A5035831263- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Prostate Cancer Treatment and Research
- Genomic variations and chromosomal abnormalities
- Prostate Cancer Diagnosis and Treatment
- Health, Environment, Cognitive Aging
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Sleep and Wakefulness Research
- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
- Bipolar Disorder and Treatment
- Genomics and Phylogenetic Studies
- Gene expression and cancer classification
- Genetic Mapping and Diversity in Plants and Animals
- Prenatal Screening and Diagnostics
- Telomeres, Telomerase, and Senescence
- BRCA gene mutations in cancer
- Genetics and Neurodevelopmental Disorders
- Research Data Management Practices
- Adolescent and Pediatric Healthcare
- Hernia repair and management
- Glutathione Transferases and Polymorphisms
- RNA modifications and cancer
- Lipoproteins and Cardiovascular Health
Kaiser Permanente
2023-2025
University of California, San Francisco
2016-2025
W. M. Keck Foundation
2004
Syracuse University
1992
Abstract Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort analyzed relationship to self-reported race/ethnicity. Participants endorsed any 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report cohort is 80.8% white 19.2% minority; 93.8% a single group, while 6.2% two or...
Abstract The Kaiser Permanente (KP) Research Program on Genes, Environment and Health (RPGEH), in collaboration with the University of California—San Francisco, undertook genome-wide genotyping >100,000 subjects that constitute Genetic Epidemiology Adult Aging (GERA) cohort. project, which generated >70 billion genotypes, represents first large-scale use Affymetrix Axiom Genotyping Solution. Because took place over a short 14-month period, creating near-real-time analysis...
Abstract Body mass index (BMI), a proxy measure for obesity, is determined by both environmental (including ethnicity, age, and sex) genetic factors, with > 400 BMI-associated loci identified to date. However, the impact, interplay, underlying biological mechanisms among BMI, environment, genetics, ancestry are not completely understood. To further examine these relationships, we utilized 427,509 calendar year-averaged BMI measurements from 100,418 adults single large multiethnic...
Exome and whole-genome sequencing studies are becoming increasingly common, but little is known about the accuracy of genotype calls made by commonly used platforms. Here we use replicate high-coverage blood saliva DNA samples from four European-American individuals to estimate lower bounds on error rates Complete Genomics Illumina HiSeq whole-exome sequencing. Error for nonreference range 0.1% 0.6%, depending platform depth coverage. Additionally, found (1) no difference in profiles or...
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...
The Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) Genetic Epidemiology Adult Aging (GERA) cohort includes DNA specimens extracted from saliva samples of 110,266 individuals. Because its relationship to aging, telomere length measurement was considered an important biomarker develop these subjects. To assay relative (TL) this large over a short time period, we created novel high throughput robotic system for TL analysis informatics. Samples were run in...
Abstract Elevated intraocular pressure (IOP) is a major risk factor for glaucoma, leading cause of blindness. IOP heritability has been estimated to up 67%, and date only 11 loci have reported, accounting 1.5% variability. Here, we conduct genome-wide association study in 69,756 untreated individuals European, Latino, Asian, African ancestry. Multiple longitudinal measurements were collected through electronic health records and, total, 356,987 included. We identify 47 significant...
The diagnostic yield of exome sequencing (ES) has primarily been evaluated in individuals European ancestry, with less focus on underrepresented minority (URM) and underserved (US) patients. We the ES a cohort predominantly US URM pediatric prenatal patients suspected to have genetic disorder. Eligible had multiple congenital anomalies and/or neurocognitive disabilities one or more structural anomalies, disorders fetal growth, effusions. were prioritized for enrollment underwent at single...
Abstract It has been suggested that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those European ancestry. We examined the association of DY estimated continental/subcontinental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort. Cases ( N = 845) suspected disorders underwent ES for diagnosis. Continental/subcontinental proportions were data. compared distribution positive, negative,...
Short-term adaptation and recovery from have a strong impact on the processing of dynamic stimuli. Adaptive effects neuronal activity been studied most commonly for changes in first-order statistics stimuli such as stepwise increments or decrements stimulus amplitude. However, higher moment statistics, variance amplitude distribution visual stimuli, also can invoke pronounced behavior. We demonstrate here that neurons inferior colliculus (ICC) cat show to auditory differ their modulation...
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....
An efficient approach to characterizing the disease burden of rare genetic variants is impute them into large well-phenotyped cohorts with existing genome-wide genotype data using sequenced referenced panels. The success this hinges on accuracy variant imputation, which remains controversial. For example, a recent study suggested that one cannot adequately HOXB13 G84E mutation associated prostate cancer risk (carrier frequency 0.0034 in European ancestry participants 1000 Genomes Project)....
Newborn screening (NBS) for rare conditions is performed in all 50 states the USA. We have partnered with California Department of Public Health Genetic Disease Laboratory to determine whether sufficient DNA can be extracted from archived dried blood spots (DBS) next-generation sequencing hopes that play a role NBS. optimized extraction and library preparation protocols residual infant DBS over 20 years ago successfully obtained acceptable whole exome genome data. This study using without...
Abstract Central corneal thickness (CCT) is one of the most heritable human traits, with broad-sense heritability estimates ranging between 0.68 to 0.95. Despite high and numerous previous association studies, only 8.5% CCT variance currently explained. Here, we report results a multiethnic meta-analysis available genome-wide studies in which find 98 genomic loci, 41 are novel. Among these 20 were significantly associated keratoconus, ( RAPSN rs3740685) was glaucoma after Bonferroni...
Statin pharmacogenetic implementation guidelines are derived from evidence of primarily Eurocentrically biased study populations. Functional SLCO1B1 variants that rare in these populations have not been equitably investigated and thus missing guidelines. The objective this precision medicine health equity was to determine the clinical validity understudied candidate functional common people with 1,000 Genomes sub-Saharan African superpopulation (1KG-AFR-like) genetic similarity. We conducted...
Abdominal hernias are caused by the protrusion of an organ or tissue through a weakened abdominal wall. Genome-wide association studies (GWAS) have identified 81 genetic susceptibility loci for different hernia subtypes, with 26 associated more than one type; however, additional work is needed to prioritize causal genes at known GWAS loci, identify novel ones, and characterize shared effects across subtypes. We conduct transcriptome-wide study (TWAS) analyses four subtypes (i.e., inguinal,...
Telomere length (TL) may serve as a biologic marker of aging. We examined neighborhood and individual-level socioeconomic status (SES) in relation to TL.The study included 84,996 non-Hispanic white subjects from the Genetic Epidemiology Research on Adult Health Aging (GERA) cohort, part Program Genes, Environment Health. Relative TL (T/S) was log2 transformed improve normality standardized have mean 0 variance 1. Neighborhood SES measured using Deprivation Index (NDI), individual by...