scholarly journals A Weighted Genetic Risk Score Predicts Surgical Recurrence Independent of High-Risk Clinical Features in Dupuytren’s Disease

2019 ◽  
Vol 143 (2) ◽  
pp. 512-518 ◽  
Author(s):  
Sophie A. Riesmeijer ◽  
Oliver W. G. Manley ◽  
Michael Ng ◽  
Ilja M. Nolte ◽  
Dieuwke C. Broekstra ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Features ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Dupuytren’S Disease ◽  
Dupuytren's Disease ◽  
Surgical Recurrence ◽  
Weighted Genetic Risk Score

scholarly journals Identifying individuals with high risk of Alzheimer’s disease using polygenic risk scores

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ganna Leonenko ◽  
Emily Baker ◽  
Joshua Stevenson-Hoare ◽  
Annerieke Sierksma ◽  
Mark Fiers ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Genetic Risk ◽  
Prediction Accuracy ◽  
Genetic Risk Score ◽  
Low Risk ◽  
Risk Scores ◽  
Sample Mean ◽  
Polygenic Risk ◽  
Reliable Identification

AbstractPolygenic Risk Scores (PRS) for AD offer unique possibilities for reliable identification of individuals at high and low risk of AD. However, there is little agreement in the field as to what approach should be used for genetic risk score calculations, how to model the effect of APOE, what the optimal p-value threshold (pT) for SNP selection is and how to compare scores between studies and methods. We show that the best prediction accuracy is achieved with a model with two predictors (APOE and PRS excluding APOE region) with pT<0.1 for SNP selection. Prediction accuracy in a sample across different PRS approaches is similar, but individuals’ scores and their associated ranking differ. We show that standardising PRS against the population mean, as opposed to the sample mean, makes the individuals’ scores comparable between studies. Our work highlights the best strategies for polygenic profiling when assessing individuals for AD risk.

scholarly journals Evaluation of a weighted genetic risk score for the prediction of biomarkers of CYP2A6 activity

2019 ◽  
Vol 25 (1) ◽  
Author(s):  
Ahmed El‐Boraie ◽  
Taraneh Taghavi ◽  
Meghan J. Chenoweth ◽  
Koya Fukunaga ◽  
Taisei Mushiroda ◽  
...  
Keyword(s):  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Weighted Genetic Risk Score

scholarly journals Pregnancy does not modify the risk of MS in genetically susceptible women

2020 ◽  
Vol 7 (6) ◽  
pp. e898
Author(s):  
Cameron J. Adams ◽  
Sean L. Wu ◽  
Xiaorong Shao ◽  
Patrick T. Bradshaw ◽  
Edlin Gonzales ◽  
...  
Keyword(s):  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
The United States ◽  
Sensitivity Analyses ◽  
Risk Variants ◽  
Inverse Variance ◽  
Weighted Genetic Risk Score ◽  
Meta Analyses ◽  
Genetic Risk Variants

ObjectiveTo use the case-only gene-environment (G E) interaction study design to estimate interaction between pregnancy before onset of MS symptoms and established genetic risk factors for MS among White adult females.MethodsWe studied 2,497 female MS cases from 4 cohorts in the United States, Sweden, and Norway with clinical, reproductive, and genetic data. Pregnancy exposure was defined in 2 ways: (1) live birth pregnancy before onset of MS symptoms and (2) parity before onset of MS symptoms. We estimated interaction between pregnancy exposure and established genetic risk variants, including a weighted genetic risk score and both HLA and non-HLA variants, using logistic regression and proportional odds regression within each cohort. Within-cohort associations were combined using inverse variance meta-analyses with random effects. The case-only G × E independence assumption was tested in 7,067 individuals without MS.ResultsEvidence for interaction between pregnancy exposure and established genetic risk variants, including the strongly associated HLA-DRB1*15:01 allele and a weighted genetic risk score, was not observed. Results from sensitivity analyses were consistent with observed results.ConclusionOur findings indicate that pregnancy before symptom onset does not modify the risk of MS in genetically susceptible White females.

scholarly journals Burden of genetic risk variants in multiple sclerosis families in the Netherlands

2016 ◽  
Vol 2 ◽  
pp. 205521731664872 ◽  
Author(s):  
Julia Y Mescheriakova ◽  
Linda Broer ◽  
Simin Wahedi ◽  
André G Uitterlinden ◽  
Cornelia M van Duijn ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Weighted Genetic Risk Score ◽  
Sporadic Cases ◽  
Multiplex Families ◽  
The Difference ◽  
Multiple Sclerosis Patients ◽  
Genetic Burden

Background Approximately 20% of multiple sclerosis patients have a family history of multiple sclerosis. Studies of multiple sclerosis aggregation in families are inconclusive. Objective To investigate the genetic burden based on currently discovered genetic variants for multiple sclerosis risk in patients from Dutch multiple sclerosis multiplex families versus sporadic multiple sclerosis cases, and to study its influence on clinical phenotype and disease prediction. Methods Our study population consisted of 283 sporadic multiple sclerosis cases, 169 probands from multiplex families and 2028 controls. A weighted genetic risk score based on 102 non-human leukocyte antigen loci and HLA-DRB1*1501 was calculated. Results The weighted genetic risk score based on all loci was significantly higher in familial than in sporadic cases. The HLA-DRB1*1501 contributed significantly to the difference in genetic burden between the groups. A high weighted genetic risk score was significantly associated with a low age of disease onset in all multiple sclerosis patients, but not in the familial cases separately. The genetic risk score was significantly but modestly better in discriminating familial versus sporadic multiple sclerosis from controls. Conclusion Familial multiple sclerosis patients are more loaded with the common genetic variants than sporadic cases. The difference is mainly driven by HLA-DRB1*1501. The predictive capacity of genetic loci is poor and unlikely to be useful in clinical settings.

THU0010 A Weighted Genetic Risk Score Using 46 Loci to Predict Rheumatoid Arthritis Risk

2013 ◽  
Vol 72 (Suppl 3) ◽  
pp. A167.3-A168 ◽  
Author(s):  
A. Yarwood ◽  
M. Lunt ◽  
B. Han ◽  
S. Raychaudhuri ◽  
J. Bowes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Rheumatoid Arthritis Risk ◽  
Weighted Genetic Risk Score

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.

Abstract 18093: Bleeding Events in Clopidogrel-Treated Patients with STEMI is Associated with a Genetic Risk Score Based on High-Risk Genetic Polymorphisms

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jia-Hui Zhang ◽  
Jin-Qing Yuan ◽  
Xian-Min Meng ◽  
Xiao-Fang Tang ◽  
Jing Wang ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Major Bleeding ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Multivariate Logistic Regression Analysis ◽  
Bleeding Events ◽  
Genetic Score ◽  
Clinical Safety ◽  
Increased Risk

Introduction: Gene polymorphisms of ABCB1, CYP2C19, PON1 and P2Y12 may influence pharmacodynamics and clinical events of clopidogrel treatment. Hypothesis: We assessed the hypothesis that a genetic risk score based on identified high-risk single nucleotide polymorphisms (SNPs) would be associated with bleedings in clopidogrel-treated Chinese STEMI patients after percutaneous coronary intervention (PCI). Methods: A total of 503 consecutive patients with STEMI who received an uneventful PCI and were exposed to clopidogrel treatment for 12 months, were enrolled in the single-center registry. There were 38 tag SNPs selected from ABCB1, CYP2C19, PON1 and P2Y12 genes, which were detected by the ligase detection reaction. The primary clinical safety endpoint was the incidence of major bleeding events. Major bleeding was quantified according to bleeding academic research consortium definition (BARC) criteria, including type 3 and 5 in the analysis. The follow-up period was 12 months. Results: Overall, 46 BARC≥3 bleeding events (9.1%) occurred, which included 11 (2.1%) cases of BARC 3b bleedings and 35 (7.0%) cases of BARC 3a bleedings. After adjustment for traditional clinical risk factors, multivariate logistic regression analysis identified SNPs significantly associated with bleedings were ABCB1 (rs1045642, rs2235047, rs7779562), P2Y12 (rs6809699) and CYP2C19*17. A genetic risk score was constructed by summing the number of risk alleles. Bleedings were significantly associated with increased genetic risk score tertile. Patients in the top tertile of the genetic score were estimated to have a 3.268-fold (95%CI=1.198-8.929, p=0.021) increased risk of bleedings compared with those in the bottom tertile. As a continuous variable, the risk score resulted in an OR of 1.326 per unit increase in score (95%CI=1.098-1.601, p=0.003). Conclusions: This genetic score was significantly associated with bleedings after PCI in our study population.

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