TY - JOUR
T1 - Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA
AU - Gudmundsson, Julius
AU - Sigurdsson, Jon K.
AU - Stefansdottir, Lilja
AU - Agnarsson, Bjarni A.
AU - Isaksson, Helgi J.
AU - Stefansson, Olafur A.
AU - Gudjonsson, Sigurjon A.
AU - Gudbjartsson, Daniel F.
AU - Masson, Gisli
AU - Frigge, Michael L.
AU - Stacey, Simon N.
AU - Sulem, Patrick
AU - Halldorsson, Gisli H.
AU - Tragante, Vinicius
AU - Holm, Hilma
AU - Eyjolfsson, Gudmundur I.
AU - Sigurdardottir, Olof
AU - Olafsson, Isleifur
AU - Jonsson, Thorvaldur
AU - Jonsson, Eirikur
AU - Barkardottir, Rosa B.
AU - Hilmarsson, Rafn
AU - Asselbergs, Folkert W.
AU - Geirsson, Gudmundur
AU - Thorsteinsdottir, Unnur
AU - Rafnar, Thorunn
AU - Thorleifsson, Gudmar
AU - Stefansson, Kari
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85056260448&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30410027
U2 - https://doi.org/10.1038/s41467-018-06920-9
DO - https://doi.org/10.1038/s41467-018-06920-9
M3 - Article
C2 - 30410027
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4568
ER -