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, rg = 0.77 (P = 2.6 × 10-11), 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 = 1.6×10-55). These results shed a light on the genetic background of BPH/LUTS and its substantial influence on PSA levels.
Nature communications. 2018 Nov 08*** epublish ***
Julius Gudmundsson, Jon K Sigurdsson, Lilja Stefansdottir, Bjarni A Agnarsson, Helgi J Isaksson, Olafur A Stefansson, Sigurjon A Gudjonsson, Daniel F Gudbjartsson, Gisli Masson, Michael L Frigge, Simon N Stacey, Patrick Sulem, Gisli H Halldorsson, Vinicius Tragante, Hilma Holm, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Isleifur Olafsson, Thorvaldur Jonsson, Eirikur Jonsson, Rosa B Barkardottir, Rafn Hilmarsson, Folkert W Asselbergs, Gudmundur Geirsson, Unnur Thorsteinsdottir, Thorunn Rafnar, Gudmar Thorleifsson, Kari Stefansson
deCODE genetics/AMGEN, 101, Reykjavik, Iceland. ., deCODE genetics/AMGEN, 101, Reykjavik, Iceland., Landspitali-University Hospital, 101, Reykjavik, Iceland., The Clinical Laboratory in Mjodd, 109, Reykjavik, Iceland., Department of Clinical Biochemistry, Akureyri Hospital, 600, Akureyri, Iceland., Laboratory of Cell Biology, Department of Pathology, Landspitali University Hospital, 101, Reykjavik, Iceland., Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, University of Utrecht, 3584 CX, Utrecht, The Netherlands., deCODE genetics/AMGEN, 101, Reykjavik, Iceland. .