P4‐010: Genome‐wide association study of the robust aging in adult changes of thought (ACT)
Year: 2015
Type: article
Study design: Observational Study
Abstract: Several studies have evaluated the genetic basis of cognitive decline and of longevity. Few have evaluated whether common genetic variants may be important predictors of the more global construct of robust aging. We defined robust aging as follows: 1. Survival to age 85; 2. Able to walk defined by a timed walk faster than our previously published frailty threshold; 3. Not demented, defined by DSM-IV criteria; and 4. Not depressed as measured by the Centers for Epidemiological Study Depression scale (CES-D). Failure to meet any one of these represented a failure. We included data from the 1,227 men and women from the Adult Changes in Thought (ACT) study born before 1929 (thus at risk for survival to 85) who had genome-wide SNP data available. We entered known robust-aging predictors including age, physical comorbidity scores, exercise, cognitive function, CESD in a survival model. We took the residuals from that model as our phenotype for genetic analyses. Using residuals effectively eliminates the influence of these factors already known to be associated with robust aging, enabling us to focus more closely on novel genetic factors. We used PLINK to perform a genome-wide association study of the robust aging phenotype adjusting for population substructure. We identified two genes with suggestive genetic signals: PTPRT (Chr 20: rs11698118; p-value = 9.3×10) and CDCP1 (Chr 3: rs58423206; p-value = 1.2×10). PTPRT codes for receptor protein tyrosine phosphatase rho, a transmembrane protein highly expressed in the developing and adult CNS. Basic science investigations suggest that PTPRT appears to be essential for synapse formation. CDCP1encodes a transmembrane protein plays a role in the tyrosine phosphorylation-dependent regulation of cellular events that are involved in tumor invasion and metastasis.
Source: Alzheimer s & Dementia
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2464975795