Five-year absolute risk estimates of colorectal cancer based on CCRAT model and polygenic risk scores: a validation study using the Quebec population-based cohort CARTaGENE

ObjectivePolygenic risk scores (PRSs) are used to quantify the cumulative effects of a number of genetic variants, which may individually have a very small effect on susceptibility to a disease; we used PRSs to better understand the genetic contribution to common epilepsy and its subtypes.MethodsWe first replicated previous single associations using 373 unrelated patients. We then calculated PRSs in the same French Canadian patients with epilepsy divided into 7 epilepsy subtypes and population-based controls. We fitted a logistic mixed model to calculate the variance explained by the PRS using pseudo-R2 statistics.ResultsWe show that the PRS explains more of the variance in idiopathic generalized epilepsy than in patients with nonacquired focal epilepsy. We also demonstrate that the variance explained is different within each epilepsy subtype.ConclusionsGlobally, we support the notion that PRSs provide a reliable measure to rightfully estimate the contribution of genetic factors to the pathophysiologic mechanism of epilepsies, but further studies are needed on PRSs before they can be used clinically.

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Jumping to conclusions, general intelligence, and psychosis liability: findings from the multi-centre EU-GEI case-control study

Psychological Medicine ◽

10.1017/s003329171900357x ◽

2020 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Giada Tripoli ◽

Diego Quattrone ◽

Laura Ferraro ◽

Charlotte Gayer-Anderson ◽

Victoria Rodriguez ◽

...

Keyword(s):

Cognitive Biases ◽

Population Based ◽

Case Control ◽

Risk Scores ◽

First Episode ◽

Polygenic Risk Score ◽

General Intelligence ◽

Polygenic Risk ◽

Jumping To Conclusions ◽

Episode Psychosis

Abstract Background The ‘jumping to conclusions’ (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ. Methods A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia. Results The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients. Conclusions Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.

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Predicting the absolute risk of dying from colorectal cancer and from other causes using population-based cancer registry data

Statistics in Medicine ◽

10.1002/sim.4454 ◽

2011 ◽

Vol 31 (5) ◽

pp. 489-500 ◽

Cited By ~ 11

Author(s):

Minjung Lee ◽

Kathleen A. Cronin ◽

Mitchell H. Gail ◽

Eric J. Feuer

Keyword(s):

Colorectal Cancer ◽

Cancer Registry ◽

Absolute Risk ◽

Population Based ◽

Registry Data ◽

Cancer Registry Data ◽

The Absolute

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Two schizophrenia imaging signatures and their associations with cognition, psychopathology, and genetics in the general population

10.1101/2022.01.07.22268854 ◽

2022 ◽

Author(s):

Ganesh B Chand ◽

Pankhuri Singhal ◽

Dominic B Dwyer ◽

Junhao Wen ◽

Guray Erus ◽

...

Keyword(s):

Genetic Risk ◽

Gray Matter Volume ◽

Control Sample ◽

Population Level ◽

Population Based ◽

Risk Scores ◽

Support Vector ◽

Cross Sectional ◽

Polygenic Risk ◽

Independent Population

The prevalence and significance of schizophrenia-related phenotypes at the population-level are debated in the literature. Here we assess whether two recently reported neuroanatomical signatures of schizophrenia, signature 1 with widespread reduction of gray matter volume, and signature 2 with increased striatal volume, could be replicated in an independent schizophrenia sample, and investigate whether expression of these signatures can be detected at the population-level and how they relate to cognition, psychosis spectrum symptoms, and schizophrenia genetic risk. This cross-sectional study used an independent schizophrenia-control sample (n=347; age 16-57 years) for replication of imaging signatures, and then examined two independent population-level datasets: Philadelphia Neurodevelopmental Cohort [PNC; n=359 typically developing (TD) and psychosis-spectrum symptoms (PS) youth] and UK Biobank (UKBB; n=836; age 44-50 years) adults. We quantified signature expression using support-vector machine learning, and compared cognition, psychopathology, and polygenic risk between signatures. Two neuroanatomical signatures of schizophrenia were replicated. Signature 1 but not signature 2 was significantly more common in youth with PS than TD youth, whereas signature 2 frequency was similar. In both youth and adults, signature 1 had worse cognitive performance than signature 2. Compared to adults with neither signature, adults expressing signature 1 had elevated schizophrenia polygenic risk scores, but this was not seen for signature 2. We successfully replicate two neuroanatomical signatures of schizophrenia, and describe their prevalence in population-based samples of youth and adults. We further demonstrate distinct relationships of these signatures with psychosis symptoms, cognition, and genetic risk, potentially reflecting underlying neurobiological vulnerability.

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Estimation of Absolute Risk of Colorectal Cancer Based on Healthy Lifestyle, Genetic Risk, and Colonoscopy Status in a Population-Based Study

Gastroenterology ◽

10.1053/j.gastro.2020.03.016 ◽

2020 ◽

Vol 159 (1) ◽

pp. 129-138.e9 ◽

Cited By ~ 2

Author(s):

Prudence R. Carr ◽

Korbinian Weigl ◽

Dominic Edelmann ◽

Lina Jansen ◽

Jenny Chang-Claude ◽

...

Keyword(s):

Colorectal Cancer ◽

Genetic Risk ◽

Healthy Lifestyle ◽

Absolute Risk ◽

Population Based ◽

Population Based Study

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Risk of Synchronous and Metachronous Colorectal Cancer: Population-Based Estimates in Denmark with Focus on Non-Hereditary Cases Diagnosed After Age 50

Scandinavian Journal of Surgery ◽

10.1177/1457496918798212 ◽

2018 ◽

Vol 108 (2) ◽

pp. 152-158 ◽

Cited By ~ 4

Author(s):

L. J. Lindberg ◽

S. Ladelund ◽

I. Bernstein ◽

C. Therkildsen ◽

M. Nilbert

Keyword(s):

Colorectal Cancer ◽

Environmental Factors ◽

Absolute Risk ◽

Tumor Location ◽

Population Based ◽

Incidence Rates ◽

Increased Risk ◽

Synchronous Colorectal Cancer ◽

Metachronous Colorectal Cancer ◽

Rate Ratios

Background and Aims: The risk of synchronous and metachronous colorectal cancer is influenced by heritable and environmental factors. As a basis for comparative studies, we provide population-based estimates of synchronous and metachronous colorectal cancer with a focus on non-heritable cases. Material and Methods: Based on data from national Danish cancer registers, we estimated the proportion of synchronous colorectal cancer and the incidence rates and risks for metachronous colorectal cancer in 28,504 individuals, who developed 577 metachronous colorectal cancer above age 50. Results: Synchronous colorectal cancer was diagnosed in 1.3% of the cases. The risk of metachronous colorectal cancer was associated with sex, tumor location, and age with the strongest influence from the latter. The incidence rate ratios for metachronous colorectal cancer ranged from above 6 in patients below age 65 to <1–3.2 in patients above age 65. The absolute risk of metachronous colorectal cancer was ⩾10% in patients below age 65 and 1.0%–8.0% in patients above age 65. Conclusion: Individuals who develop sporadic, non-inherited colorectal cancer above age 50 are at a significantly increased risk of metachronous colorectal cancer with risk estimates that are strongly affected by age. This observation underscores the need for development of targeted surveillance in the most common clinical subset of colorectal cancer.

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Colorectal Cancer Risk Prediction Tool for White Men and Women Without Known Susceptibility

Journal of Clinical Oncology ◽

10.1200/jco.2008.17.4797 ◽

2009 ◽

Vol 27 (5) ◽

pp. 686-693 ◽

Cited By ~ 146

Author(s):

Andrew N. Freedman ◽

Martha L. Slattery ◽

Rachel Ballard-Barbash ◽

Gordon Willis ◽

Bette J. Cann ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Prediction ◽

Leisure Time ◽

Vegetable Consumption ◽

Absolute Risk ◽

Population Based ◽

Vigorous Activity ◽

Men And Women ◽

Relative Risks ◽

History Of

Purpose Given the high incidence of colorectal cancer (CRC), and the availability of procedures that can detect disease and remove precancerous lesions, there is a need for a model that estimates the probability of developing CRC across various age intervals and risk factor profiles. Methods The development of separate CRC absolute risk models for men and women included estimating relative risks and attributable risk parameters from population-based case-control data separately for proximal, distal, and rectal cancer and combining these estimates with baseline age-specific cancer hazard rates based on Surveillance, Epidemiology, and End Results (SEER) incidence rates and competing mortality risks. Results For men, the model included a cancer-negative sigmoidoscopy/colonoscopy in the last 10 years, polyp history in the last 10 years, history of CRC in first-degree relatives, aspirin and nonsteroidal anti-inflammatory drug (NSAID) use, cigarette smoking, body mass index (BMI), current leisure-time vigorous activity, and vegetable consumption. For women, the model included sigmoidoscopy/colonoscopy, polyp history, history of CRC in first-degree relatives, aspirin and NSAID use, BMI, leisure-time vigorous activity, vegetable consumption, hormone-replacement therapy (HRT), and estrogen exposure on the basis of menopausal status. For men and women, relative risks differed slightly by tumor site. A validation study in independent data indicates that the models for men and women are well calibrated. Conclusion We developed absolute risk prediction models for CRC from population-based data, and a simple questionnaire suitable for self-administration. This model is potentially useful for counseling, for designing research intervention studies, and for other applications.

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Polygenic risk for psychiatric disorder reveals distinct association profiles across social behaviour in the general population

10.1101/2021.06.28.21259532 ◽

2021 ◽

Author(s):

Fenja Schlag ◽

Andrea Giuseppe Allegrini ◽

Jan Buitelaar ◽

Ellen Verhoef ◽

Marjolein van Donkelaar ◽

...

Keyword(s):

General Population ◽

Psychiatric Disorders ◽

Social Behaviour ◽

Negative Binomial ◽

Random Effect ◽

Population Based ◽

Autism Spectrum ◽

Risk Scores ◽

Polygenic Risk ◽

Shared Genetic

Many complex psychiatric disorders are characterised by a spectrum of social difficulties. These symptoms lie on a behavioural dimension that is shared with social behaviour in the general population, with substantial contributions of genetic factors. However, shared genetic links may vary across psychiatric disorders and social symptoms. Here, we systematically investigate heterogeneity in shared genetic liabilities with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), bipolar disorder (BP), major depression (MD) and schizophrenia, across a spectrum of different social symptoms. Specifically, longitudinally assessed low-prosociality and peer-problem scores in two UK population-based/community-based cohorts (ALSPAC, N ≤ 6174, 4-17 years; TEDS, N ≤ 7112, 4-16 years; parent- and teacher-reports) were regressed on polygenic risk scores for ADHD, ASD, BP, MD, and schizophrenia, as informed by genome-wide summary statistics from large consortia, using negative binomial regression models. Across ALSPAC and TEDS, we replicated univariate polygenic associations between social behaviour and risk for ADHD, MD, and schizophrenia. Modelling univariate genetic effects across both cohorts with random-effect meta-regression revealed evidence for polygenic links between social behaviour and ADHD, ASD, MD, and schizophrenia risk, but not BP, where differences in age, reporter and social trait captured 45-88% in univariate effect variation. For ADHD, MD, and ASD polygenic risk, we identified stronger association with peer problems than low prosociality, while schizophrenia polygenic risk was solely associated with low prosociality. The identified association profiles suggest marked differences in the social genetic architecture underlying different psychiatric disorders when investigating population-based social symptoms across 13 years of child and adolescent development.

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Jumping To Conclusions, General Intelligence, And Psychosis Liability: Findings From The Multi-Centre EU-GEI Case-Control Study

10.1101/634352 ◽

2019 ◽

Author(s):

Giada Tripoli ◽

Diego Quattrone ◽

Laura Ferraro ◽

Charlotte Gayer-Anderson ◽

Victoria Rodriguez ◽

...

Keyword(s):

Probabilistic Reasoning ◽

Cognitive Biases ◽

Population Based ◽

Case Control ◽

Risk Scores ◽

Polygenic Risk Score ◽

General Intelligence ◽

Polygenic Risk ◽

Jumping To Conclusions ◽

Beads Task

AbstractBackgroundThe “jumping to conclusions” (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.Methods817 FEP patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC (assessed by the number of beads drawn on the probabilistic reasoning “beads” task) and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.ResultsThe estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia Polygenic Risk Score (SZ PRS) was non-significantly associated with a higher number of beads drawn (B= 0.47, 95% CI −0.21 to 1.16, p=0.17); whereas IQ PRS (B=0.51, 95% CI 0.25 to 0.76, p<0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with higher level of psychotic-like experiences (PLE) in controls, including after controlling for IQ (B= −1.7, 95% CI −2.8 to −0.5, p=0.006), but did not relate to delusions in patients.Conclusionsthe JTC reasoning bias in psychosis is not a specific cognitive deficit but is rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to psychotic-like experiences, independent of IQ. The work has potential to inform interventions targeting cognitive biases in early psychosis.

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Precision Colorectal Cancer Screening with Polygenic Risk Score

10.1101/2020.08.19.20177931 ◽

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.

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