enter the mitochondria, the powerhouses of the cell. Mitochondria are essential for energy production, and their proper function is vital for the health of neurons in the brain. When the TOMM40 protein is not functioning correctly, it may lead to mitochondrial dysfunction, which has been implicated in various neurodegenerative processes. Research into this gene aims to understand how its expression or structural variations might contribute to cellular stress or inflammation. While the gene's primary function is well-documented, the specific impact of the rs2075650 variant on protein function remains a subject of ongoing investigation, as researchers work to distinguish its effects from the neighboring APOE locus.
Research and Associations
The rs2075650 variant has been the subject of numerous studies investigating its link to late-onset Alzheimer's disease and cognitive decline. Some research has suggested that individuals carrying the G allele may experience an earlier onset of Alzheimer's symptoms compared to those with the A allele. Additionally, some studies have identified associations between this SNP and performance on memory-related tasks, such as delayed recall. However, the evidence is nuanced; many researchers emphasize that these associations are often statistically driven by the strong influence of the nearby APOE ε4 allele. Furthermore, findings can vary significantly between different ancestral populations. For instance, some studies have failed to replicate associations found in European cohorts when looking at other populations, such as Han Chinese cohorts. Because of these complexities, the evidence for rs2075650 as an independent risk factor is considered moderate and continues to be refined by the scientific community.
Population Frequency
The rs2075650 variant is considered a common SNP in many populations. Its frequency can vary depending on ancestral background, which is a standard observation in human genetics. In some datasets, the minor allele frequency is high enough that a significant portion of the population carries at least one copy of the variant. It is important to note that 'common' does not imply a specific health outcome; rather, it describes the prevalence of the genetic change within the human gene pool. Because this variant is located in a region with high linkage disequilibrium, its frequency is often analyzed in the context of the broader genetic architecture of chromosome 19.
Interpreting Genetic Information
Understanding your genetic profile regarding rs2075650 can be an educational experience, but it is not a diagnostic tool. Genetic associations are statistical probabilities observed across large groups of people, not individual predictions of health. Because Alzheimer's disease is a complex condition influenced by a combination of genetics, lifestyle, and environmental factors, a single SNP cannot determine an individual's risk. If you have questions about your cognitive health or family history, it is essential to consult with a healthcare professional or a genetic counselor. They can provide context based on your personal medical history and help you understand what current research means for you. Never use genetic data to make medical decisions or change your lifestyle without professional guidance, as these results are intended for informational purposes only.
How common is this variant?
The rs2075650 variant is common across many global populations, though specific allele frequencies vary by ancestry.
Frequently asked questions
Does having the G allele mean I will get Alzheimer's?
No. Genetic associations are statistical, not deterministic. Many people with the G allele never develop Alzheimer's, and many people without it do.
Is rs2075650 the same as APOE?
No, they are different genes. However, they are located very close to each other on chromosome 19, which means they are often inherited together.
Can I change my risk based on this SNP?
You cannot change your DNA. However, maintaining a healthy lifestyle, including regular exercise and a balanced diet, is generally recommended for brain health regardless of your genetic profile.
Should I get tested for this variant?
Clinical testing for this specific SNP is not standard practice for diagnosing Alzheimer's disease. Consult a doctor if you have concerns about memory loss or cognitive changes.
Sources & further reading
Educational information only, last refreshed 10/8/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs2075650?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in TOMM40
This variant is in linkage disequilibrium with APOE and is associated with the age of onset for late-onset Alzheimer's disease.
Variant in TOMM40 associated with mitochondrial function and aging markers.
Functional intronic variant in TOMM40 associated with human longevity, mitochondrial protein import integrity, and delay in cognitive decline.