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

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.

Bicak, MesudeIcahn School of Medicine at Mount Sinai (author)
Sjoberg, Daniel D.Memorial Sloan-Kettering Cancer Center (author)
Vertosick, EmilyMemorial Sloan-Kettering Cancer Center (author)
Dahlin, AndersLund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups(Swepub:lu)infl-ada (author)
Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome (author)
Ulmert, DavidMemorial Sloan-Kettering Cancer Center(Swepub:lu)klke-dul (author)
Lilja, HansLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Clinical Chemistry, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Memorial Sloan-Kettering Cancer Center(Swepub:lu)klke-hli (author)
Klein, Robert J.Icahn School of Medicine at Mount Sinai (author)
Icahn School of Medicine at Mount SinaiMemorial Sloan-Kettering Cancer Center (creator_code:org_t)

By the author/editor: Li, Weiqiang; Bicak, Mesude; Sjoberg, Daniel ...; Vertosick, Emily; Dahlin, Anders; Melander, Olle; show more...; Ulmert, David; Lilja, Hans; Klein, Robert J.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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