Mo1615 POTENTIAL CLINICAL UTILITY OF SNP-BASED POLYGENIC RISK SCORE FOR DEVELOPING PERSONALIZED COLONOSCOPY SCREENING STRATEGY

2020 ◽  
Vol 158 (6) ◽  
pp. S-917
Author(s):  
Michael J. Northcutt ◽  
Michael K. Zijlstra ◽  
Ayush N. Shah ◽  
Mohammad Beig ◽  
Polina Imas ◽  
...  
Keyword(s):  
Risk Score ◽  
Clinical Utility ◽  
Screening Strategy ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Colonoscopy Screening ◽  
Potential Clinical Utility

scholarly journals A Comprehensive Screening Strategy of Breast Cancer Based on Different Penetrance Susceptibility Genes in Healthy Han Chinese Females

2021 ◽  
Author(s):  
Ling Hu ◽  
Chengbi Wu ◽  
Ping Liu ◽  
Lanbin Jiang ◽  
Yuntao Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Score ◽  
Screening Method ◽  
Susceptibility Genes ◽  
Screening Strategy ◽  
Han Chinese ◽  
Polygenic Risk Score ◽  
The West ◽  
Genetic Determination ◽  
Polygenic Risk

Abstract Background: Morbidity and mortality associated with breast cancer (BC) had increased rapidly in China. Early screening and intervention could greatly reduce the risk of hereditary BC. Several risk models had been utilized over the last decades to predict individual BC risk, but most of them didn’t assess the polygenic risk of low-penetrant genes. A novel screening method integrating different penetrance susceptibility genes was eagerly needed.Methods: Twenty-three variants of high and moderate penetrance susceptibility genes (HVs) and twenty loci of low penetrance susceptibility genes (LVs) were selected from previous studies. Genotyping of these mutations were conducted among 3777 healthy Han Chinese women (HCW) and 401 BC subjects. Based on the mutation profiles, we raised a comprehensive screening strategy using HVs and LVs to evaluate the polygenic risk score (PRS) in healthy individuals.Results: Three HVs in BRCA1, BRCA2 and PALB2 genes mutated in the study population, which suggests the necessity of applying genetic determination to healthy HCW. LVs were widely carried in objects and their frequencies differed greatly between HCW and the west population. After quality control and lasso dimension reduction, nineteen of twenty-three LVs were involved to construct a logistic regression model to evaluate the cumulative genetic risk score. The area under curve (AUC), sensitivity and specificity of the model is 0.993, 0.9676 and 0.9617 respectively, indicating that it is robust. Finally, a screening strategy using HVs and LVs was put forward to evaluate the risk of BC in normal objects.Conclusion: The distribution of HVs and LVs differed greatly between Han Chinese females and the west population. A screening strategy combining HVs and LVs showed strong efficacy in distinguishing high risk individuals from healthy women.Trial registration: ChiCTR, ChiCTR2000038558. Registered 24 September 2020 - Retrospectively 37 registered, http://www.chictr.org.cn/showproj.aspx?proj=60543

scholarly journals Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older

2021 ◽  
Author(s):  
Johannes T. Neumann ◽  
Moeen Riaz ◽  
Andrew Bakshi ◽  
Galina Polekhina ◽  
Le T.P. Thao ◽  
...  
Keyword(s):  
Risk Score ◽  
Cardiovascular Events ◽  
Prognostic Value ◽  
Clinical Utility ◽  
Polygenic Risk Score ◽  
Older Individuals ◽  
Conventional Model ◽  
Polygenic Risk ◽  
History Of ◽  
Genomic Risk

Background: The use of a polygenic risk score (PRS) to improve risk prediction of coronary heart disease (CHD) events has been demonstrated to have clinical utility in the general adult population. However, the prognostic value of a PRS for CHD has not been examined specifically in older populations of individuals aged ≥70 years, who comprise a distinct high-risk subgroup. The objective of this study was to evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of older individuals without a history of cardiovascular events. Methods: We used data from 12 792 genotyped, healthy older individuals enrolled into the ASPREE trial (Aspirin in Reducing Events in the Elderly), a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. Participants had no previous history of diagnosed atherothrombotic cardiovascular events, dementia, or persistent physical disability at enrollment. We calculated a PRS (meta-genomic risk score) consisting of 1.7 million genetic variants. The primary outcome was a composite of incident myocardial infarction or CHD death over 5 years. Results: At baseline, the median population age was 73.9 years, and 54.9% were female. In total, 254 incident CHD events occurred. When the PRS was added to conventional risk factors, it was independently associated with CHD (hazard ratio, 1.24 [95% CI, 1.08–1.42], P =0.002). The area under the curve of the conventional model was 70.53 (95% CI, 67.00–74.06), and after inclusion of the PRS increased to 71.78 (95% CI, 68.32–75.24, P =0.019), demonstrating improved prediction. Reclassification was also improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.15–0.28). Conclusion: A PRS for CHD performs well in older people and improves prediction over conventional cardiovascular risk factors. Our study provides evidence that genomic risk prediction for CHD has clinical utility in individuals aged 70 years and older. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01038583

scholarly journals Scores polygéniques et risque de cancer

2020 ◽  
Vol 36 (5) ◽  
pp. 535-537
Author(s):  
Bertrand Jordan
Keyword(s):  
Risk Assessment ◽  
Risk Score ◽  
Clinical Utility ◽  
Polygenic Risk Score ◽  
Cancer Type ◽  
Polygenic Risk

Risk assessment for a cancer type with moderate heritability can be accurately performed using a relatively small number of SNPs detected by GWAS analyses to calculate a polygenic risk score (PRS) that has definite clinical utility.

Polygenic risk score as clinical utility in psychiatry: a clinical viewpoint

2020 ◽  
Vol 66 (1) ◽  
pp. 53-60
Author(s):  
Masashi Ikeda ◽  
Takeo Saito ◽  
Tetsufumi Kanazawa ◽  
Nakao Iwata
Keyword(s):  
Risk Score ◽  
Clinical Utility ◽  
Polygenic Risk Score ◽  
Polygenic Risk

scholarly journals A polygenic risk score to predict future adult short stature amongst children

2021 ◽  
Author(s):  
Tianyuan Lu ◽  
Vincenzo Forgetta ◽  
Haoyu Wu ◽  
John R B Perry ◽  
Ken K Ong ◽  
...  
Keyword(s):  
Short Stature ◽  
Risk Score ◽  
Clinical Utility ◽  
Adult Height ◽  
European Ancestry ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Parental Height ◽  
The Uk

Abstract Context Adult height is highly heritable, yet no genetic predictor has demonstrated clinical utility compared to mid-parental height. Objective To develop a polygenic risk score for adult height and evaluate its clinical utility. Design A polygenic risk score was constructed based on meta-analysis of genome-wide association studies and evaluated on the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Subjects Participants included 442,599 genotyped White British individuals in the UK Biobank, and 941 genotyped child-parent trios of European ancestry in the ALSPAC cohort. Interventions None. Main Outcome Measures Standing height was measured using stadiometer; Standing height two standard deviations below the sex-specific population average was considered as short stature. Results Combined with sex, a polygenic risk score captured 71.1% of the total variance in adult height in the UK Biobank. In the ALSPAC cohort, the polygenic risk score was able to identify children who developed adulthood short stature with an area under the receiver operating characteristic curve (AUROC) of 0.84, which is close to that of mid-parental height. Combining this polygenic risk score with mid-parental height, or only one of the child’s parent’s height, could improve the AUROC to at most 0.90. The polygenic risk score could also substitute mid-parental height in age-specific Khamis-Roche height predictors and achieve an equally strong discriminative power in identifying children with a short stature in adulthood. Conclusions A polygenic risk score could be considered as an alternative or adjunct to mid-parental height to improve screening for children at risk of developing short stature in adulthood in European ancestry populations.

scholarly journals A/T/N polygenic risk score for cognitive decline in old age

2019 ◽  
Author(s):  
Annah M. Moore ◽  
Teresa J. Filshtein ◽  
Logan Dumitrescu ◽  
Amal Harrati ◽  
Fanny Elahi ◽  
...  
Keyword(s):  
Executive Function ◽  
Cognitive Decline ◽  
Risk Score ◽  
Genetic Risk ◽  
Clinical Utility ◽  
Association Studies ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Phosphorylated Tau ◽  
Polygenic Risk

AbstractINTRODUCTIONWe developed a novel polygenic risk score (PRS) based on the A/T/N (amyloid plaques (A), phosphorylated tau tangles (T), and neurodegeneration (N)) framework and compared a PRS based on clinical AD diagnosis to assess which was a better predictor of cognitive decline.METHODSWe used summary statistics from genome wide association studies of cerebrospinal fluid amyloid-β (Aβ42) and phosphorylated-tau (ptau181), left hippocampal volume (LHIPV), and late-onset AD dementia to calculate PRS for 1181 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Individual PRS were averaged to generate a composite A/T/N PRS. We assessed the association of PRS with baseline and longitudinal cognitive composites of executive function and memory.RESULTSThe A/T/N PRS showed superior predictive performance on AD biomarkers and executive function decline compared to the clinical AD PRS.DISCUSSIONResults suggest that integration of genetic risk across AD biomarkers may improve prediction of disease progression.Research in ContextSystematic ReviewAuthors reviewed relevant literature using PubMed and Google Scholar. Key studies that generated and validated polygenic risk scores (PRS) for clinical and pathologic AD were cited. PRS scores have been increasingly used in the literature but clinical utility continues to be questioned.InterpretationIn the current research landscape concerning PRS clinical utility in the AD space, there is room for model improvement and our hypothesis was that a PRS with integrated risk for AD biomarkers could yield a better model for cognitive decline.Future DirectionsThis study serves as proof-of-concept that encourages future study of integrated PRS across disease markers and utility in taking an A/T/N (amyloidosis, tauopathy and neurodegeneration) focused approach to genetic risk for cognitive decline and AD.

scholarly journals A Comprehensive Screening Strategy of Breast Cancer Based on Different Penetrance Susceptibility Genes in Healthy Han Chinese Females

2020 ◽  
Author(s):  
Ling Hu ◽  
Chengbi Wu ◽  
Ping Liu ◽  
Lanbin Jiang ◽  
Yuntao Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Score ◽  
Screening Method ◽  
Susceptibility Genes ◽  
Screening Strategy ◽  
Han Chinese ◽  
Polygenic Risk Score ◽  
The West ◽  
Genetic Determination ◽  
Polygenic Risk

Abstract Background: Morbidity and mortality associated with breast cancer (BC) had increased rapidly in China. Early screening and intervention could greatly reduce the risk of hereditary BC. Several risk models had been utilized over the last decades to predict individual BC risk, but most of them didn’t assess the polygenic risk of low-penetrant genes. A novel screening method integrating different penetrance susceptibility genes was eagerly needed.Methods: Twenty-three variants of high and moderate penetrance susceptibility genes (HVs) and twenty loci of low penetrance susceptibility genes (LVs) were selected from previous studies. Genotyping of these mutations were conducted among 3777 healthy Chinese Han women and 401 BC subjects. Based on the mutation profiles, we raised a comprehensive screening strategy using HVs and LVs to evaluate the polygenic risk score (PRS) in healthy individuals.Results: Three HVs in BRCA1, BRCA2 and PALB genes mutated in the study population, which suggests the necessity of applying genetic determination to healthy Han Chinese women. LVs were widely carried in objects and their frequencies differed greatly between Han Chinese females and the west population. After quality control and lasso dimension reduction, nineteen of twenty-three LVs were involved to construct a logistic regression model to evaluate the cumulative genetic risk score. The area under curve (AUC), sensitivity and specificity of the model is 0.993, 0.9676 and 0.9617 respectively, indicating that it is robust. Finally, a screening strategy using HVs and LVs was put forward to evaluate the risk of BC in normal objects.Conclusions: The distribution of HVs and LVs differed greatly between Han Chinese females and the west population. A screening strategy combining HVs and LVs showed strong efficacy in distinguishing high risk individuals from healthy women.Trial registration: ChiCTR, ChiCTR2000038558. Registered 24 September 2020 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=60543

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