Susceptibility Genes for Erectile Dysfunction

勃起功能障碍的易感基因

• 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
• 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

 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.

 描述（由适用提供）：勃起功能障碍（ED）影响美国5分之一，年度医疗保健支出超过40亿美元。 ED的治疗范式涉及一种试验方法，重复诊所就诊的费用超过了手术费用。没有候选分子显示出临床潜力是高风险或疾病分层的标志，以促进靶向治疗或预防ED。遗传方法可以通过机械，药物和生物标志物发现加速此类工作。 ED风险的无法解释的差异指向遗传影响，在越南时代双胞胎（VET）注册表中为0.32的遗传力支持。选定人群中的小型研究表明，特定变体对ED风险的影响以及对磷酸二酯酶5型抑制剂（PDE5I）的反应。没有复制，这些发现将无法推动转化的护理进步。我们假设遗传变异与ED发病机理和进展/严重程度有关。 Kaiser Permanente（KP）基因，环境与健康（RPGEH），电子医疗和基因组学（EMERGE）网络以及动脉粥样硬化多种族研究（MESA）的合作将结合创新的表型与现有和估算的基因型与拟议策略策略策略相关研究（GWAS）（GWAS）的成本效果。我们还将着重于阐明高风险人群糖尿病男性对ED的遗传贡献。识别与ED相关的基因和分子网络以及严重程度的临床度量将大大提高我们对ED疾病机制的理解。