A5046956664- Genetic Associations and Epidemiology
- Prostate Cancer Treatment and Research
- Cancer Genomics and Diagnostics
- Prostate Cancer Diagnosis and Treatment
- Genetic Mapping and Diversity in Plants and Animals
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Cancer Treatment and Pharmacology
- HER2/EGFR in Cancer Research
- RNA and protein synthesis mechanisms
- Genetic and phenotypic traits in livestock
- Glutathione Transferases and Polymorphisms
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Dementia and Cognitive Impairment Research
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Attention Deficit Hyperactivity Disorder
- Health, Environment, Cognitive Aging
- BRCA gene mutations in cancer
- Glycosylation and Glycoproteins Research
- Single-cell and spatial transcriptomics
- Phytochemical Studies and Bioactivities
- Asthma and respiratory diseases
University of California, Los Angeles
2020-2025
University of California, San Francisco
2014-2024
Pulmonary Fibrosis Foundation
2024
UCLA Health
2020
Henry Ford Health System
2013
University of Southern California
2013
Cancer Prevention Institute of California
2013
Cleveland Clinic
2013
UCSF Helen Diller Family Comprehensive Cancer Center
2012
University of Chicago
2012
Abstract Purpose: Sensory peripheral neuropathy is a common and sometimes debilitating toxicity associated with paclitaxel therapy. This study aims to identify genetic risk factors for the development of this toxicity. Experimental Design: A prospective pharmacogenetic analysis patients primary breast cancer, randomized arm CALGB 40101, was used predictors onset severity sensory neuropathy. genome-wide association in 855 subjects European ancestry conducted findings were replicated...
Multidrug and toxin extrusion 2 (MATE2-K (SLC47A2)), a polyspecific organic cation exporter, facilitates the renal elimination of antidiabetes drug metformin. In this study, we characterized genetic variants MATE2-K, determined their association with metformin response, elucidated impact by means comparative protein structure model. Four nonsynonymous four in MATE2-K basal promoter region were identified from ethnically diverse populations. Two variants—c.485C>T c.1177G>A—were shown to be...
Abstract Common diseases often show sex differences in prevalence, onset, symptomology, treatment, or prognosis. Although studies have been performed to evaluate at specific SNP associations, this work aims comprehensively survey a number of complex heritable and anthropometric traits. Potential genetically encoded we investigated include differential genetic liability thresholds distributions, gene–sex interaction autosomal loci, major contribution the X-chromosome, gene–environment...
Prostate cancer is the most frequently diagnosed and second fatal nonskin among men in United States. African American are two times more likely to develop die of prostate compared with other ancestries. Previous whole genome or exome tumor-sequencing studies have primarily focused on European ancestry. In this study, we sequenced characterized somatic mutations aggressive (Gleason ≥7, stage ≥T2b) tumors from 24 patients. We describe locations prevalence small (up 50 bases length), copy...
The genetic control of gene expression is a core component human physiology. For the past several years, transcriptome-wide association studies have leveraged large datasets linked genotype and RNA sequencing information to create powerful gene-based test that has been used in dozens studies. While numerous discoveries made, populations training data are overwhelmingly European descent, little known about generalizability these models other populations. Here, we for cross-population...
Genetic studies of metabolites have identified thousands variants, many which are associated with downstream metabolic and obesogenic disorders. However, these relied on univariate analyses, reducing power limiting context-specific understanding. Here we aim to provide an integrated perspective the genetic basis by leveraging Finnish Metabolic Syndrome In Men (METSIM) cohort, a unique resource contains measurements, mostly lipids, across distinct time points as well information statin usage....
Abstract Circulating cell-free DNA (cfDNA) in the bloodstream originates from dying cells and is a promising noninvasive biomarker for cell death. Here, we propose an algorithm, CelFiE, to accurately estimate relative abundances of types tissues contributing cfDNA epigenetic sequencing. In contrast previous work, CelFiE accommodates low coverage data, does not require CpG site curation, estimates contributions multiple unknown that are available external reference data. simulations, known...
One-third of type 2 diabetes patients do not respond to metformin. Genetic variants in metformin transporters have been extensively studied as a likely contributor this high failure rate. Here, we investigate, for the first time, effect genetic transcription factors on pharmacokinetics (PK) and response. Overall, 546 healthy volunteers contributed their genome-wide, pharmacokinetic (235 subjects), HbA1c data (440 patients) analysis. Five specificity protein 1 (SP1), factor that modulates...
Prostate cancer is the most frequent and second lethal in men United States. Innate immunity inflammation may increase risk of prostate cancer. To determine role innate advanced cancer, we investigated association 320 single nucleotide polymorphisms, located 46 genes involved this pathway, with disease using 494 cases 536 controls from Cleveland, Ohio. Taken together, whole pathway was associated (P = 0.02). Two sub-pathways (intracellular antiviral molecules extracellular pattern...
An important step in analyzing genetic association study data is deciding whether to adjust for covariates—those variables ancillary the variants of interest. In particular, when testing novel associations, should statistical model also include known or nongenetic covariates that are predictors trait (e.g., body mass index studying type 2 diabetes)? Yes, if correlated with primary but do not mediate their effects, because they may confound associations. Including them helps control bias and...
Bosentan (Tracleer) is an endothelin receptor antagonist prescribed for the treatment of pulmonary arterial hypertension (PAH). Its use limited by drug-induced liver injury (DILI). To identify genetic markers DILI, association analyses were performed on 56 Caucasian PAH patients receiving bosentan. Twelve functional polymorphisms in five genes (ABCB11, ABCC2, CYP2C9, SLCO1B1, and SLCO1B3) implicated bosentan pharmacokinetics tested associations with alanine aminotransferase (ALT), aspartate...
Abstract Background: Recent work detected for the first time a high-risk prostate cancer mutation, in homeobox B13 (HOXB13) among European-Americans. Methods: We further evaluated this G84E missense mutation (rs138213197) two genetic association studies of cancer: family-based study brothers and case–control more aggressive disease (N = 2,665 total). then calculated overall impact by pooling all published Results: In our studies, was found exclusively men with (carrier frequency 1.48%) or...
Highlights•Meta-analysis with 6,544 mice found 93 quantitative trait loci for fear-related behavior•Quantitative complementation testing identified six genes at loci•Epigenetic analyses implicated excitatory neurons as mediating the genetic effects•Genetic variation occurs preferentially in versus inhibitory neuronal circuitsSummaryKnowing involved traits provides an entry point to understanding biological bases of behavior, but there are very few examples where pathway from locus behavioral...
The gasoline additive MTBE, methyl tert ‐butyl ether, is a widespread and persistent groundwater contaminant. MTBE undergoes rapid mineralization as the sole carbon energy source of bacterial strain PM1, isolated from an enrichment culture compost biofilter material. In this report, we describe results microbial community DNA profiling to assess relative dominance isolate PM1 other strains cultured enrichment. Three polymerase chain reaction (PCR)‐based approaches were evaluated: denaturing...
Abstract Biological, technical, and environmental confounders are ubiquitous in the high-dimensional, high-throughput functional genomic measurements being used to understand cellular biology disease processes, many approaches have been developed estimate correct for unmeasured confounders... High-throughput of molecular phenotypes provide an unprecedented opportunity model processes their impact on disease. These highly structured datasets usually strongly confounded, creating false...
Large-scale cohorts with combined genetic and phenotypic data, coupled methodological advances, have produced increasingly accurate predictors of complex human phenotypes called polygenic risk scores (PRSs). In addition to the potential translational impacts identifying at-risk individuals, PRS are being utilized for a growing list scientific applications, including causal inference, pleiotropy correlation, powerful gene-based mixed-model association tests. Existing approaches rely on...
Our knowledge of the contribution genetic interactions ( epistasis ) to variation in human complex traits remains limited, partly due lack efficient, powerful, and interpretable algorithms detect interactions. Recently proposed approaches for set-based association tests show promise improving power by examining aggregated effects multiple variants. Nevertheless, these methods either do not scale large Biobank data sets or interpretability. We propose QuadKAST, a scalable algorithm focused on...
Background First-generation gene signatures that identify breast cancer patients at risk of recurrence are confined to estrogen-positive cases and driven by genes involved in the cell cycle proliferation. Previously we induced sets stromal prognostic for both estrogen-negative samples. Creating risk-management tools incorporate these signatures, along with existing proliferation-based established clinicopathological measures such as lymph node status tumor size, should better women greatest...