RGD Reference Report - Intermediate phenotypes identify divergent pathways to Alzheimer's disease. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Intermediate phenotypes identify divergent pathways to Alzheimer's disease.

Authors: Shulman, JM  Chibnik, LB  Aubin, C  Schneider, JA  Bennett, DA  De Jager, PL 
Citation: Shulman JM, etal., PLoS One. 2010 Jun 21;5(6):e11244. doi: 10.1371/journal.pone.0011244.
RGD ID: 10427727
Pubmed: PMID:20574532   (View Abstract at PubMed)
PMCID: PMC2888589   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0011244   (Journal Full-text)

BACKGROUND: Recent genetic studies have identified a growing number of loci with suggestive evidence of association with susceptibility to Alzheimer's disease (AD). However, little is known of the role of these candidate genes in influencing intermediate phenotypes associated with a diagnosis of AD, including cognitive decline or AD neuropathologic burden. METHODS/PRINCIPAL FINDINGS: Thirty-two single nucleotide polymorphisms (SNPs) previously implicated in AD susceptibility were genotyped in 414 subjects with both annual clinical evaluation and completed brain autopsies from the Religious Orders Study and the Rush Memory and Aging Project. Regression analyses evaluated the relation of SNP genotypes to continuous measures of AD neuropathology and cognitive function proximate to death. A SNP in the zinc finger protein 224 gene (ZNF224, rs3746319) was associated with both global AD neuropathology (p = 0.009) and global cognition (p = 0.002); whereas, a SNP at the phosphoenolpyruvate carboxykinase locus (PCK1, rs8192708) was selectively associated with global cognition (p = 3.57 x 10(-4)). The association of ZNF224 with cognitive impairment was mediated by neurofibrillary tangles, whereas PCK1 largely influenced cognition independent of AD pathology, as well as Lewy bodies and infarcts. CONCLUSIONS/SIGNIFICANCE: The findings support the association of several loci with AD, and suggest how intermediate phenotypes can enhance analysis of susceptibility loci in this complex genetic disorder.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease susceptibilityIAGP 10427727DNA:SNP: :APOEe4(human)RGD 
Alzheimer's disease susceptibilityISOAPOE (Homo sapiens)10427727; 10427727DNA:SNP: :APOEe4(human)RGD 
Alzheimer's disease disease_progressionIAGP 10427727DNA:SNP: :rs8192708(human)RGD 
Alzheimer's disease disease_progressionISOPCK1 (Homo sapiens)10427727; 10427727DNA:SNP: :rs8192708(human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer disease susceptibilityIAGP 10427727DNA:SNP: ::rs3746319(human)RGD 
Cotton wool plaques  IAGP 10427727DNA:SNP: :APOEe4(human)RGD 
Cotton wool plaques  IAGP 10427727DNA:SNP: ::rs3745833(human)RGD 
Impaired visuospatial constructive cognition  IAGP 10427727DNA:SNP: :APOEe4(human)RGD 
Impaired visuospatial constructive cognition  IAGP 10427727DNA:SNP: ::rs3746319(human)RGD 
Neurofibrillary tangles  IAGP 10427727DNA:SNP: :APOEe4(human)RGD 
Neurofibrillary tangles  IAGP 10427727DNA:SNP: ::rs3746319(human)RGD 
Senile plaques  IAGP 10427727DNA:SNP: :APOEe4(human)RGD 
Senile plaques  IAGP 10427727 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Apoe  (apolipoprotein E)
Pck1  (phosphoenolpyruvate carboxykinase 1)

Genes (Mus musculus)
Apoe  (apolipoprotein E)
Pck1  (phosphoenolpyruvate carboxykinase 1, cytosolic)

Genes (Homo sapiens)
APOE  (apolipoprotein E)
GALP  (galanin like peptide)
PCK1  (phosphoenolpyruvate carboxykinase 1)
ZNF224  (zinc finger protein 224)


Additional Information