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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.
Pubmed: (View Article at PubMed) PMID:16013913

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.

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CRRD Object Information
CRRD ID: 5685661
Created: 2012-01-16
Species: All species
Last Modified: 2012-01-16
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.