What you carry at this position in your DNA and what research says about it.
Dementia Risk: 4/10 evidence, 42 publications.
You're viewing every possible genotype for this variant.
None of these is your result. Use the genotype toggle to compare them, then sign up and upload your DNA to see which one is yours.
Sample genotype (not yours): C/C
Lower Risk of Dementia and Higher Progranulin Levels
Having two copies of the C allele is associated with optimal progranulin protein production. This genotype is linked to a lower risk of developing frontotemporal dementia and Alzheimer's disease compared to T allele carriers.
What this genotype means: Normal progranulin protein production; Lower risk of frontotemporal dementia; Slightly higher risk of type 2 diabetes.
Sample genotype (not yours): C/T
Moderately Increased Risk of Dementia
Carrying one copy of the T allele is associated with a moderate reduction in progranulin protein levels. This reduction leads to a slightly elevated risk of developing frontotemporal dementia and Alzheimer's disease.
What this genotype means: Intermediate progranulin protein levels; Moderately increased risk of frontotemporal dementia; Slightly increased risk of Alzheimer's disease.
Sample genotype (not yours): T/T
Increased Risk of Dementia and Lower Progranulin Levels
Carrying two copies of the T allele significantly reduces progranulin protein production. This genetic profile is associated with an increased risk of frontotemporal dementia and Alzheimer's disease.
What this genotype means: Lowest progranulin protein levels; Increased risk of frontotemporal dementia; Increased risk of Alzheimer's disease.
Gene function and biological role
Gene Function: The GRN gene provides instructions for making progranulin, a versatile protein active in many cell types throughout the body [1]. In the brain, progranulin is crucial for regulating inflammation, supporting cell survival, and maintaining lysosomal health [1] [2]. Normal levels of this protein help protect neurons from premature aging and degeneration [2]. When progranulin levels are insufficient, neurons become vulnerable to damage, which can lead to cognitive decline and neurodegenerative conditions [2].
Variant Impact: The rs5848 variant is a single-nucleotide change located in the 3-prime untranslated region of the GRN gene [2]. This specific region acts as a binding site for microRNA-659, a molecule that regulates how much progranulin protein is translated and produced [2]. The T allele increases the binding efficiency of microRNA-659, which leads to stronger suppression of progranulin translation [2] [3]. As a result, individuals carrying the T allele produce significantly less progranulin in both their blood and brain tissue [3]. This reduction in progranulin mimics some of the biological effects seen in genetic forms of dementia [2].
Key Insight: The T allele acts like a dimmer switch, allowing a regulatory molecule called microRNA-659 to bind more tightly and turn down the production of protective progranulin protein by up to thirty percent.
Location: GRN. Chromosome 17 · 17q21.31 · 44.4 Mb
Estimated prevalence by population
Global 38.2%; European 49.7%; African 10.8%; East Asian 41.9%; South Asian 45.0%; Americas 55.1%; Ashkenazi 36.9%; Finnish 40.6%; Middle Eastern 43.2%; Amish 54.1%.
Estimated CC genotype frequency.
Global 42.6%; European 41.6%; African 44.1%; East Asian 45.7%; South Asian 44.1%; Americas 38.2%; Ashkenazi 47.7%; Finnish 46.2%; Middle Eastern 45.0%; Amish 38.9%.
Estimated CT genotype frequency.
Global 19.2%; European 8.7%; African 45.2%; East Asian 12.4%; South Asian 10.8%; Americas 6.6%; Ashkenazi 15.4%; Finnish 13.2%; Middle Eastern 11.7%; Amish 7.0%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Neurology & Mental Health
Neurodegenerative Diseases
Frontotemporal Dementia. Evidence: 4/10. Source: PMID 18723524. Lower Risk.
Alzheimer's Disease. Evidence: 8/10. Source: PMID 35379992. Lower Risk.
Progranulin Levels. Evidence: 6/10. Source: PMID 29186428. Highest Levels.
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 4/10. Source: PMID 34737425. ~1.2x Higher Risk.
Showing effects for C/T genotype
Frontotemporal Dementia. Evidence: 4/10. Source: PMID 18723524. Increased Risk.
Alzheimer's Disease. Evidence: 8/10. Source: PMID 35379992. Slightly Higher Risk.
Progranulin Levels. Evidence: 6/10. Source: PMID 29186428. Intermediate Levels.
Type 2 Diabetes. Evidence: 4/10. Source: PMID 34737425. Intermediate Risk.
Showing effects for T/T genotype
Frontotemporal Dementia. Evidence: 4/10. Source: PMID 18723524. ~1.9x Higher Risk.
Progranulin Levels. Evidence: 6/10. Source: PMID 29186428. Lowest Levels.
Type 2 Diabetes. Evidence: 4/10. Source: PMID 34737425. Lower Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Maintaining adequate levels of progranulin is essential for protecting brain cells from age-related damage and inflammation [1]. This genotype represents the baseline genetic state where microRNA-659 binds less efficiently to the GRN gene, allowing for normal translation of the progranulin protein [1]. Studies show that individuals with this genotype have the highest circulating levels of progranulin in both blood and cerebrospinal fluid [2]. Consequently, this genetic profile is associated with a significantly lower risk of frontotemporal dementia and related neurodegenerative conditions [1]. However, some research suggests a slightly higher susceptibility to type 2 diabetes, indicating a complex metabolic trade-off [3]. Overall, this genotype is considered highly favorable for long-term brain health and cognitive preservation.
Normal progranulin protein production; Lower risk of frontotemporal dementia; Slightly higher risk of type 2 diabetes.
Sample genotype: CT (Heterozygous)
A single copy of the T allele alters the binding site for microRNA-659, allowing it to suppress the translation of the GRN gene more effectively [1]. This increased binding results in intermediate levels of progranulin protein in both blood and brain tissues [2]. Because progranulin is vital for neuronal survival and managing brain inflammation, this reduction can gradually increase vulnerability to neurodegeneration [1]. Clinical studies and meta-analyses have linked this genotype to a moderately higher risk of frontotemporal dementia and Alzheimer's disease compared to the C/C genotype [1] [3]. While the risk is elevated, it is not a direct cause of disease, and many carriers remain healthy throughout their lives. It serves as one of several genetic factors that influence overall cognitive resilience during aging.
Intermediate progranulin protein levels; Moderately increased risk of frontotemporal dementia; Slightly increased risk of Alzheimer's disease.
Sample genotype: TT (Homozygous)
Having two copies of the T allele creates a highly efficient binding site for microRNA-659, which strongly suppresses the translation of progranulin [1]. This leads to the lowest levels of circulating progranulin protein among all three genotypes, with reductions of up to thirty percent [2]. Because progranulin is a key neuroprotective factor, this deficit mimics some of the cellular pathways seen in familial forms of dementia [1]. Research indicates that this genotype is associated with an approximately three-fold increase in the risk of frontotemporal lobar degeneration [1]. It is also linked to a higher risk of Alzheimer's disease, particularly in older populations [3]. Conversely, some studies suggest this genotype may offer a lower risk of type 2 diabetes, highlighting a metabolic trade-off [4].
Lowest progranulin protein levels; Increased risk of frontotemporal dementia; Increased risk of Alzheimer's disease; Lower risk of type 2 diabetes.
Variants with shared genetic architecture
rs10792832 · PICALM Gene · Chr 11 · Alzheimer Disease Risk
rs6859 · NECTIN2 Gene · Chr 19 · Alzheimer's Disease Risk
rs1476679 · ZCWPW1 Gene · Chr 7 · Alzheimer's Disease Risk
rs5848 polymorphism and serum progranulin level.
Progranulin polymorphism rs5848 is associated with increased risk of Alzheimer's disease.
rs5848 variant of progranulin gene is a risk of Alzheimer's disease in the Taiwanese population.
Content updated August 2026.
ReadYourDNA provides educational interpretation of DNA data you already have. It is not diagnostic, not a substitute for professional medical advice, diagnosis, or treatment, and is not intended to diagnose, treat, cure, or prevent any disease. Talk to a clinician before acting on any result.
Raw DNA Data Reports for 23andMe & AncestryDNA · About ReadYourDNA · FAQ · Methodology & Science · Pricing · Support and complaints · Legal & Contact · Health Traits · Pharmacogenomics · Carrier Status · Variant Explorer · The Human Karyotype · Privacy Policy · Terms of Service · Accessibility · Consumer Health Data Privacy · Your Privacy Choices · Editorial Standards · Your Data, Checkable · Sample Report · ReadYourDNA and Promethease compared · What is inside a 23andMe raw data file · What is inside an AncestryDNA raw data file · What a chatbot can and cannot do with your raw DNA file · Where a raw DNA file can still be uploaded in 2026
Written, maintained and operated by Martin Pechhacker, sole proprietor, Vienna, Austria. Trade register GISA 40064420. support@readyourdna.com