Abstract
Benign prostatic hyperplasia (BPH) results in a significant public health burden due to the morbidity caused by the disease and many of the available remedies. As much as 70% of men over 70 will develop BPH. Few studies have been conducted to discover the genetic determinants of BPH risk. Understanding the biological basis for this condition may provide necessary insight for development of novel pharmaceutical therapies or risk prediction. We have evaluated SNP-based heritability of BPH in two cohorts and conducted a genome-wide association study (GWAS) of BPH risk using 2,656 cases and 7,763 controls identified from the Electronic Medical Records and Genomics (eMERGE) network. SNP-based heritability estimates suggest that roughly 60% of the phenotypic variation in BPH is accounted for by genetic factors. We used logistic regression to model BPH risk as a function of principal components of ancestry, age, and imputed genotype data, with meta-analysis performed using METAL. The top result was on chromosome 22 in SYN3 at rs2710383 (p-value = 4.6 × 10−7; Odds Ratio = 0.69, 95% confidence interval = 0.55–0.83). Other suggestive signals were near genes GLGC, UNCA13, SORCS1 and between BTBD3 and SPTLC3. We also evaluated genetically-predicted gene expression in prostate tissue. The most significant result was with increasing predicted expression of ETV4 (chr17; p-value = 0.0015). Overexpression of this gene has been associated with poor prognosis in prostate cancer. In conclusion, although there were no genome-wide significant variants identified for BPH susceptibility, we present evidence supporting the heritability of this phenotype, have identified suggestive signals, and evaluated the association between BPH and genetically-predicted gene expression in prostate.
Highlights
Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN, USA
We evaluated genetic heritability of clinically reported Benign prostatic hyperplasia (BPH) and conducted a genome-wide association studies (GWAS) using cases and controls identified from the Electronic Medical Records and Genomic network, and evaluated the contribution of the genetic associations to gene expression in prostate tissue
single nucleotide polymorphism (SNP)-based additive heritability among common variants was assessed in the 5 sites of the Electronic Medical Records and Genomic (eMERGE)-1 network and one of the Geisinger datasets (CoreExome) as they had the largest number of cases assessed on a common genotyping array (Table 1)
Summary
BPH susceptibility, we present evidence supporting the heritability of this phenotype, have identified suggestive signals, and evaluated the association between BPH and genetically-predicted gene expression in prostate. The available surgical remedies can present additional risks and have considerable potential consequences for reproductive and urinary tract health[17,18,19,20,21]. We evaluated genetic heritability of clinically reported BPH and conducted a GWAS using cases and controls identified from the Electronic Medical Records and Genomic (eMERGE) network, and evaluated the contribution of the genetic associations to gene expression in prostate tissue
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