scholarly journals Multi-ethnic polygenic risk modifies the association between APOL1 high risk genotypes and chronic kidney disease

2021 ◽  
Author(s):  
Ha My T. Vy ◽  
Faris F. Gulamali ◽  
Benjamin Glicksberg ◽  
Orlando Gutierrez ◽  
Richard Cooper ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
High Risk ◽  
Kidney Disease ◽  
Risk Score ◽  
Hispanic Americans ◽  
Polygenic Risk Score ◽  
Advanced Chronic Kidney Disease ◽  
Polygenic Risk ◽  
Improve Risk Stratification ◽  
Increase Risk

The burden of advanced chronic kidney disease (CKD) falls disproportionately on minorities including African Americans (AAs) and Hispanic Americans (HAs) with admixed ancestry. Even though APOL1 high-risk genotypes increase risk of kidney disease, their penetrance is incomplete, indicating that the modification of APOL1 high risk may be polygenic. For this study, we used three multi-ethnic cohorts with APOL1 high risk genotypes and calculated a multi-ethnic PRS using publicly available summary statistics. We show that CKD risk is significantly modified by a multi-ethnic polygenic risk score. Standardizing population screening for CKD by including APOL1 high-risk genotypes and polygenic risk score may improve risk stratification and outcomes.

scholarly journals Polygenic risk for schizophrenia, transition and cortical gyrification: a high-risk study

2017 ◽  
Vol 48 (9) ◽  
pp. 1532-1539 ◽  
Author(s):  
E. Neilson ◽  
C. Bois ◽  
T.-K. Clarke ◽  
L. Hall ◽  
E. C. Johnstone ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Familial Risk ◽  
Positive Association ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Score Analysis ◽  
Increased Risk ◽  
Heritable Disorder ◽  
Diagnostic Symptoms

AbstractBackgroundSchizophrenia is a highly heritable disorder, linked to several structural abnormalities of the brain. More specifically, previous findings have suggested that increased gyrification in frontal and temporal regions are implicated in the pathogenesis of schizophrenia.MethodsThe current study included participants at high familial risk of schizophrenia who remained well (n= 31), who developed sub-diagnostic symptoms (n= 28) and who developed schizophrenia (n= 9) as well as healthy controls (HC) (n= 16). We first tested whether individuals at high familial risk of schizophrenia carried an increased burden of trait-associated alleles using polygenic risk score analysis. We then assessed the extent to which polygenic risk was associated with gyral folding in the frontal and temporal lobes.ResultsWe found that individuals at high familial risk of schizophrenia who developed schizophrenia carried a significantly greater burden of risk-conferring variants for the disorder compared to those at high risk (HR) who developed sub-diagnostic symptoms or remained well and HC. Furthermore, within the HR cohort, there was a significant and positive association between schizophrenia polygenic risk score and bilateral frontal gyrification.ConclusionsThese results suggest that polygenic risk for schizophrenia impacts upon early neurodevelopment to confer greater gyral folding in adulthood and an increased risk of developing the disorder.

Polygenic risk score for breast cancer in high-risk women.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 1508-1508 ◽  
Author(s):  
Mary Helen Black ◽  
Shuwei Li ◽  
Holly LaDuca ◽  
Jefferey Chen ◽  
Robert Hoiness ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
High Risk Women

T80SCHIZOPHRENIA POLYGENIC RISK SCORE CORRELATES WITH DECREASED COGNITIVE FUNCTIONS IN ULTRA-HIGH-RISK INDIVIDUALS FOR PSYCHOSIS

2019 ◽  
Vol 29 ◽  
pp. S258-S259
Author(s):  
Qin He ◽  
Oussama Kebir ◽  
Gabrielle Houle ◽  
Calwing Liao ◽  
Patrick A. Dion ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Cognitive Functions ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Ultra High Risk

scholarly journals Serum Urate Polygenic Risk Score Can Improve Gout Risk Prediction: A Large-Scale Cohort Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanfei Zhang ◽  
Ming Ta Michael Lee
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Large Scale ◽  
Characteristic Curve ◽  
Model Performance ◽  
Serum Urate ◽  
Lifestyle Changes ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Risk Patients

Gout is a painful inflammatory arthritis affecting more than 8 million Americans. Identifying high-risk patients in early life could potentially encourage people to adopt lifestyle changes to prevent gout. Polygenic risk score (PRS) provides an overall estimate of an individual's genetic liability to develop a disease and can be used for early identification of high-risk individuals. In this study, we validated a previously reported PRS in an independent cohort. The urate-PRS was constructed from 110 significant urate-associated variants identified in Europeans. Phenome-wide and PRS-wide association study showed the urate-PRS is highly specifically associated with gout (phecode: 274.10; beta = 1.495 [1.372, 1.619], p = 4.37e-124). Urate-PRS alone did not performed in the gout prediction (area under the receiver operating characteristic curve, AUROC = 0.640); however, the addition of PRS upon demographics significantly improved the model performance, yielding an AUROC of 0.804 from 0.777 (DeLong test p = 3.66e−9). Trans-ethnic PRS and European-specific PRS showed similar prediction performance. We observed increasing gout prevalence and odds ratio (OR) across the PRS quintiles. Our study showed 8.2% of the cohort had more than 2.5 odds for gout than remainders, indicating that urate-PRS may be a better marker than age and sex to stratify patient risk. With the rapid growth of large biorepositories, such as All of Us, urate-PRS can be applied quickly and widely in population to estimate individual's risk, providing a powerful tool for gout preventive purpose in population health.

scholarly journals Polygenic risk for aggressive behaviour from late childhood through early adulthood

2021 ◽  
Author(s):  
Tina Kretschmer ◽  
Isabelle Ouellet-Morin ◽  
Charlotte Vrijen ◽  
Ilja Maria Nolte ◽  
Catharina A. Hartman
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Genetic Information ◽  
Aggressive Behaviour ◽  
Population Sample ◽  
Genome Wide Association ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Polygenic Risk ◽  
Genome Wide

Twin studies suggest a substantial role for genes in explaining individual differences in aggressive behaviour across development. It is unclear, however, how directly measured genetic risk is associated with aggressive behaviour at different moments across adolescence and how genes might distinguish developmental trajectories of aggressive behaviour. Here, a polygenic risk score derived from the EAGLE-Consortium genome-wide association study of aggressive behaviour in children was tested as predictor of latent growth classes derived from those measures in an adolescent population (n = 2229, of which n = 1259 with genetic information) and a high-risk sample (n = 543, of which n = 339 with genetic information). In the population sample, the polygenic risk score explained variation in parent-reported aggressive behaviour at all ages and distinguished between stable low aggressive behaviour and moderate and high-decreasing trajectories based on parent-report. In contrast, the polygenic risk score was not associated with self- and teacher-reported aggressive behaviour, and no associations were found in the high-risk sample. This pattern of results suggests that methodological choices made in genome-wide association studies impact the predictive power of polygenic risk scores, not just with respect to power but likely also in terms of generalizability and specificity.

scholarly journals Accurate Prediction Model - Polygenic Risk Score for High-Risk Individuals Predictive of Gastric Cancer

2021 ◽  
Author(s):  
Fujiao Duan ◽  
Chunhua Song ◽  
Peng Wang ◽  
Hua Ye ◽  
Liping Dai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Factors ◽  
Prediction Models ◽  
Information Criterion ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
H Pylori

Abstract Background The genetic variation of gastric cancer has not been fully identified. We aimed to screen and identify common variant single nucleotide polymorphisms (SNPs) and long noncoding RNA (lncRNA) related SNPs associated with the risk of gastric cancer, and construct and evaluate prediction models based on polygenic risk score (PRS). Methods Non-genetic factors such as H.pylori infection, environment, and genetic factors associated with gastric cancer were screened following meta-analysis and bioinformatics,verified by frequency matched case-control study. PRS and weighted genetic risk scores (wGRS) were derived from estimation of effect size. Net reclassification improvement (NRI), integrated discrimination improvement (IDI), akaike information criterion (AIC) and bayesian information criterion (BIC) were used to evaluate model. Results A risk gradient was observed across quantile of the PRS, the results showed that the risk of gastric cancer in the highest 10 quantile of PRS was 3.24 folds higher than that of the general population (OR=3.24,95%CI: 2.07, 5.06). The PRS with one or more risk factors (smoking, drinking and H. pylori infection) was superior to the single genetic risk model. For NRI and IDI, the PRS combinations were significantly improved compared to wGRS model combinations (P<0.001). The model of PRS combined with lncRNA SNPs, smoking, drinking and H. pylori infection was the best fitting model (AIC=117.23, BIC=122.31). Conclusion Our findings indicated that the model based on PRS combined with lncRNA SNPs, smoking, drinking, and H. pylori infection had the optimal predictive ability on the risk of gastric cancer, contributing to distinguish high-risk groups from population.

Thrombolysis In Myocardial Infarction (TIMI) Risk Score and Mortality in Patients With Advanced Chronic Kidney Disease and on Dialysis

2009 ◽  
Vol 103 (11) ◽  
pp. 1513-1517 ◽  
Author(s):  
Usman Baber ◽  
Annapoorna S. Kini ◽  
Samin K. Sharma ◽  
Michael C. Kim ◽  
Michael E. Farkouh ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Risk Score ◽  
Advanced Chronic Kidney Disease ◽  
Timi Risk Score
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