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Susceptibility Genes for Erectile Dysfunction

勃起功能障碍的易感基因

基本信息

批准号：
9107190
负责人：
James Hotaling
金额：
$ 25.2万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-15 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9107190
关键词：
Affect African Age of Onset Algorithms Area Asians Atherosclerosis Bioinformatics Candidate Disease Gene Caring Categories Classification Clinic Visits Clinical Collaborations Complex Computerized Medical Record Copy Number Polymorphism Custom DNA Data Diabetes Mellitus Diabetic Nephropathy Diabetic Retinopathy Disease Disease Management Drug Targeting Electronic Health Record Environment Epidemiologic Studies Epidemiology Erectile dysfunction Ethnic group Event Expenditure Future Genes Genetic Genetic Markers Genome Genomics Genotype Health Healthcare Healthcare Systems Heritability Hispanics Implant Individual Injection of therapeutic agent Insulin-Dependent Diabetes Mellitus Intervention Maps Measures Meta-Analysis Modeling Molecular Non-Insulin-Dependent Diabetes Mellitus Nucleotides Operative Surgical Procedures Pathogenesis Patients Penile Prosthesis Pharmaceutical Preparations Pharmacy facility Phenotype Population Prevention Preventive Intervention Questionnaires Records Registries Research Risk Severities Sildenafil citrate Staging Stratification Surveys Susceptibility Gene Testing Time Twin Multiple Birth United States Validation Variant Vietnam Wisconsin Work base biomarker development biomarker discovery case control clinical care clinically relevant cohort cost cost effective diabetic diabetic patient early onset genetic approach genetic information genetic variant genome wide association study high risk high risk men improved inhibitor/antagonist innovation men novel phosphoric diester hydrolase programs public health relevance response sildenafil targeted biomarker targeted treatment tool whole genome

项目摘要

DESCRIPTION (provided by applicant): Erectile dysfunction (ED) affects 1 in 5 men in the United States and has annual healthcare expenditures exceeding $4 billion. The treatment paradigm for ED involves a trial-and-error approach, with the costs of repeated clinic visits now exceeding surgical costs. No candidate molecule has shown clinical potential as a marker of high risk or disease stratification to facilitate either targeted therapy or the prevention of ED. Genetic approaches can accelerate such efforts through mechanistic, drug, and biomarker discovery. Unexplained variation in ED risk points toward genetic influences, supported by heritability of 0.32 in the Vietnam Era Twin (VET) Registry. Small studies in selected populations suggest the influence of specific variants on ED risk and on response to the phosphodiesterase type 5 inhibitor (PDE5i) sildenafil citrate. Without replication, these findings cannot drive translational advances in care. We hypothesize that genetic variants are associated with ED pathogenesis and progression/severity. Collaboration within the Kaiser Permanente (KP) Research Program in Genes, Environment and Health (RPGEH), electronic Medical Record and Genomics (eMERGE) Network, and the Multiethnic Study of Atherosclerosis (MESA) will combine innovative phenotyping with existing and imputed genotypes in a cost-effective strategy of proposed genome-wide association studies (GWAS). We will also focus on elucidating the genetic contribution to ED among diabetic men, a high-risk population. Identifying genes and molecular networks associated with ED and clinical measures of severity will substantially advance our understanding of the disease mechanisms of ED.