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Genome-wide association study identifies novel single nucleotide polymorphisms having age-specific effect on prostate-specific antigen levels

Li, Weiqiang ; Bicak, Mesude ; Sjoberg, Daniel D. ; Vertosick, Emily ; Dahlin, Anders LU ; Melander, Olle LU orcid ; Ulmert, David LU ; Lilja, Hans LU orcid and Klein, Robert J. (2020) In Prostate 80(16). p.1405-1412
Abstract

Background: Testing for prostate-specific antigen (PSA) levels in blood are widely used and associated with prostate cancer risk and outcome. After puberty, PSA levels increase by age and multiple single nucleotide polymorphisms (SNPs) have been found to be associated with PSA levels. However, the relationship between the effects of SNPs and age on PSA remains unknown. Methods: To test for SNP × age interaction, we conducted a genome-wide association study using 2394 men without prostate cancer diagnosis from Malmö, Sweden as a discovery set and 2137 men from the eMERGE study (USA) for validation. Linear regression was used to identify significant interactions between SNP and age (p < 1 × 10−4 for discovery, p <.05 for... (More)

Background: Testing for prostate-specific antigen (PSA) levels in blood are widely used and associated with prostate cancer risk and outcome. After puberty, PSA levels increase by age and multiple single nucleotide polymorphisms (SNPs) have been found to be associated with PSA levels. However, the relationship between the effects of SNPs and age on PSA remains unknown. Methods: To test for SNP × age interaction, we conducted a genome-wide association study using 2394 men without prostate cancer diagnosis from Malmö, Sweden as a discovery set and 2137 men from the eMERGE study (USA) for validation. Linear regression was used to identify significant interactions between SNP and age (p < 1 × 10−4 for discovery, p <.05 for validation). Results: The 15 SNPs from three different loci (8p11.22, 8p12, 3q25.31) are found to have age-specific effect on PSA levels. Expression quantitative trait loci (eQTLs) analysis shows that 12 SNPs from 3q25.31 locus affect the expression level of three genes: KCNAB1, SLC33A1, PLCH1. Conclusions: Our results suggest that SNPs may have age-specific effect on PSA levels, which provides new direction to study genetic markers for PSA.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
eQTL, GWAS, prostate cancer, PSA, SNPs
in
Prostate
volume
80
issue
16
pages
8 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:32914890
  • scopus:85091377478
ISSN
0270-4137
DOI
10.1002/pros.24070
language
English
LU publication?
yes
id
b982a9e8-3be7-41ea-b9d0-e57f7bdd609f
date added to LUP
2020-11-03 12:23:15
date last changed
2024-03-20 18:43:43
@article{b982a9e8-3be7-41ea-b9d0-e57f7bdd609f,
  abstract     = {{<p>Background: Testing for prostate-specific antigen (PSA) levels in blood are widely used and associated with prostate cancer risk and outcome. After puberty, PSA levels increase by age and multiple single nucleotide polymorphisms (SNPs) have been found to be associated with PSA levels. However, the relationship between the effects of SNPs and age on PSA remains unknown. Methods: To test for SNP × age interaction, we conducted a genome-wide association study using 2394 men without prostate cancer diagnosis from Malmö, Sweden as a discovery set and 2137 men from the eMERGE study (USA) for validation. Linear regression was used to identify significant interactions between SNP and age (p &lt; 1 × 10<sup>−4</sup> for discovery, p &lt;.05 for validation). Results: The 15 SNPs from three different loci (8p11.22, 8p12, 3q25.31) are found to have age-specific effect on PSA levels. Expression quantitative trait loci (eQTLs) analysis shows that 12 SNPs from 3q25.31 locus affect the expression level of three genes: KCNAB1, SLC33A1, PLCH1. Conclusions: Our results suggest that SNPs may have age-specific effect on PSA levels, which provides new direction to study genetic markers for PSA.</p>}},
  author       = {{Li, Weiqiang and Bicak, Mesude and Sjoberg, Daniel D. and Vertosick, Emily and Dahlin, Anders and Melander, Olle and Ulmert, David and Lilja, Hans and Klein, Robert J.}},
  issn         = {{0270-4137}},
  keywords     = {{eQTL; GWAS; prostate cancer; PSA; SNPs}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{16}},
  pages        = {{1405--1412}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Prostate}},
  title        = {{Genome-wide association study identifies novel single nucleotide polymorphisms having age-specific effect on prostate-specific antigen levels}},
  url          = {{http://dx.doi.org/10.1002/pros.24070}},
  doi          = {{10.1002/pros.24070}},
  volume       = {{80}},
  year         = {{2020}},
}