UUI-GWAS

As noted by NIH GWAS policy, a genome-wide association study is defined as a genetic association study in which the density of genetic markers and the extent of linkage disequilibrium is sufficient to capture a large proportion of the common variation in the human genome in the population under study, and the number of specimens genotyped provides sufficient power to detect variants of modest effect (NIH, 2012).

Genome-wide association studies (GWAS) use research tools and technologies that rapidly and cost-effectively analyze many sites of genetic variation to identify genetic differences among people with specific illnesses, such as diabetes or heart disease, compared to healthy individuals. The purpose of a GWAS is to explore the connection between genetic variation, known as genotype information, and a disease or physical characteristic, known as phenotype information. Genome wide association studies facilitate the identification of genotypes associated with the development or progression of disease without any a priori assumptions about the functional importance of a gene (NIH, 2012).

The study will evaluate the baseline levels of biomarkers in urine of patients with refractory UUI and changes associated with response to therapy which may be indicative of differential effects to the 2 treatments. In addition, the study will characterize the pathophysiologic processes associated with UUI (pre- and post-treatment) and provide valuable information on the prognosis of therapeutic success/failure.

The levels of biomarkers in patients with UUI at baseline and in response to treatment will be compared to those in subjects without lower urinary tract symptoms (control group) over a similar period of time. Additional effort will be undertaken to characterize cell populations present in the urine of enrolled patients.

UUI-GWAS Study Primary Aim:

• To perform a genome-wide association study in a well characterized cohort of post-reproductive women to identify genetic variants that are associated with prevalent urgency urinary incontinence.

We propose to accomplish this by performing a GWAS and a replication study using cases and appropriate controls obtained from the GARNET WHI cohort.

Hypothesis: There are common genetic variants (population frequency > 0.05) that contribute to the risk of developing urgency urinary incontinence; these genetic variants either through direct association or through indirect association (i.e., linkage disequilibrium) predispose women to UUI.

STUDY RESULTS

Richter HE, Whitehead N, Arya L, Ridgeway B, Allen-Brady K, Norton P, Sung V, Shepherd JP, Komesu Y, Gaddis N, Fraser MO, Tan-Kim J, Meikle S, Page GP, Pelvic Floor Disorders Network. Genetic contributions to urgency urinary incontinence in women. The Journal of urology. 2015 Jun; 193(6): 2020-7.

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