Fine Mapping of Genetic Variants in BIN1, CLU, CR1 and PICALM for Association with Cerebrospinal Fluid Biomarkers for Alzheimer's Disease
Year: 2011
Type: article
Study design: Observational Study
Abstract: Recent genome-wide association studies of Alzheimer's disease (AD) have identified variants in BIN1, CLU, CR1 and PICALM that show replicable association with risk for disease. We have thoroughly sampled common variation in these genes, genotyping 355 variants in over 600 individuals for whom measurements of two AD biomarkers, cerebrospinal fluid (CSF) 42 amino acid amyloid beta fragments (Aβ(42)) and tau phosphorylated at threonine 181 (ptau(181)), have been obtained. Association analyses were performed to determine whether variants in BIN1, CLU, CR1 or PICALM are associated with changes in the CSF levels of these biomarkers. Despite adequate power to detect effects as small as a 1.05 fold difference, we have failed to detect evidence for association between SNPs in these genes and CSF Aβ(42) or ptau(181) levels in our sample. Our results suggest that these variants do not affect risk via a mechanism that results in a strong additive effect on CSF levels of Aβ(42) or ptau(181).
Source: PLoS ONE
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: Foundation for the National Institutes of Health, U.S. Department of Veterans Affairs, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, Alzheimer's Disease Neuroimaging Initiative, Foundation for Barnes-Jewish Hospital, Northern California Institute for Research and Education, Elan, Eisai, National Institutes of Health, U.S. Food and Drug Administration, University of California, Los Angeles, University of California, San Diego, National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering
Awards: G104586243, G1153207773, G120329898, G144593012, G1961535950, G2152643862, G2307429633, G239217577, G2835601961, G29951154, G3131374986, G3146424788, G3553156159, G3705772492, G3710456697, G43180419, G4633544157, G5207404921, G5209990037, G5389965057, G561739401, G5678256514, Alzheimer's Disease Neuroimaging Initiative, G6011050370, G6259281481, G6650652509, G6899163935, Alzheimer's Disease Research Center, G710411779, Healthy Aging and Senile Dementia, Biomarkers in Aging, MCI and Alzheimer's Disease, G7414321945, Alzheimer's Disease Research Center, G7799614282, G781725486, Alzheimer's Disease Cooperative Study, GENOMIC SEARCH FOR SUSCEPTIBILITY TO ALZHEIMER DISEASE, G9000039018, G9000122335, G9000190416, Antecedent Biomarkers for Alzheimer Disease: The Adult Children Study, G920654007
OpenAlex ID: W2002989619