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

• Published in: Nature Communications
• Main Authors: Gudmundsson, Julius, Sigurðsson, Jón K., Stefánsdóttir, Lilja, Agnarsson, Bjarni A., Ísaksson, Helgi J., Stefánsson, Ólafur A., Guðjónsson, Sigurjón Axel, Gudbjartsson, Daniel, Másson, Gísli, Frigge, Michael L., Stacey, Simon N., sulem, patrick, Halldorsson, Gisli, Tragante, Vinicius, Holm, Hilma, Eyjólfsson, Guðmundur I., Sigurðardóttir, Ólöf, Olafsson, Isleifur, Jónsson, Þorvaldur, Jónsson, Eirikur, Barkardottir, Rosa Bjork, Hilmarsson, Rafn, Asselbergs, Folkert W., Geirsson, Guðmundur, Thorsteinsdottir, Unnur, Rafnar, Thorunn, Thorleifsson, Gudmar, Stefansson, Kari
• Other Authors: Faculty of Medicine (UI), Læknadeild (HÍ), Biomedical Center (UI), Lífvísindasetur (HÍ), School of Health Sciences (UI), Heilbrigðisvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Verkfræði- og náttúruvísindasvið (HÍ), Háskóli Íslands (HÍ), University of Iceland (UI)
• Format: Article in Journal/Newspaper
• Language: English
• Published: Springer Science and Business Media LLC 2018
• Subjects: Cancer; Genetics; Krabbamein; Blöðruhálskirtilskrabbamein; Erfðafræði; Rannsóknir; Iceland
• Online Access: https://hdl.handle.net/20.500.11815/1385; https://doi.org/10.1038/s41467-018-06920-9

Publisher's version (útgefin grein) Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 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 g = 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. We thank the individuals that participated in the study and whose contribution made this work possible. This research has been conducted using the UK Biobank Resource under Application Number 24711. Folkert W. Asselbergs is supported by UCL Hospitals NIHR Biomedical Research Centre. We acknowledge the Icelandic Cancer Registry for assistance in the ascertainment of the cancer patients. Peer Reviewed