Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA.

Gudmundsson, Julius; Sigurdsson, Jon K; Stefansdottir, Lilja; Agnarsson, Bjarni A; Isaksson, Helgi J; Stefansson, Olafur A; Gudjonsson, Sigurjon A; Gudbjartsson, Daniel F et al. · Nat Commun · 2018

other · Level V

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Abstract

Benign prostatic hyperplasia and associated lower urinary tract symptoms (BPH/LUTS) are common conditions affecting the majority of elderly males. Here we report the results of a genome-wide association study of symptomatic BPH/LUTS in 20,621 patients and 280,541 controls of European ancestry, from Iceland and the UK. We discovered 23 genome-wide significant variants, located at 14 loci. There is little or no overlap between the BPH/LUTS variants and published prostate cancer risk variants. However, 15 of the variants reported here also associate with serum levels of prostate specific antigen (PSA) (at a Bonferroni corrected P < 0.0022). Furthermore, there is a strong genetic correlation, r<sub>g</sub> = 0.77 (P = 2.6 × 10<sup>-11</sup>), between PSA and BPH/LUTS, and one standard deviation increase in a polygenic risk score (PRS) for BPH/LUTS increases PSA levels by 12.9% (P = 1.6×10<sup>-55</sup>). These results shed a light on the genetic background of BPH/LUTS and its substantial influence on PSA levels.

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