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

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; Gudmundur Geirsson; Folkert W Asselbergs; Unnur Thorsteinsdottir; Thorunn Rafnar; Gudmar Thorleifsson; Kari Stefansson

doi:10.1038/s41467-018-06920-9

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

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 JonssonRosa B Barkardottir, Rafn Hilmarsson, Gudmundur Geirsson, Folkert W Asselbergs, Unnur Thorsteinsdottir, Thorunn Rafnar, Gudmar Thorleifsson, Kari Stefansson

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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 _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.

Original language	English
Article number	4568
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-06920-9
Publication status	Published - 8 Nov 2018

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Gudmundsson, J., Sigurdsson, J. K., Stefansdottir, L., Agnarsson, B. A., Isaksson, H. J., Stefansson, O. A., Gudjonsson, S. A., Gudbjartsson, D. F., Masson, G., Frigge, M. L., Stacey, S. N., Sulem, P., Halldorsson, G. H., Tragante, V., Holm, H., Eyjolfsson, G. I., Sigurdardottir, O., Olafsson, I., Jonsson, T., ... Stefansson, K. (2018). Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA. Nature Communications, 9(1), Article 4568. https://doi.org/10.1038/s41467-018-06920-9

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

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 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.",

author = "Julius Gudmundsson and Sigurdsson, \{Jon K\} and Lilja Stefansdottir and Agnarsson, \{Bjarni A\} and Isaksson, \{Helgi J\} and Stefansson, \{Olafur A\} and Gudjonsson, \{Sigurjon A\} and Gudbjartsson, \{Daniel F\} and Gisli Masson and Frigge, \{Michael L\} and Stacey, \{Simon N\} and Patrick Sulem and Halldorsson, \{Gisli H\} and Vinicius Tragante and Hilma Holm and Eyjolfsson, \{Gudmundur I\} and Olof Sigurdardottir and Isleifur Olafsson and Thorvaldur Jonsson and Eirikur Jonsson and Barkardottir, \{Rosa B\} and Rafn Hilmarsson and Gudmundur Geirsson and Asselbergs, \{Folkert W\} and Unnur Thorsteinsdottir and Thorunn Rafnar and Gudmar Thorleifsson and Kari Stefansson",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s).",

year = "2018",

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doi = "10.1038/s41467-018-06920-9",

language = "English",

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Gudmundsson, J, Sigurdsson, JK, Stefansdottir, L, Agnarsson, BA, Isaksson, HJ, Stefansson, OA, Gudjonsson, SA, Gudbjartsson, DF, Masson, G, Frigge, ML, Stacey, SN, Sulem, P, Halldorsson, GH, Tragante, V, Holm, H, Eyjolfsson, GI, Sigurdardottir, O, Olafsson, I, Jonsson, T, Jonsson, E, Barkardottir, RB, Hilmarsson, R, Geirsson, G, Asselbergs, FW, Thorsteinsdottir, U, Rafnar, T, Thorleifsson, G & Stefansson, K 2018, 'Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA', Nature Communications, vol. 9, no. 1, 4568. https://doi.org/10.1038/s41467-018-06920-9

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 - Geirsson, Gudmundur

AU - Asselbergs, Folkert W

AU - Thorsteinsdottir, Unnur

AU - Rafnar, Thorunn

AU - Thorleifsson, Gudmar

AU - Stefansson, Kari

PY - 2018/11/8

Y1 - 2018/11/8

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.

U2 - 10.1038/s41467-018-06920-9

DO - 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 -

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

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