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Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

Science China(Life Sciences) 2024年第1期67卷 132-148页

作者： Ming Zhang Xiaoyang Wang Nan Yang Xu Zhu Zequn Lu Yimin Cai Bin Li Ying Zhu Xiangpan Li Yongchang Wei Shaokai Zhang Jianbo Tian Xiaoping Miao department of epidemiology and biostatistics School of Public HealthDepartment of Gastrointestinal OncologyZhongnan Hospital of Wuhan UniversityDepartment of Radiation OncologyRenmin Hospital of Wuhan UniversityTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Research center of Public Health Renmin hospital of Wuhan UniversityWuhan UniversityWuhan 430060China department of cancer epidemiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China department of Radiation Oncology Renmin Hospital of Wuhan UniversityWuhan 430060China department of Gastrointestinal Oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430062China department of epidemiology and biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430073China Jiangsu Collaborative Innovation center for cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly ***,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics *** a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in *** the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in *** subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras ***,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 ***,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC *** summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

关键词： susceptibility genes gene screening models multi-omics GWAS CEBPB long-range promoter-enhancer interactions

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Progranulin:A promising biomarker and therapeutic target for fibrotic diseases

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3312-3326页

作者： Fan Yang Ming-Han Cheng Hai-Feng Pan Jian Gao Pediatric Translational Medicine Institute Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghai 200000China department of Ophthalmology the First Affiliated Hospital of Anhui Medical UniversityHefei 230022China department of epidemiology and biostatistics School of Public HealthAnhui Medical UniversityHefei 230022China Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Hefei 230022China

Progranulin(PGRN),a multifunctional growth factor-like protein expressed by a variety of cell types,serves an important function in the physiologic and pathologic processes of fibrotic diseases,including wound healing and the inflammatory *** was discovered to inhibit proinflammation effect by competing with tumor necrosis factor-alpha(TNF-a)binding to TNF ***,excessive tissue repair in the development of inflammation causes tissue *** investigations have indicated the significance of PGRN in regulating inflammatory ***,multiple studies have shown that PGRN was linked to fibrogenesis,and was considered to monitor the formation of fibrosis in multiple organs,including liver,cardiovascular,lung and *** paper is a comprehensive review summarizing our current knowledge of PGRN,from its discovery to the role in *** is followed by an in-depth look at the characteristics of PGRN,consisting of its structure,basic function and intracellular ***,we will discuss the potential of PGRN in the diagnosis and treatment of fibrosis.

关键词： Progranulin Fibrotic disease Fibrosis Inflammation Biomarker Therapeutic target PGRN/TNFR interaction Signaling pathway

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Development,validation,and transportability of several machine-learned,non-exercise-based VO_(2max)prediction models for older adults

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Journal of Sport and Health Science 2024年第5期13卷 611-620页

作者： Benjamin T.Schumacher Michael J.LaMonte Andrea Z.LaCroix Eleanor M.Simonsick Steven P.Hooker Humberto Parada Jr. John Bellettiere Arun Kumar Herbert Wertheim School of Public Health and Human Longevity Science University of California San DiegoLa JollaCA 92093USA department of epidemiology and Environmental Health School of Public Health and Health ProfessionsUniversity at BuffaloState University of New YorkBuffaloNY 14214USA Translational Gerontology Branch Intramural Research ProgramNational Institute on AgingNational Institutes of HealthBaltimoreMD 21225USA College of Health and Human Services San Diego State UniversitySan DiegoCA 92182USA Division of epidemiology and biostatistics School of Public HealthSan Diego State UniversitySan DiegoCA 92182USA University of California San Diego Moores cancer center La JollaCA 92093USA Computer Science and Engineering and Halicioglu Data Science Institute University of California San DiegoLa JollaCA 92093USA

Background:There exist few maximal oxygen uptake(VO_(2max))non-exercise-based prediction equations,fewer using machine learning(ML),and none specifically for older *** direct measurement of VO_(2max)is infeasible in large epidemiologic cohort studies,we sought to develop,validate,compare,and assess the transportability of several ML VO_(2max)prediction ***:The Baltimore Longitudinal Study of Aging(BLSA)participants with valid VO2_(max)tests were included(n=1080).Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine(SVM)algorithms were trained to predict VO_(2max)*** developed these algorithms for:(a)the overall BLSA,(b)by sex,(c)using all BLSA variables,and(d)variables common in aging ***,we quantified the associations between measured and predicted VO_(2max)and ***:The age was 69.0±10.4 years(mean±SD)and the measured VO_(2max)was 21.6±5.9 mL/kg/*** absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine yielded root mean squared errors of 3.4 mL/kg/min,3.6 mL/kg/min,3.4 mL/kg/min,3.6 mL/kg/min,and 3.5 mL/kg/min,*** quartiles of measured VO_(2max)showed an inverse gradient in mortality *** VO_(2max)variables yielded similar effect estimates but were not robust to ***:Measured VO_(2max)is a strong predictor of *** ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to *** studies should seek to reproduce these results so that VO_(2max),an important vital sign,can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.

关键词： Cardiorespiratory fitness Prediction algorithms epidemiology Mortality

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Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes

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World Journal of Diabetes 2024年第8期15卷 1717-1725页

作者： Jorge M Molina Patricia G Medina Rita A Gomez Julia R Herrera Nancy L Martínez Brenda Hernández Yesenia García department of Endocrinology Children’s Hospital Federico GomezMexico 06720Mexico National Medical center"Siglo XXI" UMAE Hosp EspecialidadesUnidad Invest Med Epidemiol ClinMexican Social Security InstituteMexico 06720Mexico Research Division UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIMexican Institute of Social SecurityMexico 06720Mexico epidemiology Research Unit in Endocrinology and Nutrition Federico Gómez Children’s HospitalMexico 06720Mexico department of Endocrinology Comprehensive Health Unit for Trans PersonsMexico 11340Mexico

BACKGROUND Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus(T2DM),that is,patients who have insulin resistance,obesity,and other cardiovascular risk factors,suggesting that the presence of glutamic acid decarboxylase(anti-GAD65),islet antigen 2(anti-IA2),and zinc transporter 8(anti-Zn8T)antibodies could have deleterious effects on beta cell function,causing failure and earlier requirement for insulin *** To evaluate anti-GAD65,anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of *** This was a case–control study in patients with clinically diagnosed with T2DM(68 cases and 64 controls with and without early insulin dependence respectively),male and female,aged 12–18 ***,blood pressure,glucose,insulin,C-peptide,glycated hemoglobin A1c,and lipid profiles were *** was used to measure anti-GAD65,anti-IA2,and anti-Zn8T *** statistics,Pearson'sχ2 test,Student's t test,and logistic regression was performed.P<0.05 was considered statistically *** There were 132 patients(53.8%female),with a mean age was 15.9±1.3 years,and there was a disease evolution time of 4.49±0.88 *** presence of anti-GAD65,anti-IA2,and anti-Zn8T positivity was found in 29.5%,18.2%,and 15.9%,*** the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity:anti-GAD65 odds ratio(OR):2.42(1.112–5.303,P=0.026);anti-IA2:OR:1.55(0.859–2.818,P=0.105);and anti-Zn8T:OR:7.32(2.039–26.279,P=0.002).CONCLUSION Anti-GAD65 positivity was high in our ***-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype,leading to an increased risk of early insulin dependence.

关键词： Diabetes Obesity Adolescents Autoimmunity Beta cell Insulin requirements

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No association between phosphatase and tensin homolog genetic polymorphisms and colon cancer

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World Journal of Gastroenterology 2009年第30期15卷 3771-3775页

作者： Lynette S Phillips Cheryl L Thompson Alona Merkulova Sarah J Plummer Thomas C Tucker Graham case Li Li department of epidemiology and biostatistics and case comprehensive cancer center Case Western Reserve University Cleveland OH 44106-7136 United States departments of Family Medicine and epidemiology and biostatistics Case Center for Transdisciplinary Research on Energetics and Cancer Case Comprehensive Cancer Center Case Western Reserve University Cleveland OH 44106-7136m United States department of cancer Biology Cleveland Clinic Foundation Cleveland OH 44195-0001 United States Graham casey Department of Preventive Medicine University of Southern California Los Angeles CA 90033-1006 United States assisted with patient referrals recruitment and reviewed the manuscript coordinated the lab work and reviewed the manuscript Li L led the study design data collection and assisted with the manuscript preparation

AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homolog (PTEN) tumor suppressor gene and risk of colon cancer. METHODS: We utilized a population-based casecontrol study of incident colon cancer individuals (n= 421) and controls (n = 483) aged ≥ 30 years to conduct a comprehensive tagSNP association analysis of the PTEN gene. RESULTS: None of the PTEN SNPs were statistically significantly associated with colon cancer when controlled for age, gender, and race, or when additionally adjusted for other known risk factors (P > 0.05). Haplotype analyses similarly showed no association between the PTEN gene and colon cancer. CONCLUSION: Our study does not support PTEN as a colon cancer susceptibility gene.

关键词： Colon cancer Phosphatase and tensinhomolog Candidate gene Genetic polymorphisms Single nucleotide polymorphism association

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SeqSQC: A Bioconductor Package for Evaluating the Sample Quality of Next-generation Sequencing Data

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Genomics, Proteomics & Bioinformatics 2019年第2期17卷 211-218页

作者： Qian Liu Qiang Hu Song Yao Marilyn L. Kwan Janise M. Roh Hua Zhao Christine B. Ambrosone Lawrence H. Kushi Song Liu Qianqian Zhu department of biostatistics University at Buffalo SUNY Buffalo NY14260 USA department of biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center Buffalo NY14263 USA department of cancer Prevention and Control Roswell Park Comprehensive Cancer Center Buffalo NY14263 USA Division of Research Kaiser Permanente Northern California Oakland CA94612 USA department of epidemiology The University of Texas MD Anderson Cancer Center Houston TX77030 USA

As next-generation sequencing (NGS) technology has become widely used to identify genetic causal variants for various diseases and traits,a number of packages for checking NGS data quality have sprung up in public domains. In addition to the quality of sequencing data,sample quality issues,such as gender mismatch,abnormal inbreeding coefficient,cryptic relatedness,and population outliers,can also have fundamental impact on downstream analysis. However,there is a lack of tools specialized in identifying problematic samples from NGS data,often due to the limitation of sample size and variant counts. We developed SeqSQC,a Bioconductor package,to automate and accelerate sample cleaning in NGS data of any scale. SeqSQC is designed for efficient data storage and access,and equipped with interactive plots for intuitive data visualization to expedite the identification of problematic samples. SeqSQC is available at http://bioconductor. org/packages/SeqSQC.

关键词： Next-generation sequencing Quality assessment 1000 Genomes Project Whole-exome sequencing Bioconductor package

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No association between cyclooxygenase-2 and uridine diphosphate glucuronosyltransferase 1A6 genetic polymorphisms and colon cancer risk

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World Journal of Gastroenterology 2009年第18期15卷 2240-2244页

作者： Cheryl L Thompson Sarah J Plummer Alona Merkulova Iona Cheng Thomas C Tucker Graham casey Li Li departments of Family Medicine and epidemiology and biostatistics Case Centerfor Transdisciplinary Research on Energetics and CancerCase Comprehensive Cancer Center Case Western Reserve University. Cleveland OH 44106-7136 United States department of Preventive Medicine University of Southern California Los Angeles CA90033-1006 United States department of cancer Biology Cleveland Clinic Foundation Cleveland OH 44195-0001 United States department of epidemiology and biostatisticsand Institute for Human Genetics University of California SanFrancisco San Francisco CA 94143-0644 United States Markey cancer center University of Kentucky Lexington KY 40504-3381 United States

AIM：To investigate the association of variations in the cyclooxygenase-2 （COX2） and uridine diphosphate glucuronosyltransferase 1A6 （UGTIA6） genes and non-steroidal anti-inflammatory drugs （NSAIDs） use with risk of colon ***： NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGTIA6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms （SNPs） in the COX2 and UGTIA6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population ***： No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk （P 〉 0.05）,and we did not observe that these variants modify the protective effect of NSAIDs （P 〉 0.05）. We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon ***： Our study does not support a role of COX2 and UGTIA6 genetic variations in the development of colon cancer.

关键词： Uridine diphosphate glucuronosyltransferase 1A6 Cyclooxygenase-2 Non-steroidal anti-inflammatorydrugs Colon cancer Genetic association studies Singlenucleotide polymorphisms

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Survival in men older than 75 years with low- and intermediate-grade prostate cancer managed with watchful waiting with active surveillance

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Family Medicine and Community Health 2015年第3期3卷 25-36页

作者： Tzuyung D.Kou Siran M.Koroukian Pingfu Fu Derek Raghavan Gregory S.Cooper Li Li department of epidemiology and biostatistics Case Western Reserve University School of MedicineClevelandOHUSA case comprehensive cancer center Case Western Reserve University School of MedicineClevelandOHUSA Levine cancer Institute Carolinas Healthcare SystemCharlotteNCUSA department of Family Medicine-Research Division Case Western Reserve University School of MedicineClevelandOHUSA

Objective:Recent studies have reported the underuse of active surveillance or watchful wait-ing for low-risk prostate cancer in the United *** study examined prostate cancer-specific and all-cause death in elderly patients older than 75 years with low-risk tumors managed with active treatment versus watchful waiting with active surveillance(WWAS).Methods:We performed survival analysis in a cohort of 18,599 men with low-risk tumors(early and localized tumors)who were 75 years or older at the time of prostate cancer diagnosis in the linked Surveillance,epidemiology,and End Results(SEER)-Medicare database(from 1992 to 1998)and who were followed up through December *** was defined as having an-nual screening for prostate-specific antigen and/or digital rectal examination during the follow-up *** risks of prostate cancer-specific and all-cause death were compared by Cox regression *** propensity score matching technique was used to address potential selection ***:In patients with well-differentiated(Gleason score 2-4)and localized disease,those managed with WWAS without delayed treatment had higher risk of all-cause death(hazard ratio 1.20,95%confidence interval 1.13-1.28)but a substantially lower risk of prostate cancer-specific death(hazard ratio 0.62,confidence interval 0.51-0.75)than patients undergoing active *** managed with WWAS with delayed treatment had comparable mortality ***-tivity analyses based on propensity score matching yielded similar ***:In men older than 75 years with well-differentiated and localized prostate cancer,WWAS without delayed treatment had a lower risk of prostate cancer-specific death and compa-rable all-cause death as compared with active *** patients in whom treatment was delayed had comparable mortality *** results support WWAS as an initial management option for older men with well-differentiated and localized prostate cancer.

关键词： epidemiology watchful waiting prostate cancer

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Efficacy and safety of bamlanivimab in patients with COVID-19:A systematic review and meta-analysis

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World Journal of Virology 2024年第1期13卷 120-132页

作者： Behnam Amani Lida Khodavirdilou Kourosh Rajabkhah Vida Kardan Moghaddam Arash Akbarzadeh Bahman Amani department of Health Management and Economics School of Public HealthTehran University of Medical SciencesTehran ***Iran department of Pharmaceutical Sciences Jerry H.Hodge School of PharmacyTexas Tech University Health Sciences CenterAmarilloTX 79106United States Deputy of Research and Technology Tehran University of Medical SciencesTehran ***Iran School of Medicine and Dentistry Griffith UniversityQueenslandBrisbane 4222Australia department of epidemiology and biostatistics School of Public HealthTehran University of Medical SciencesTehran ***Iran

BACKGROUND Monoclonal antibodies(mAbs)have shown clinical benefits against coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Several studies have reported the use of bamlanivimab as a promising treatment option for *** To synthesize the latest evidence for the efficacy and safety of bamlanivimab alone in the treatment of adult patients with *** A literature search was conducted in PubMed,Cochrane Library,Web of Science,medRxiv,and Google Scholar using“SARS-CoV-2”,“COVID-19”,“LY-CoV555”,and“Bamlanivimab”keywords up to January 25,*** quality of included studies was assessed using the Cochrane bias *** comprehensive Meta-Analysis software version 3.0 was used to analyze the *** A total of 30 studies involving 47368 patients were included.A significant difference was observed between the bamlanivimab and standard of care/placebo groups in terms of mortality rate[risk ratio(RR)=50,95%confidence interval(CI):0.36-0.70],hospitalization rate(RR=0.51;95%CI:0.39-0.68),and emergency department(ED)visits(RR=0.69;95%CI:0.47-0.99);while the two groups exhibited no significant difference in terms of intensive care unit(ICU)admission(P>0.05).Compared to other mAbs,bamlanivimab was associated with a higher rate of hospitalization(RR=1.44;95%CI:1.07-1.94).However,no significant difference was detected between the bamlanivimab and other mAbs groups in terms of mortality rate,ICU admission,and ED(P>0.05).The incidence of any adverse events was similar between the bamlanivimab and control groups(P>0.05).CONCLUSION Although the results suggest the efficacy and safety of bamlanivimab in COVID-19 patients,further research is required to confirm the efficacy of this drug for the current circulating SARS-CoV-2 variants.

关键词： SARS-CoV-2 COVID-19 Bamlanivimab Monoclonal antibody Meta-analysis

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Novel strategy for disease risk prediction incorporating predicted gene expression and DNA methylation data:a multi-phased study of prostate cancer

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cancer Communications 2021年第12期41卷 1387-1397页

作者： Chong Wu Jingjing Zhu Austin King Xiaoran Tong Qing Lu Jong Y.Park Liang Wang Guimin Gao Hong-Wen Deng Yaohua Yang Karen E.Knudsen Timothy R.Rebbeck Jirong Long Wei Zheng Wei Pan David V.Conti Christopher A Haiman Lang Wu department of Statistics Florida State UniversityTallahasseeFL 32304USA cancer epidemiology Division Population Sciences in the Pacific ProgramUniversity of Hawaii Cancer CenterUniversity of Hawaii at ManoaHonoluluHI 96813USA department of epidemiology and biostatistics Michigan State UniversityEast LansingMI 48824USA department of biostatistics University of FloridaGainesvilleFL 32603USA department of cancer epidemiology H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612USA department of Tumor Biology H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612USA department of Public Health Sciences University of ChicagoChicagoIL 60637USA center of Bioinformatics and Genomics Department of Global Biostatistics and Data ScienceTulane UniversityNew OrleansLA 70112USA Division of epidemiology Department of MedicineVanderbilt Epidemiology CenterVanderbilt-Ingram Cancer CenterVanderbilt University Medical CenterNashvilleTN 37203USA department of cancer Biology Sidney Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaPA 19107USA department of Medical Oncology Dana-Farber Cancer InstituteBostonMA 02215USA department of epidemiology Harvard TH Chan School of Public HealthBostonMA 02115USA Division of biostatistics University of MinnesotaMinneapolisMN 55455USA department of Preventive Medicine Keck School of MedicineUniversity of Southern California/Norris Comprehensive Cancer CenterLos AngelesCA 90033USA

Background:DNA methylation and gene expression are known to play important roles in the etiology of human diseases such as prostate cancer(PCa).However,it has not yet been possible to incorporate information of DNA methylation and gene expression into polygenic risk scores(PRSs).Here,we aimed to develop and validate an improved PRS for PCa risk by incorporating genetically predicted gene expression and DNA methylation,and other genomic information using an integrative ***:Using data from the PRACTICAL consortium,we derived multiple sets of genetic scores,including those based on available single-nucleotide polymorphisms through widely used methods of pruning and thresholding,LDpred,LDpred-funt,AnnoPred,and EBPRS,as well as PRS constructed using the genetically predicted gene expression and DNA methylation through a revised pruning and thresholding *** the tuning step,using the UK Biobank data(1458 prevalent cases and 1467 controls),we selected PRSs with the best *** an independent set of data from the UK Biobank,we developed an integrative PRS combining information from individual ***,in the testing step,we tested the performance of the integrative PRS in another independent set of UK Biobank data of incident cases and ***:Our constructed PRS had improved performance(C statistics:76.1%)over PRSs constructed by individual benchmark methods(from 69.6%to 74.7%).Furthermore,our new PRS had much higher risk assessment power than family *** overall net reclassification improvement was 69.0%by adding PRS to the baseline model compared with 12.5%by adding family ***:We developed and validated a new PRS which may improve the utility in predicting the risk of developing *** innovative method can also be applied to other human diseases to improve risk prediction across multiple outcomes.

关键词： risk prediction polygenic risk scores predicted gene expression predicted DNA methylation integrative models prostate cancer

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