Human genetic approaches to lower urinary tract phenotypes

降低尿路表型的人类遗传学方法

基本信息

批准号：
10487492
负责人：
ALI G GHARAVI
金额：
$ 23.36万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-24 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10487492
关键词：
16S ribosomal RNA sequencing 16p11.2 Address Animal Model BMP5 gene Benign Biological Assay Childhood Chronic Kidney Failure Cohort Studies Collaborations Complex Computerized Medical Record Copy Number Polymorphism Data Diagnostic Disease Dysuria Effectiveness Electronic Health Record Electronic Medical Records and Genomics Network Ensure Event Functional disorder Funding Genes Genetic Genetic Diseases Genetic Predisposition to Disease Genomics Homeostasis Human Genetics Investigation Literature Longterm Follow-up Lower urinary tract Measurement Metabolic Morbidity - disease rate National Human Genome Research Institute National Institute of Diabetes and Digestive and Kidney Diseases Obstruction Outcome Pathogenesis Pathway interactions Patients Pelvic floor structure Phenotype Population Ptosis Questionnaires Research Risk Risk Factors Role Sampling Shapes Signal Transduction Single Nucleotide Polymorphism Symptoms Technology Urinary Incontinence Urinary Microbiome Urinary tract Urinary tract infection Urine Urology Urothelium Variant Vesico-Ureteral Reflux Visit WNT5A gene Work biobank clinical care clinical diagnosis clinical phenotype cohort comorbidity cost diagnostic value exome exome sequencing experience follow-up genetic approach genetic testing genetic variant genome sequencing genome wide association study genomic data genomic locus improved insight lower urinary tract symptoms malformation microbial community microbial genomics microbiome microbiota microbiota profiles novel patient subsets phenome proband rare variant response to injury sex trait urinary urologic

项目摘要

PROJECT 1: PROJECT SUMMARY/ABSTRACT Genomic technologies such as exome sequencing and GWAS have not been systematically applied for most benign urological phenotypes prior to our work at the Columbia O’Brien Urology Research Center. We have already successfully applied genome-wide association study (GWAS) and rare copy-number variant analysis to identify novel genes and loci associated with vesicoureteral reflux (VUR). Here we propose to perform exome sequence of VUR patients to identify diagnostic rare single nucleotide variants and perform an exploratory VUR whole exome association study. In collaboration with the Microbial Genomics Biomedical Core we will conduct 16S rRNA sequencing from urine samples of a set of these patients, with both VUR and urinary tract infections (UTI) to generate urinary microbiota profiles. We will then and analyze microbiota profile associations with phenotypic variants and outcomes and with rare genetic variants, and perform a microbiota-common variant genome-wide association study (mGWAS). To extend these genomic studies to other important benign urology phenotypes we will perform a GWAS of common lower urinary tract symptoms (LUTS) phenotypes, followed by phenome-wide association study to uncover risk factors and comorbidities with common genetic etiology. Our proposed studies will leverage existing data and biospecimens from four NIDDK-funded national cohorts, the RIVUR (UTI with VUR), CUTIE (UTI without VUR), CKiD (pediatric chronic kidney disease, including reflux VUR) and LURN (LUTS) study cohorts; as well as two large population cohorts that combine electronic medical records and genomics, from the UK Biobank and the NHGRI-funded eMERGE network. The proposed studies will provide new insight into the pathogenesis of disorders of high relevance to benign urology and also facilitate introduction of genetic testing into the practice of Urology.