scholarly journals A Deep Learning-based Genome-wide Polygenic Risk Score for Common Diseases Identifies Individuals with Risk

2021 ◽  
Author(s):  
Jiajie Peng ◽  
Jingyi Li ◽  
Ruijiang Han ◽  
Yuxian Wang ◽  
Lu Han ◽  
...  
Keyword(s):  
Deep Learning ◽  
High Risk ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Polygenic Risk ◽  
Common Diseases ◽  
Genome Wide ◽  
Risk Snps ◽  
Health Need

Identifying individuals at high risk in the population is a key public health need. For many common diseases, individual susceptibility may be influenced by genetic variation. Recently, the clinical potential of polygenic risk score (PRS) has attracted widespread attention. However, the performance of traditional methods is limited in fitting capabilities of the linear model and unable to capture the interaction information between single nucleotide polymorphisms (SNPs). To fill this gap, a novel deep-learning-based model named DeepPRS is developed for scoring the risk of common diseases with genome-wide genotype data. Using the UK Biobank dataset, the evaluation shows that DeepPRS performs better than the other two existing state-of-art methods on Alzheimer's disease, inflammatory bowel disease, type 2 diabetes and breast cancer. Since DeepPRS does not only rely on the addictive effect of risk SNPs, DeepPRS has the chance to identify high-risk individuals even with few known risk SNPs.

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 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.

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, genome-wide association, and gene set analyses of cognitive domain deficits in schizophrenia

2018 ◽  
Vol 201 ◽  
pp. 393-399 ◽  
Author(s):  
Soichiro Nakahara ◽  
Sarah Medland ◽  
Jessica A. Turner ◽  
Vince D. Calhoun ◽  
Kelvin O. Lim ◽  
...  
Keyword(s):  
Risk Score ◽  
Genome Wide Association ◽  
Cognitive Domain ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Gene Set ◽  
Genome Wide

Abstract PO-163: Genome-wide polygenic risk score of prostate cancer in African and European ancestry men

2022 ◽  
Author(s):  
Burcu F. Darst ◽  
Ravi K Madduri ◽  
Alexis A. Rodriguez ◽  
Xin Sheng ◽  
Rosalind A. Eeles ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Score ◽  
European Ancestry ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Genome Wide

Individuals with common diseases but with a low polygenic risk score could be prioritized for rare variant screening

2020 ◽  
Author(s):  
Tianyuan Lu ◽  
Sirui Zhou ◽  
Haoyu Wu ◽  
Vincenzo Forgetta ◽  
Celia M. T. Greenwood ◽  
...  
Keyword(s):  
Rare Variant ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Common Diseases

Genome-wide association study (GWAS) of chemotherapy-induced Raynaud's phenomenon (RP) to reveal shared pathways with cardiovascular disease (CVD).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18162-e18162
Author(s):  
Omar El Charif ◽  
Heather E. Wheeler ◽  
Matthew Trendowski ◽  
Eric R Gamazon ◽  
Shirin Ardeshirrouhanifard ◽  
...  
Keyword(s):  
Risk Score ◽  
Cellular Response ◽  
Genome Wide Association Study ◽  
Significant Snps ◽  
Case Control ◽  
Gene Set Enrichment Analysis ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Genome Wide ◽  
Patient Reported

e18162 Background: RP is an adverse drug reaction characterized by reduced blood flow to the extremities causing pain and sensations of cold. Few studies have examined the genetic basis for RP, although family studies suggest a heritable component to primary RP. Methods: Eligible testicular cancer survivors (TCS) were < 55 y at diagnosis, treated with first line cisplatin-based chemotherapy, and completed questionnaires. Genotyping with standard quality control and imputation were performed. A case-control RP phenotype was derived from patient-reported outcomes and associations were computed by logistic regression. GWAS used cumulative bleomycin dose and 10 genetic principal components as covariates. Gene set enrichment analysis (GSEA) utilized genes ranked by the most significant GWAS SNP in/within 20 kilobases. A polygenic risk score for CVD derived from four prior independent GWAS (Khera et al. NEJM 2016) was assessed for association with RP. Results: Of 749 patients (median age 38 y, median time since chemotherapy 5 y), 38% reported RP. Bleomycin dose was the most significant predictor of RP (OR100 mg/m2 = 1.25, p < 0.0001). Number of years smoking also correlated with RP (ORyear = 1.05, p = 0.002). Age and hypertension showed no significant correlation with RP. GSEA revealed several significant pathways (FDR q < 0.1), including “ cellular response to VEGF stimulus” (q = 0.05) and “ cardiac muscle cell action potential” (q = 0.09). We hypothesized that RP may share genetic architecture with CVD. Deriving a polygenic risk score from genome-wide significant SNPs in prior CVD GWAS (n = 4260-22,389), we showed nearly significant case-control differences in CVD polygenic risk score (two-tailed t-test, p = 0.053). RP frequency significantly increased with polygenic risk score quartile (OR = 1.19, p = 0.008). Conclusions: Over one third of TCS report RP, with greater frequency among bleomycin-treated patients and smokers. Implicated genetic pathways include ones established in CVD. Although shared genetic risk between chemotherapy-induced RP and CVD may be possible, further investigation is required. Primary RP has been inconsistently linked with CVD.

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

Performance of polygenic risk scores for cancer prediction in an academic biobank.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1528-1528
Author(s):  
Heena Desai ◽  
Anh Le ◽  
Ryan Hausler ◽  
Shefali Verma ◽  
Anurag Verma ◽  
...  
Keyword(s):  
Risk Score ◽  
Genetic Variants ◽  
Association Studies ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Polygenic Risk ◽  
European Americans ◽  
Genome Wide ◽  
Common Genetic Variants

1528 Background: The discovery of rare genetic variants associated with cancer have a tremendous impact on reducing cancer morbidity and mortality when identified; however, rare variants are found in less than 5% of cancer patients. Genome wide association studies (GWAS) have identified hundreds of common genetic variants significantly associated with a number of cancers, but the clinical utility of individual variants or a polygenic risk score (PRS) derived from multiple variants is still unclear. Methods: We tested the ability of polygenic risk score (PRS) models developed from genome-wide significant variants to differentiate cases versus controls in the Penn Medicine Biobank. Cases for 15 different cancers and cancer-free controls were identified using electronic health record billing codes for 11,524 European American and 5,994 African American individuals from the Penn Medicine Biobank. Results: The discriminatory ability of the 15 PRS models to distinguish their respective cancer cases versus controls ranged from 0.68-0.79 in European Americans and 0.74-0.93 in African Americans. Seven of the 15 cancer PRS trended towards an association with their cancer at a p<0.05 (Table), and PRS for prostate, thyroid and melanoma were significantly associated with their cancers at a bonferroni corrected p<0.003 with OR 1.3-1.6 in European Americans. Conclusions: Our data demonstrate that common variants with significant associations from GWAS studies can distinguish cancer cases versus controls for some cancers in an unselected biobank population. Given the small effects, future studies are needed to determine how best to incorporate PRS with other risk factors in the precision prediction of cancer risk. [Table: see text]

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