A5087681848- Genetic Associations and Epidemiology
- Prostate Cancer Treatment and Research
- Prostate Cancer Diagnosis and Treatment
- Molecular Biology Techniques and Applications
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Sex and Gender in Healthcare
- Glutathione Transferases and Polymorphisms
- Nutrition, Genetics, and Disease
- Renal cell carcinoma treatment
- Plant Micronutrient Interactions and Effects
- Bioenergy crop production and management
- IL-33, ST2, and ILC Pathways
- Asthma and respiratory diseases
- Crop Yield and Soil Fertility
- Trace Elements in Health
- Genomic variations and chromosomal abnormalities
- Iron Metabolism and Disorders
- Hormonal and reproductive studies
- Genomics and Rare Diseases
University of California, San Francisco
2015-2023
Xiamen University
2023
Dana-Farber Cancer Institute
2023
Eli and Edythe Broad Foundation
2023
Broad Institute
2023
Brigham and Women's Hospital
2023
Harvard University
2023
University of Southern California
2023
National Institutes of Health
2023
National Cancer Institute
2023
Deciphering the shared genetic basis of distinct cancers has potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) comprehensive evaluations heritability pleiotropy across 18 cancer types in two large, population-based cohorts: UK Biobank (408,786 European ancestry individuals; 48,961 cases) Kaiser Permanente Genetic Epidemiology Research on Adult Health Aging cohorts (66,526 16,001...
A genome-wide association study (GWAS) of prostate cancer in Kaiser Permanente health plan members (7,783 cases, 38,595 controls; 80.3% non-Hispanic white, 4.9% African-American, 7.0% East Asian, and 7.8% Latino) revealed a new independent risk indel rs4646284 at the previously identified locus 6q25.3 that replicated PEGASUS (N = 7,539) Multiethnic Cohort 4,679) with an overall P 1.0 × 10(-19) (OR, 1.18). Across locus, exhibited strongest expression SLC22A1 (P 1.3 10(-23)) SLC22A3 3.2...
Abstract Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa—such as genetics—can impact PSA. Here we present findings from a genome-wide association study (GWAS) PSA in 28,503 Kaiser Permanente whites 17,428 men replication cohorts. We detect 40 significant ( P <5 × 10 −8 ) single-nucleotide polymorphisms (SNPs): 19 novel, 15 previously identified (14 which were also PCa-associated), 6 PCa only....
Abstract Genome-wide association study–identified prostate cancer risk variants explain only a relatively small fraction of its familial relative risk, and the genes responsible for many these identified associations remain unknown. To discover novel genetic loci possible causal at previously loci, we performed transcriptome-wide study in 79,194 cases 61,112 controls European ancestry. Using data from Genotype-Tissue Expression Project, established models to predict gene expression across...
Abstract Here we train cis -regulatory models of prostate tissue gene expression and impute transcriptome-wide for 233,955 European ancestry men (14,616 cancer (PrCa) cases, 219,339 controls) from two large cohorts. Among 12,014 genes evaluated in the UK Biobank, identify 38 associated with PrCa, many replicating Kaiser Permanente RPGEH. We report association elevated TMPRSS2 increased PrCa risk (independent a previously-reported variant) tumoral : ERG fusion-oncogene The Cancer Genome...
Risk factors that contribute to inter-individual differences in the age-of-onset of allergic diseases are poorly understood. The aim this study was identify genetic risk variants associated with age at which symptoms disease first develop, considering information from asthma, hay fever and eczema. Self-reported available for 117,130 genotyped individuals European ancestry UK Biobank study. For each individual, we identified earliest and/or eczema diagnosed performed a genome-wide association...
Abstract Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in cancer susceptibility. Investigation of the shared genetic basis these phenotypes UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that genetically correlated with reduced forced expiratory volume one second (FEV 1 : r g = 0.098, p 2.3 × 10 −8 ) ratio FEV vital capacity /FVC: 0.137, 2.0 −12 ). Mendelian randomization analyses...
Abstract Background Cell-free DNA’s (cfDNA) use as a biomarker in cancer is challenging due to genetic heterogeneity of malignancies and rarity tumor-derived molecules. Here we describe demonstrate novel machine-learning guided panel design strategy for improving the detection tumor variants cfDNA. Using this approach, first generated model classify score candidate inclusion on prostate targeted sequencing panel. We then used screen from patients with localized disease both silico hybrid...
ABSTRACT Genetic factors that influence etiologic mechanisms shared across cancers could affect the risk of multiple cancer types. We investigated polygenic score (PRS)-specific pleiotropy 17 in two large population-based cohorts. The study population included European ancestry individuals from Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) UK Biobank (48,969 359,802 controls). selected known independent variants published GWAS to construct a PRS for...
Abstract Deciphering the shared genetic basis of distinct cancers has potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. However, no studies have investigated pan-cancer pleiotropy within single, well-defined populations unselected for phenotype. We undertook novel genome-wide association (GWAS) comprehensive evaluations heritability across 18 cancer types in two large, population-based cohorts: UK Biobank (413,870 European ancestry...
BACKGROUND Benign tissue from a tumor-containing organ is commonly the only available source for obtaining patient's unmutated genome use in cancer research. While it critical to identify histologically normal that independent of tumor lineage, few additional considerations are applied choice this material such measurements. METHODS Normal formalin-fixed, paraffin-embedded seminal vesicle, and urethral tissues, addition whole blood, were collected 31 prostate patients having undergone...
In situ degradability and gas production (GP) parameters of sweet sorghum bagasse silages compared with maize silage were determined in mini silos order to compare the nutritional value ensiled its silage.Experimental treatments 1) (MS) as control, 2) (SS) 3) (BS) both supplemented urea or molasses (10 50 g/kg dry matter (DM) basis, respectively).Triplicate samples prepared for each treatment laboratory 90 days.The DM crude protein (CP) fresh 90-d forages measured using three none lactating...
ABSTRACT The potential association between rare germline genetic variants and prostate cancer (PrCa) susceptibility has been understudied due to challenges with assessing variation. Furthermore, although common risk for PrCa have shown limited individual effect sizes, their cumulative may be of similar magnitude as high penetrance mutations. To identify associated susceptibility, better characterize the mechanisms disease variants, we analyzed large population-based cohorts, custom...
Abstract Background Cell-free DNA’s (cfDNA) use as a biomarker in cancer is challenging due to genetic heterogeneity of malignancies and rarity tumor-derived molecules. Here we describe demonstrate novel machine-learning guided panel design strategy for improving the detection tumor variants cfDNA. Using this approach, first generated model classify score candidate inclusion on prostate targeted sequencing panel. We then used screen from patients with localized disease both silico hybrid...
ABSTRACT Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in cancer susceptibility. Investigation of the shared genetic basis these phenotypes UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that genetically correlated with reduced forced expiratory volume one second (FEV 1 : r g =0.098, p=2.3×10 −8 ) ratio FEV vital capacity /FVC: =0.137, p=2.0×10 −12 ). Mendelian randomization analyses...
<div>Abstract<p>Genome-wide association study–identified prostate cancer risk variants explain only a relatively small fraction of its familial relative risk, and the genes responsible for many these identified associations remain unknown. To discover novel genetic loci possible causal at previously loci, we performed transcriptome-wide study in 79,194 cases 61,112 controls European ancestry. Using data from Genotype-Tissue Expression Project, established models to predict gene...
<p>Supplementary file including three sup figures and 11 tables, Supplementary Note consortia PIs, Funding Acknowledgements, references. Figure 1. Model external performance using data from the Mayo Clinic study by internal (R2) of models built GTEx for (A) prostate tissue models, (B) cross models. 2. TCGA Supplemental 3. Validation knockdown in PC-3, DU-145, (C) LNCaP cells. Table Primer sequences siRNA examined protein-coding genes long non-coding RNAs 4. Internal cross-tissue gene...
<p>Supplementary file including three sup figures and 11 tables, Supplementary Note consortia PIs, Funding Acknowledgements, references. Figure 1. Model external performance using data from the Mayo Clinic study by internal (R2) of models built GTEx for (A) prostate tissue models, (B) cross models. 2. TCGA Supplemental 3. Validation knockdown in PC-3, DU-145, (C) LNCaP cells. Table Primer sequences siRNA examined protein-coding genes long non-coding RNAs 4. Internal cross-tissue gene...
<div>Abstract<p>Genome-wide association study–identified prostate cancer risk variants explain only a relatively small fraction of its familial relative risk, and the genes responsible for many these identified associations remain unknown. To discover novel genetic loci possible causal at previously loci, we performed transcriptome-wide study in 79,194 cases 61,112 controls European ancestry. Using data from Genotype-Tissue Expression Project, established models to predict gene...
<div>Abstract<p>To identify rare variants associated with prostate cancer susceptibility and better characterize the mechanisms cumulative disease risk common variants, we conducted an integrated study of genetic etiology in two cohorts using custom genotyping microarrays, large imputation reference panels, functional annotation approaches. Specifically, 11,984 men (6,196 cases 5,788 controls) European ancestry from Northern California Kaiser Permanente were genotyped...
<div>Abstract<p>To identify rare variants associated with prostate cancer susceptibility and better characterize the mechanisms cumulative disease risk common variants, we conducted an integrated study of genetic etiology in two cohorts using custom genotyping microarrays, large imputation reference panels, functional annotation approaches. Specifically, 11,984 men (6,196 cases 5,788 controls) European ancestry from Northern California Kaiser Permanente were genotyped...