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.

Public Health Relevance

Erectile dysfunction exerts a significant burden on patients and the healthcare system, affecting one in five men and having annual costs in excess of $4 billion. This project matches small differences in DNA to men at highest risk for erectile dysfunction. Our findings have the potential to move ED treatment beyond a trial and error approach, informing clinical care for men with diabetes and others who need complex management.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK104764-01A1
Application #
9107190
Study Section
Special Emphasis Panel (ZRG1-DKUS-G (90)S)
Program Officer
Rasooly, Rebekah S
Project Start
2016-09-15
Project End
2019-05-31
Budget Start
2016-09-15
Budget End
2017-05-31
Support Year
1
Fiscal Year
2016
Total Cost
$231,750
Indirect Cost
$47,666
Name
University of Washington
Department
Urology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Jorgenson, Eric; Matharu, Navneet; Palmer, Melody R et al. (2018) Genetic variation in the SIM1 locus is associated with erectile dysfunction. Proc Natl Acad Sci U S A 115:11018-11023