P1‐252: Evaluation of Cognitive Endophenotypes for Association with CLU, CR1 and PICALM LOAD Risk Genes
Year: 2011
Type: article
Study design: Observational Study
Abstract: Cognitive endophenotypes can be useful for identifying novel genetic risk loci for late onset Alzheimer's disease (LOAD) and for evaluating their influence on disease pathways. CLU, CR1 and PICALM are novel AD loci identified in large genome-wide association studies (GWAS). We evaluated three SNPs at these loci for association with memory endophenotypes in elderly adults. Subjects included non-demented controls (n∼1100-2400) and AD patients (n∼300), recruited in studies of aging at Mayo Clinic. Phenotypes were identified from the Auditory Verbal Learning Test: Learning-over-trials (AVLOT), long-delay recall (AVDR), and percent retention (AVPR); Logical Memory: Immediate recall (LMIR), long-delay recall (LMDR), and percent retention (LMPR); Visual Reproduction: Immediate recall (VRIR), long-delay recall (VRDR), and percent retention (VRPR). Phenotypes were selected from the last available examinations. Subjects were genotyped for CLU rs11136000, PICALM rs3851179 and CR1 rs6656401 SNPs. Linear regression analyses were done in PLINK with age, sex, APOE e4 allele, and education as covariates in controls-only analyses, and clinical diagnosis as an additional covariate in the combined analyses of cases and controls. In the case+controls analyses, CLU rs11136000 was significantly associated with better scores for multiple phenotypes from Logical Memory, namely LMDR (b = 0.94, p = 0.0042), LMPR (b = 2.74, p = 0.01) and LMIR (b = 0.69, p = 0.03). Similar results for CLU were obtained in controls-only analyses, where LMDR (b = 0.82, p = 0.0067) and LMPR (b = 1.87, p = 0.015) associations were significant and that for LMIR (b = 0.49, p = 0.07) was marginal. No other significant associations were observed for the combined cases and controls, although marginal associations were noted for PICALM rs3851179 SNP in controls only for LMPR (b = −1.61, p = 0.046) and LMDR (b = −0.54, p = 0.09). Our results show that the CLU rs11136000 SNP, which is associated with reduced risk of AD, is also associated with improved memory scores in non-demented elderly subjects. Thus, in our dataset, the CLU locus had an influence on cognition that was detectable prior to clinical diagnosis of dementia. Though replication is needed, these results provide further support for CLU in AD and suggest a role for cognitive endophenotypes in genetic studies of dementia.
Source: Alzheimer s & Dementia
Institutions: Mayo Clinic in Florida, Mayo Clinic
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2134636608