scholarly journals Validating the role of the Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI) and a genetic risk score in progression to cognitive impairment in a population-based cohort of older adults followed for 12 years

2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Shea J. Andrews ◽  
Ranmalee Eramudugolla ◽  
Jorge I. Velez ◽  
Nicolas Cherbuin ◽  
Simon Easteal ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Risk Score ◽  
Genetic Risk ◽  
Disease Risk ◽  
Genetic Risk Score ◽  
Risk Index ◽  
Population Based ◽  
National University

scholarly journals Alzheimer’s environmental and genetic risk scores are differentially associated with ‘g’ and δ

2018 ◽  
Author(s):  
Shea J. Andrews ◽  
G. Peggy McFall ◽  
Roger A. Dixon ◽  
Nicolas Cherbuin ◽  
Ranmalee Eramudugolla ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Episodic Memory ◽  
Cognitive Performance ◽  
Risk Score ◽  
Genetic Risk ◽  
Disease Risk ◽  
Genetic Risk Score ◽  
Risk Index ◽  
Dementia Risk ◽  
National University

AbstractIntroductionWe investigated the association of the Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI) and an AD genetic risk score (GRS) with cognitive performance.MethodsThe ANU-ADRI (composed of 11 risk factors for AD) and GRS (composed of 25 AD risk loci) were computed in 1,061 community-dwelling older adults. Participants were assessed on 11 cognitive tests and activities of daily living. Structural equation modelling was used to evaluate the association of the ANU-ADRI and GRS with: 1) general cognitive ability (g) 2) dementia related variance in cognitive performance (δ) and 3) verbal ability, episodic memory, executive function and processing speed.ResultsA worse ANU-ADRI score was associated with poorer performance in ‘g’, δ, and each cognitive domain. A worse GRS was associated with poorer performance in δ and episodic memory.DiscussionThe ANU-ADRI was broadly associated with worse cognitive performance, validating its further use in early dementia risk assessment.HighlightsAn environmental/lifestyle dementia risk index is broadly associated with cognitive performanceAn Alzheimer’s genetic risk score is associated with dementia severity and episodic memoryThe environmental risk index is more strongly associated with dementia severity than genetic riskResearch in ContextSystematic ReviewThe authors reviewed the literature using online databases (e.g. PubMed). Previous research has highlighted the need for dementia risk assessment tools to be evaluated on outcomes prior to dementia onset, such as cognitive performance. The relevant citations have been appropriately cited.InterpretationThe Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI) was more broadly associated with cognitive performance than Alzheimer’s genetic risk. For the ANU-ADRI, stronger effects were observed for dementia-related variance in cognitive task performance that for variance in general cognitive function. This suggests that ANU-ADRI is more specifically associated with dementia-related processes and further validates its use in early risk assessment for dementia.Future DirectionsAccordingly, future studies should seek to evaluate the association of the ANU-ADRI and genetic risk with AD biomarkers and longitudinal cognitive performance to evaluate differential trajectories in ‘g’ and δ.

scholarly journals The Role of Genetic Risk Score in Predicting the Risk of Hypertension in the Korean population: Korean Genome and Epidemiology Study

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0131603 ◽  
Author(s):  
Nam-Kyoo Lim ◽  
Ji-Young Lee ◽  
Jong-Young Lee ◽  
Hyun-Young Park ◽  
Myeong-Chan Cho
Keyword(s):  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Korean Population ◽  
Epidemiology Study

P3399Influence of TCF21 rs12190287 in the coronary artery disease risk prediction. An association study in a Portuguese population

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Sousa ◽  
M Mendonca ◽  
A Pereira ◽  
F Mendonca ◽  
J Monteiro ◽  
...  
Keyword(s):  
Risk Score ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Disease Risk ◽  
Smoking Status ◽  
Genetic Risk Score ◽  
Strong Association ◽  
Portuguese Population ◽  
The Impact ◽  
Cad Risk

Abstract TCF21 is a member of the basic-helix-loop-helix (bHLH) transcriptor factor family, being critical for embryogenesis of the heart, kidney and spleen. TCF21 also regulates epicardium-derived cells differentiation into smooth muscle and fibroblast lineages. Aim Investigate the impact of TCF21 rs12190287 in the prediction and discrimination of CAD risk, individually or into a genetic risk score (GRS) formed by a set of 13 genetic variants. Methods We performed a case-control study with 3050 subjects (1619 coronary patients with 53.3±8 years; 78.9% male and 1431 controls with 52.8±8 years; 76.6% male) from GENEMACOR study. We investigated all traditional risk factors (TRF), as well as 13 genetic variants from GWAS with unknown pathophysiological pathway so far, including TCF21 (rs12190287), ZC3HC1 (rs11556924), PSRC1/SORTI (rs599839), PHACTR1 (rs1332844), MIA3 (rs17465637), SMAD3 (rs17228212), ZNF259 (rs964184), ADAMTS7 (rs3825807), CDKN2B (rs4977574), 9p21.3 (rs1333049), KIF6 (rs20455), PCSK9 (rs2114580) and GJA4 (rs618675). A multiplicative genetic risk score with these 13 genetic variants (m13GRS), was calculated. Subsequently, two logistic regressions were performed; primarily with all the TRF and all the genes individually and the second with TRF and m13GRS. Results The first multivariate analysis shows that, besides the strong association of the TRF with CAD risk (with smoking status on the top of the list, with an OR of 3.2; p<0.0001), TCF21 rs12190287 was the most significant variant from all the studied genetic set with a CAD risk of 1.5 (95% CI: 1.1–1.9; p=0.004), followed by the well-known genetic determinant CDKN2B rs4977574 (OR=1.4; 95% CI: 1.1–1.7; p<0.002) and ZC3HC1 rs11556924 (OR=1.3; 95% CI: 1.0–1.7; p=0.034). When GRS is included to the model, all the TRF remain in the equation by the same order, and the m13GRS persisted as an independent predictor for CAD risk (OR=1.7; 95% CI: 1.4–2.0; p<0.0001). Conclusion TCF21 rs12190287 is a risk factor for CAD in the Portuguese population, either individually or incorporated in a m13GRS. TCF21 risk is independent from TRF. In the future, TCF21 can provide a new clues to identify patients at high cardiovascular risk and become a potential target for gene therapy.

scholarly journals 959Coronary artery disease risk according to genetic risk score deciles, Age and cardiovascular risk factors

2017 ◽  
Vol 38 (suppl_1) ◽  
Author(s):  
A. Pereira ◽  
M. Neto ◽  
R. Rodrigues ◽  
J. Monteiro ◽  
A.C. Sousa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Risk Score ◽  
Genetic Risk ◽  
Disease Risk ◽  
Genetic Risk Score ◽  
Artery Disease

scholarly journals Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk Estimates

Circulation ◽  
2016 ◽  
Vol 133 (12) ◽  
pp. 1181-1188 ◽  
Author(s):  
Iftikhar J. Kullo ◽  
Hayan Jouni ◽  
Erin E. Austin ◽  
Sherry-Ann Brown ◽  
Teresa M. Kruisselbrink ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Risk Score ◽  
Coronary Heart Disease Risk ◽  
Genetic Risk ◽  
Disease Risk ◽  
Genetic Risk Score ◽  
Risk Estimates ◽  
Heart Disease Risk

scholarly journals The Nordic Nutrition Recommendations and prostate cancer risk in the Cancer of the Prostate in Sweden (CAPS) study

2012 ◽  
Vol 15 (10) ◽  
pp. 1897-1908 ◽  
Author(s):  
Elisabeth Möller ◽  
Carlotta Galeone ◽  
Hans-Olov Adami ◽  
Jan Adolfsson ◽  
Therese M-L Andersson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Prostate Cancer Risk ◽  
Positive Association ◽  
Population Based ◽  
Lifestyle Factors ◽  
Cancer Of The Prostate ◽  
Nordic Nutrition Recommendations

AbstractObjectiveThe Nordic Nutrition Recommendations (NNR) aim at preventing diet-associated diseases such as cancer in the Nordic countries. We evaluated adherence to the NNR in relation to prostate cancer (PC) in Swedish men, including potential interaction with a genetic risk score and with lifestyle factors.DesignPopulation-based case–control study (Cancer of the Prostate in Sweden (CAPS), 2001–2002). Using data from a semi-quantitative FFQ, we created an NNR adherence score and estimated relative risks of PC by unconditional logistic regression. Individual score components were modelled separately and potential modifying effects were assessed on the multiplicative scale.SettingFour regions in the central and northern parts of Sweden.SubjectsIncident PC patients (n 1386) and population controls (n 940), frequency-matched on age and region.ResultsNo overall association with PC was found, possibly due to the generally high adherence to the NNR score and its narrow distribution in the study population. Among individual NNR score components, high compared with low intakes of polyunsaturated fat were associated with an increased relative risk of localized PC. No formal interaction with genetic or lifestyle factors was observed, although in stratified analysis a positive association between the NNR and PC was suggested among men with a high genetic risk score but not among men with a medium or low genetic risk score.ConclusionsOur findings do not support an association between NNR adherence and PC. The suggestive interaction with the genetic risk score deserves further investigations in other study populations.

Dopamine Receptor Genes Modulate Associative Memory in Old Age

2017 ◽  
Vol 29 (2) ◽  
pp. 245-253 ◽  
Author(s):  
Goran Papenberg ◽  
Nina Becker ◽  
Beata Ferencz ◽  
Moshe Naveh-Benjamin ◽  
Erika J. Laukka ◽  
...  
Keyword(s):  
Older Adults ◽  
Episodic Memory ◽  
Associative Memory ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Memory Task ◽  
Population Based ◽  
Item Memory ◽  
Nucleotide Polymorphisms ◽  
Genetic Score

Previous research shows that associative memory declines more than item memory in aging. Although the underlying mechanisms of this selective impairment remain poorly understood, animal and human data suggest that dopaminergic modulation may be particularly relevant for associative binding. We investigated the influence of dopamine (DA) receptor genes on item and associative memory in a population-based sample of older adults (n = 525, aged 60 years), assessed with a face–scene item associative memory task. The effects of single-nucleotide polymorphisms of DA D1 (DRD1; rs4532), D2 (DRD2/ANKK1/Taq1A; rs1800497), and D3 (DRD3/Ser9Gly; rs6280) receptor genes were examined and combined into a single genetic score. Individuals carrying more beneficial alleles, presumably associated with higher DA receptor efficacy (DRD1 C allele; DRD2 A2 allele; DRD3 T allele), performed better on associative memory than persons with less beneficial genotypes. There were no effects of these genes on item memory or other cognitive measures, such as working memory, executive functioning, fluency, and perceptual speed, indicating a selective association between DA genes and associative memory. By contrast, genetic risk for Alzheimer disease (AD) was associated with worse item and associative memory, indicating adverse effects of APOE ε4 and a genetic risk score for AD (PICALM, BIN1, CLU) on episodic memory in general. Taken together, our results suggest that DA may be particularly important for associative memory, whereas AD-related genetic variations may influence overall episodic memory in older adults without dementia.

scholarly journals Mitonuclear interactions influence Alzheimer’s disease risk

2019 ◽  
Author(s):  
Shea J Andrews ◽  
Brian Fulton-Howard ◽  
Christopher Patterson ◽  
G Peggy McFall ◽  
Alden Gross ◽  
...  
Keyword(s):  
Risk Score ◽  
Genetic Risk ◽  
Disease Risk ◽  
Age Of Onset ◽  
Genetic Risk Score ◽  
Polygenic Risk Score ◽  
List Type ◽  
Dementia Risk ◽  
Incident Cases ◽  
Antagonistic Interactions

AbstractWe examined the associations between mitochondrial DNA haplogroups (MT-hg) and their interactions with a polygenic risk score based on nuclear-encoded mitochondrial genes (nMT-PRS) with risk of dementia and age of onset of dementia (AOO). Logistic regression was used to determine the effect of MT-hgs and nMT-PRS on dementia at baseline (332 controls / 204 cases). Cox proportional hazards models were used to model dementia AOO (n=1047; 433 incident cases). Additionally, we tested for interactions between MT-hg and nMT-PRS in the logistic and Cox models. MT-hg K and a one SD larger nMT-PRS were associated with elevated odds of dementia. Significant antagonistic interactions between the nMT-PRS and MT-hg K and T were observed. Individual MT-hg were not associated with AOO; however, a significant antagonistic interactions was observed between the nMT-PRS and MT-hg T and a synergistic interaction between the nMT-PRS and MT-hg V. These results suggest that MT-hgs influence dementia risk, and that variants in the nuclear and mitochondrial genome interact to influence the age of onset of dementia.HighlightsMitochondrial dysfunction has been proposed to influence dementia riskMT-hg K and T interacted with a genetic risk score to reduce dementia riskMT-hg T and V interacted with a genetic risk score to influence dementia age of onset

scholarly journals Alzheimer’s Genetic Risk Score linked to Incident Mild Behavioral Impairment

2017 ◽  
Author(s):  
Shea J. Andrews ◽  
Zahinoor Ismail ◽  
Kaarin J. Anstey ◽  
Moyra Mortby
Keyword(s):  
Cognitive Impairment ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Neuropsychiatric Symptoms ◽  
Later Life ◽  
Behavioral Impairment ◽  
Affective Dysregulation ◽  
Weighted Genetic Risk Score ◽  
Shared Risk

AbstractMild Behavioral Impairment (MBI) describes the emergence of later-life Neuropsychiatric Symptoms (NPS) as an at-risk state for cognitive decline and dementia and as a potential manifestation of prodromal dementia. How NPS mechanistically link to the development of Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD) is not fully understood. Potential mechanisms include either shared risk factors that are related to both NPS and cognitive impairment, or AD pathology promoting NPS. This is the first study to examine whether AD genetic loci, individually and as a genetic risk score, are a shared risk factor with MBI. 1377 older adults (aged 72-79; 738 males; 763 normal cognition) from the PATH Through Life project. MBI was assessed in accordance with Criterion 1 of the ISTAART-AA diagnostic criteria using the Neuropsychiatric Inventory. 25 LOAD risk loci were genotyped and a weighted genetic risk score (GRS) was constructed. Binomial logistic regression adjusting for age, gender, and education examined the association between LOAD GRS and MBI domains. An increase in the LOAD GRS and APOE*ε4 were associated with higher likelihood of Affective Dysregulation;MS4A4A-rs4938933*C andMS4A6A-rs610932*G were associated with a reduced likelihood of Affective Dysregulation;ZCWPW1-rs1476679*C was associated with a reduced likelihood of Social Inappropriateness and Abnormal Perception;BIN1-rs744373*G andEPHA1-rs11767557*C were associated with higher likelihood of Abnormal Perception;NME8-rs2718058*G was associated with a reduced likelihood Decreased Motivation. These findings suggest a common genetic etiology between MBI and traditionally recognized memory problems observed in AD and improve our understanding of the pathophysiological features underlying MBI.

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