826 – Polygenic Risk Score, Family History, and Colorectal Cancer by Molecular Subtypes

2019 ◽  
Vol 156 (6) ◽  
pp. S-178
Author(s):  
Long H. Nguyen ◽  
Kathryn Penney ◽  
Amit D. Joshi ◽  
Yin Cao ◽  
Mingyang Song ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Risk Score ◽  
Molecular Subtypes ◽  
Polygenic Risk Score ◽  
Polygenic Risk

scholarly journals Relative contributions of family history and a polygenic risk score on COPD and related outcomes: COPDGene and ECLIPSE studies

2020 ◽  
Vol 7 (1) ◽  
pp. e000755
Author(s):  
Matthew Moll ◽  
Sharon M. Lutz ◽  
Auyon J. Ghosh ◽  
Phuwanat Sakornsakolpat ◽  
Craig P. Hersh ◽  
...  
Keyword(s):  
Family History ◽  
Risk Score ◽  
Characteristic Curve ◽  
Significant Proportion ◽  
Chronic Obstructive ◽  
Polygenic Risk Score ◽  
Positive Interaction ◽  
Polygenic Risk ◽  
Mediation Analyses ◽  
The Impact

IntroductionFamily history is a risk factor for chronic obstructive pulmonary disease (COPD). We previously developed a COPD risk score from genome-wide genetic markers (Polygenic Risk Score, PRS). Whether the PRS and family history provide complementary or redundant information for predicting COPD and related outcomes is unknown.MethodsWe assessed the predictive capacity of family history and PRS on COPD and COPD-related outcomes in non-Hispanic white (NHW) and African American (AA) subjects from COPDGene and ECLIPSE studies. We also performed interaction and mediation analyses.ResultsIn COPDGene, family history and PRS were significantly associated with COPD in a single model (PFamHx <0.0001; PPRS<0.0001). Similar trends were seen in ECLIPSE. The area under the receiver operator characteristic curve for a model containing family history and PRS was significantly higher than a model with PRS (p=0.00035) in NHWs and a model with family history (p<0.0001) alone in NHWs and AAs. Both family history and PRS were significantly associated with measures of quantitative emphysema and airway thickness. There was a weakly positive interaction between family history and the PRS under the additive, but not multiplicative scale in NHWs (relative excess risk due to interaction=0.48, p=0.04). Mediation analyses found that a significant proportion of the effect of family history on COPD was mediated through PRS in NHWs (16.5%, 95% CI 9.4% to 24.3%), but not AAs.ConclusionFamily history and the PRS provide complementary information for predicting COPD and related outcomes. Future studies can address the impact of obtaining both measures in clinical practice.

scholarly journals Non-Lynch Familial and Early-Onset Colorectal Cancer Explained by Accumulation of Low-Risk Genetic Variants

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3857
Author(s):  
Pilar Mur ◽  
Nuria Bonifaci ◽  
Anna Díez-Villanueva ◽  
Elisabet Munté ◽  
Maria Henar Alonso ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Score ◽  
Early Onset ◽  
Low Risk ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Pathogenic Variants ◽  
Predisposing Genes ◽  
The Mean ◽  
Early Onset Colorectal Cancer

A large proportion of familial and/or early-onset cancer patients do not carry pathogenic variants in known cancer predisposing genes. We aimed to assess the contribution of previously validated low-risk colorectal cancer (CRC) alleles to familial/early-onset CRC (fCRC) and to serrated polyposis. We estimated the association of CRC with a 92-variant-based weighted polygenic risk score (wPRS) using 417 fCRC patients, 80 serrated polyposis patients, 1077 hospital-based incident CRC patients, and 1642 controls. The mean wPRS was significantly higher in fCRC than in controls or sporadic CRC patients. fCRC patients in the highest (20th) wPRS quantile were at four-fold greater CRC risk than those in the middle quantile (10th). Compared to low-wPRS fCRC, a higher number of high-wPRS fCRC patients had developed multiple primary CRCs, had CRC family history, and were diagnosed at age ≥50. No association with wPRS was observed for serrated polyposis. In conclusion, a relevant proportion of mismatch repair (MMR)-proficient fCRC cases might be explained by the accumulation of low-risk CRC alleles. Validation in independent cohorts and development of predictive models that include polygenic risk score (PRS) data and other CRC predisposing factors will determine the implementation of PRS into genetic testing and counselling in familial and early-onset CRC.

Abstract 881: Benchmarking genome-wide polygenic risk score development techniques in colorectal cancer risk prediction

2021 ◽  
Author(s):  
Minta Thomas ◽  
Lori C Sakoda ◽  
Jeffrey K Lee ◽  
Mark A Jenkins ◽  
Andrea Burnett-Hartman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Risk Prediction ◽  
Risk Score ◽  
Colorectal Cancer Risk ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Genome Wide

scholarly journals Polygenic Risk Score is a Predictor of Adenomatous Polyps at Screening Colonoscopy

2020 ◽  
Author(s):  
Michael Northcutt ◽  
Zhuqing Shi ◽  
Michael Zijlstra ◽  
Ayush Shah ◽  
Siqun Zheng ◽  
...  
Keyword(s):  
Family History ◽  
Risk Score ◽  
Genetic Risk Score ◽  
Positive Family History ◽  
Snp Array ◽  
Adenomatous Polyps ◽  
Screening Colonoscopy ◽  
Polygenic Risk Score ◽  
Average Risk ◽  
Polygenic Risk

Abstract Background: Single nucleotide polymorphism (SNP)-based polygenic risk scoring is predictive of colorectal cancer (CRC) risk. However, few studies have investigated the association of genetic risk score (GRS) with detection of adenomatous polyps at screening colonoscopy. Methods: We randomly selected 1,769 Caucasian subjects who underwent screening colonoscopy from the Genomic Health Initiative (GHI), a biobank of NorthShore University HealthSystem. Outcomes from initial screening colonoscopy were recorded. Twenty-two CRC risk-associated SNPs were obtained from the Affymetrix™ SNP array and used to calculate an odds ratio (OR)-weighted and population-standardized GRS. Subjects with GRS of <0.5, 0.5-1.5, and >1.5 were categorized as low, average and elevated risk.Results: Among 1,769 subjects, 520 (29%) had 1 or more adenomatous polyps. GRS was significantly higher in subjects with adenomatous polyps than those without; mean (95% confidence interval) was 1.02 (1.00-1.05) and 0.97 (0.95-0.99), respectively, p<0.001. The association remained significant after adjusting for age, gender, body mass index, and family history, p<0.001. The detection rate of adenomatous polyps was 10.8%, 29.0% and 39.7% in subjects with low, average and elevated GRS, respectively, p-trend <0.001. Higher GRS was also associated with early age diagnosis of adenomatous polyps, p<0.001. In contrast, positive family history was not associated with risk and age of adenomatous polyps.Conclusions: GRS was significantly associated with adenomatous polyps in subjects undergoing screening colonoscopy. This result may help in stratifying average risk patients and facilitating personalized colonoscopy screening strategies.

scholarly journals Polygenic Risk Score, Parental Socioeconomic Status, Family History of Psychiatric Disorders, and the Risk for Schizophrenia

2015 ◽  
Vol 72 (7) ◽  
pp. 635 ◽  
Author(s):  
Esben Agerbo ◽  
Patrick F. Sullivan ◽  
Bjarni J. Vilhjálmsson ◽  
Carsten B. Pedersen ◽  
Ole Mors ◽  
...  
Keyword(s):  
Socioeconomic Status ◽  
Family History ◽  
Psychiatric Disorders ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
History Of ◽  
Parental Socioeconomic Status

scholarly journals Precision Colorectal Cancer Screening with Polygenic Risk Score

2020 ◽  
Author(s):  
Tonis Tasa ◽  
Mikk Puustusmaa ◽  
Neeme Tonisson ◽  
Berit Kolk ◽  
Peeter Padrik
Keyword(s):  
Colorectal Cancer ◽  
Risk Score ◽  
Association Studies ◽  
Absolute Risk ◽  
Specific Model ◽  
Background Information ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Polygenic Risk ◽  
Common Cancer

Colorectal cancer (CRC) is the second most common cancer in women and third most common cancer in men. Genome-wide association studies have identified numerous genetic variants (SNPs) independently associated with CRC. The effects of such SNPs can be combined into a single polygenic risk score (PRS). Stratification of individuals according to PRS could be introduced to primary and secondary prevention. Our aim was to combine risk stratification of a sex-specific PRS model with recommendations for individualized CRC screening. Previously published PRS models for predicting the risk of CRC were collected from the literature. These were validated on the UK Biobank (UKBB) consisting of a total of 458 696 quality-controlled genotypes with 1810 and 1348 prevalent male cases, and 2410 and 1810 incident male and female cases. The best performing sex-specific model was selected based on the AUC in prevalent data and independently validated in the incident dataset. Using Estonian CRC background information, we performed absolute risk simulations and examined the ability of PRS in risk stratifying individual screening recommendations. The best-performing model included 91 SNPs. The C-index of the best performing model in the dataset was 0.613 (SE = 0.007) and hazard ratio (HR) per unit of PRS was 1.53 (1.47 - 1.59) for males. Respective metrics for females were 0.617 (SE = 0.006) and 1.50 (1.44 - 1.58). PRS risk simulations showed that a genetically average 50-year-old female doubles her risk by age 58 (55 in males) and triples it by age 63 (59 in males). In addition, the best performing PRS model was able to identify individuals in one of seven groups proposed by Naber et al. for different coloscopy screening recommendation regimens. We have combined PRS-based recommendations for individual screening attendance. Our approach is easily adaptable to other nationalities by using population-specific background data of other genetically similar populations.

scholarly journals Capturing additional genetic risk from family history for improved polygenic risk prediction

2022 ◽  
Author(s):  
Tianyuan Lu ◽  
Vincenzo Forgetta ◽  
J Brent Richards ◽  
Celia MT Greenwood
Keyword(s):  
Family History ◽  
Risk Prediction ◽  
Risk Score ◽  
Genetic Risk ◽  
Adult Height ◽  
Prediction Models ◽  
European Ancestry ◽  
Polygenic Risk Score ◽  
Parental History ◽  
Polygenic Risk

Family history of complex traits may reflect transmitted rare pathogenic variants, intrafamilial shared exposures to environmental and lifestyle factors, as well as a common genetic predisposition. We developed a latent factor model to quantify trait heritability in excess of that captured by a common variant-based polygenic risk score, but inferable from family history. We applied our model to predict adult height for 941 children in the Avon Longitudinal Study of Parents and Children cohort as well as 11 complex diseases for ~400,000 European ancestry participants in the UK Biobank. Parental history brought consistent significant improvements in the predictive power of polygenic risk prediction. For instance, a joint predictor was able to explain ~55% of the total variance in sex-adjusted adult height z-scores, close to the estimated heritability. Our work showcases an innovative paradigm for risk calculation, and supports incorporation of family history into polygenic risk score-based genetic risk prediction models.

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