10 research outputs found
High polygenic risk score for exceptional longevity is associated with a healthy metabolic profile
Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individualâs polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELPRS have a low prevalence of MetS. Participants were from five cohorts of middle-aged to older adults. The primary analyses were performed in the UK Biobank (UKBB) (nâ=â407,800, 40â69 years). Replication analyses were undertaken using three Australian studies: Hunter Community Study (nâ=â2122, 55â85 years), Older Australian Twins Study (nâ=â539, 65â90 years) and Sydney Memory and Ageing Study (nâ=â925, 70â90 years), as well as the Swedish Gothenburg H70 Birth Cohort Studies (nâ=â2273, 70â93 years). MetS was defined using established criteria. Regressions and meta-analyses were performed with the ELPRS and MetS and its components. Generally, MetS prevalence (22â30%) was higher in the older cohorts. In the UKBB, high EL polygenic risk was associated with lower MetS prevalence (ORâ=â0.94, pâ=â1.84âĂâ10â42) and its components (pâ<â2.30âĂâ10â8). Meta-analyses of the replication cohorts showed nominal associations with MetS (pâ=â0.028) and 3 MetS components (pâ<â0.05). This work suggests individuals with a high polygenic risk for EL have a healthy metabolic profile promoting longevity
High polygenic risk score for exceptional longevity is associated with a healthy metabolic profile
Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individual's polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELPRS have a low prevalence of MetS. Participants were from five cohorts of middle-aged to older adults. The primary analyses were performed in the UK Biobank (UKBB) (nâ=â407,800, 40-69 years). Replication analyses were undertaken using three Australian studies: Hunter Community Study (nâ=â2122, 55-85 years), Older Australian Twins Study (nâ=â539, 65-90 years) and Sydney Memory and Ageing Study (nâ=â925, 70-90 years), as well as the Swedish Gothenburg H70 Birth Cohort Studies (nâ=â2273, 70-93 years). MetS was defined using established criteria. Regressions and meta-analyses were performed with the ELPRS and MetS and its components. Generally, MetS prevalence (22-30%) was higher in the older cohorts. In the UKBB, high EL polygenic risk was associated with lower MetS prevalence (ORâ=â0.94, pâ=â1.84âĂâ10-42) and its components (pâ<â2.30âĂâ10-8). Meta-analyses of the replication cohorts showed nominal associations with MetS (pâ=â0.028) and 3 MetS components (pâ<â0.05). This work suggests individuals with a high polygenic risk for EL have a healthy metabolic profile promoting longevity
Common variants in Alzheimerâs disease and risk stratification by polygenic risk scores
Funder: Funder: FundaciĂłn bancaria âLa Caixaâ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery nâ=â409,435 and validation size nâ=â58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE É4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease
Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.
Funder: Funder: FundaciĂłn bancaria âLa Caixaâ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery nâ=â409,435 and validation size nâ=â58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE É4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease
Association of CSF biomarkers with MRI brain changes in Alzheimer's disease
Abstract The relation between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and magnetic resonance imaging (MRI) measures is poorly understood in cognitively healthy individuals from the general population. Participantsâ (n = 226) mean age was 70.9 years (SD = 0.4). CSF concentrations of amyloid beta (AÎČ)1â42, total tau (tâtau), phosphorylated tau (pâtau), neurogranin, and neurofilament light, and volumes of hippocampus, amygdala, total basal forebrain (TBF), and cortical thickness were measured. Linear associations between CSF biomarkers and MRI measures were investigated. In AÎČ1â42 positives, higher tâtau and pâtau were associated with smaller hippocampus (P = 0.001 and P = 0.003) and amygdala (P = 0.005 and P = 0.01). In AÎČ1â42 negatives, higher tâtau, pâtau, and neurogranin were associated with larger TBF volume (P = 0.001, P = 0.001, and P = 0.01). No associations were observed between the CSF biomarkers and an AD signature score of cortical thickness. ADâspecific biomarkers in cognitively healthy 70âyearâolds may be related to TBF, hippocampus, and amygdala. Lack of association with cortical thickness might be due to early stage of disease
Common variants in Alzheimerâs disease and risk stratification by polygenic risk scores
Genetic discoveries of Alzheimerâs disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimerâs disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimerâs disease patients in APOE É4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimerâs disease
Recommended from our members
Nat Commun
Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE É4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease