{{Rsnum
|rsid=5848
|Gene=GRN
|Chromosome=17
|position=44352876
|Orientation=minus
|GMAF=0.3861
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=GRN
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 4.4 | 38.9 | 56.6
| HCB | 13.1 | 43.8 | 43.1
| JPT | 5.4 | 42.9 | 51.8
| YRI | 59.6 | 37.0 | 3.4
| ASW | 35.1 | 50.9 | 14.0
| CHB | 13.1 | 43.8 | 43.1
| CHD | 14.7 | 46.8 | 38.5
| GIH | 9.1 | 36.4 | 54.5
| LWK | 36.1 | 51.9 | 12.0
| MEX | 6.9 | 32.8 | 60.3
| MKK | 19.5 | 46.1 | 34.4
| TSI | 5.9 | 46.5 | 47.5
| HapMapRevision=28
}}
[[rs5848]](T;T) found a 3.2-fold increased risk vs C-allele carriers (95% CI: 1.50-6.73, p=0.003) for ubiquitin- and TAR DNA-binding protein 43 ([[TDP-43]])-positive [[frontotemporal dementia]] (FTLD-U also knows as FTLD-TDP43), a progressive neurodegenerative disease affecting approximately 10% of early-onset [[dementia]] patients. Detailed haplotype analysis was conducted, indicating [[rs5848]] as most likely causal variant. FTLD-TDP43 is divided into four subtypes, some sources suggest association with type 3 only {{PMID|16862115}}. Association between [[rs5848]](T;T) and [[frontotemporal dementia]] is now generally assumed in literature, despite some studies failing to reproduce it.

First meta-analysis of [[rs5848]] association with [[Alzheimer's disease]] combining previous five studies for a total of 2502 [[Alzheimer's disease]] cases and 2162 controls found association in homozygous model (TT vs. CC: OR, 1.36; 95% CI, 1.11-1.66; P=0.003) as well as recessive model. This association existed also in the Caucasian-only subset of 2227 cases and 1902 controls. Although the ''p''-value is above usually applied guidelines, the researchers concluded the data indicates association exists {{PMID|24680777}}.  According to "First symptoms--frontotemporal dementia versus Alzheimer's disease" {{PMID|10940680}} as well as other sources frontotemporal [[dementia]] is often misdiagnosed as [[Alzheimer's disease]] so it is possible some studies have misdiagnosed cases. FTLD is characterized by behavioral and/or language dysfunction, but usually without the amnesic syndrome involved in [[Alzheimer's disease]] at early stage.

In contrast "Reduced serum progranulin level might be associated with Parkinson's disease risk" {{PMID|23398167}} found that only [[Parkinson's disease]] was associated with reduces progranulin levels, but found no association between progranulin levels, [[rs5848]] or [[Alzheimer's disease]]. "Association between GRN rs5848 polymorphism and Parkinson's disease in Taiwanese population" found association between [[rs5848]] and [[Parkinson's disease]], but only for female Taiwanese (OR = 1.43, 95% CI: 1.11-1.87, P = 0.007 for single T allele among females). Most studies have found association with neurodegenerative disorders only for recessive or homozygous model, but this is one study where odds ratio follows number of alleles (OR=2.16, 95% CI: 1.24-3.78, P = 0.006 for two alleles among females).

A functional effect is suggested in many studies such as "GRN variant rs5848 reduces plasma and brain levels of granulin in Alzheimer's disease patients" {{PMID|22890097}} and "Rs5848 variant influences GRN mRNA levels in brain and peripheral mononuclear cells in patients with Alzheimer's disease" {{PMID|19625741|OA=1
}}. In addition "rs5848 polymorphism and serum progranulin level" {{PMID|21047645|OA=1
}} showed that progranulin level is affected by number of (T) alleles equally both in 100 patients with different forms of dementia and 36 controls: TT (164 ng/mL, 95% C.I. 138-189), CT (191 ng/mL, 95% C.I. 177-206) and CC (222 ng/mL, 95% C.I. 205-238) serum progranulin with p < 0.005. Progranulin is a growth-factor involved in regulating tumorigenesis, wound repair, development, and inflammation among other things. [[Rs5848]] is located in the 3'-untranslated region (UTR) RNA tail of GRN in a binding-site for miR-659 which inhibits [[GRN]] translation. University of California, San Francisco is currently conducting clinical trial "[http://clinicaltrials.gov/ct2/show/record/NCT01835665|Dose Finding Study of Nimodipine for the Treatment of Progranulin Insufficiency From GRN Gene Mutations]".

{{PMID Auto GWAS
|PMID=24680777
|Trait=Alzheimer's disease
|Title=Progranulin polymorphism rs5848 is associated with increased risk of Alzheimer's disease.
|RiskAllele=TT
|Pval=6E-3
|OR=1.31
|ORtxt=[1.08-1.58] recessive model
}}
{{PMID|18723524|OA=1
}} Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia.
{{PMID Auto
|PMID=19446372
|Title=No association of PGRN 3'UTR rs5848 in frontotemporal lobar degeneration
}}
{{PMID Auto
|PMID=19473366
|Title=GRN 3'UTR+78 C&gt;T is not associated with risk for Parkinson's disease
}}

{{PMID Auto
|PMID=19847305
|Title=Variation at GRN 3'-UTR rs5848 Is Not Associated with a Risk of Frontotemporal Lobar Degeneration in Dutch Population
|OA=1
}}
{{PMID Auto
|PMID=19876635
|Title=Sporadic corticobasal syndrome due to FTLD-TDP
|OA=1
}}

{{PMID Auto
|PMID=20197700
|Title=Common Variant in GRN Is a Genetic Risk Factor for Hippocampal Sclerosis in the Elderly
|OA=1
}}

{{PMID Auto
|PMID=20061636
|Title=GRN variability contributes to sporadic frontotemporal lobar degeneration
}}
{{PMID Auto
|PMID=20711061
|Title=Prion Protein Codon 129 Polymorphism Modifies Age at Onset of Frontotemporal Dementia With the C.709-1G&gt;A Progranulin Mutation
|OA=1
}}

{{omim
|id=138945
|desc=GRANULIN PRECURSOR; GRN
|rsnum=5848
}}
{{PMID Auto
|PMID=21047645
|Title=rs5848 polymorphism and serum progranulin level
|OA=1
}}
{{PMID Auto
|PMID=21212639
|Title=rs5848 Variant of Progranulin Gene Is a Risk of Alzheimer's Disease in the Taiwanese Population
}}

{{omim
|id=607485
|rsnum=5848
}}

{{PMID Auto
|PMID=16251468
|Title=Survey of allelic expression using EST mining.
|OA=1
}}

{{PMID Auto
|PMID=18192287
|Title=Frequency and clinical characteristics of progranulin mutation carriers in the Manchester frontotemporal lobar degeneration cohort: comparison with patients with MAPT and no known mutations.
}}

{{PMID Auto
|PMID=19016491
|Title=An association study between granulin gene polymorphisms and Alzheimer's disease in Finnish population.
}}

{{PMID Auto
|PMID=19625741
|Title=Rs5848 variant influences GRN mRNA levels in brain and peripheral mononuclear cells in patients with Alzheimer's disease.
|OA=1
}}

{{PMID Auto
|PMID=19640594
|Title=Recent insights into the molecular genetics of dementia.
|OA=1
}}

{{PMID Auto
|PMID=21346515
|Title=Hippocampal sclerosis in the elderly: genetic and pathologic findings, some mimicking Alzheimer disease clinically.
|OA=1
}}

{{PMID Auto
|PMID=23342160
|Title=Association between GRN rs5848 Polymorphism and Parkinson's Disease in Taiwanese Population
|OA=1
}}

{{PMID Auto
|PMID=24499389
|Title=Progranulin gene variability influences the risk for bipolar I disorder, but not bipolar II disorder
}}

{{PMID Auto
|PMID=24581833
|Title=Further evidence for plasma progranulin as a biomarker in bipolar disorder
}}

{{PMID Auto
|PMID=22890097
|Title=GRN variant rs5848 reduces plasma and brain levels of granulin in Alzheimer's disease patients.
}}

{{PMID Auto
|PMID=23398167
|Title=Reduced serum progranulin level might be associated with Parkinson's disease risk.
}}

{{PMID Auto
|PMID=24770881
|Title=ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology
}}

{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}