RGD Reference Report - A cluster of cholesterol-related genes confers susceptibility for Alzheimer's disease. - Rat Genome Database

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A cluster of cholesterol-related genes confers susceptibility for Alzheimer's disease.

Authors: Papassotiropoulos, A  Wollmer, MA  Tsolaki, M  Brunner, F  Molyva, D  Lutjohann, D  Nitsch, RM  Hock, C 
Citation: Papassotiropoulos A, etal., J Clin Psychiatry. 2005 Jul;66(7):940-7.
RGD ID: 5685661
Pubmed: PMID:16013913   (View Abstract at PubMed)

OBJECTIVE: Polygenic diseases are related to the complex interplay of genetic variations. We evaluated whether clusters of cholesterol- and lipid-related genetic variations are associated with Alzheimer's disease. METHOD: We analyzed 12 cholesterol-related single nucleotide polymorphisms and 48 control polymorphisms in 545 study participants (Alzheimer's disease group N = 284; control group N = 261). Diagnoses of Alzheimer's disease were made according to the NINCDS-ADRDA criteria. Multi-locus genetic association analysis was done with the set-association method. Dates of data collection were from January 2000 to December 2003. RESULTS: We identified a cluster of polymorphisms in APOE, SOAT1, APOE 5'-untranslated region, OLR1, CYP46A1, LPL, LIPA, and APOA4 conferring significant (p = .0002) susceptibility for Alzheimer's disease. This gene cluster reached a diagnostic accuracy of 74% and correlated significantly (p = .018) with the levels of the brain cholesterol catabolite 24S-hydroxycholesterol in the cerebrospinal fluid. CONCLUSION: Our results establish a novel approach for the identification of disease-related genetic clusters and demonstrate the need for multi-locus methods in the genetics of complex diseases.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease  IAGP 5685661DNA:snp and haplotype:cds:p.S147N (rs5104) (human)RGD 
Alzheimer's disease  ISOAPOA4 (Homo sapiens)5685661; 5685661DNA:snp and haplotype:cds:p.S147N (rs5104) (human)RGD 
Alzheimer's disease  IAGP 5685661DNA:SNPs: :rs268 and rs328 (human)RGD 
Alzheimer's disease  ISOLPL (Homo sapiens)5685661; 5685661DNA:SNPs: :rs268 and rs328 (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Dementia  IAGP 5685661DNA:snp and haplotype:cds:p.S147N (rs5104)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Apoa4  (apolipoprotein A4)
Lpl  (lipoprotein lipase)

Genes (Mus musculus)
Apoa4  (apolipoprotein A-IV)
Lpl  (lipoprotein lipase)

Genes (Homo sapiens)
APOA4  (apolipoprotein A4)
LPL  (lipoprotein lipase)


Additional Information