Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer.
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California 94158, USA.
- Division of Research, Kaiser Permanente, Northern California, Oakland, California 94612, USA.
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California 91101, USA.
- Department of Urology, Kaiser Oakland Medical Center, Northern California, Oakland, California 94612, USA.
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden.
- Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20814, USA.
- Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA.
- Icahn Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029 USA.
- Departments of Laboratory Medicine, Surgery, and Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
- Department of Clinical Sciences, Lund University, Malmö 205 02, Sweden.
- Institute for Human Genetics, University of California San Francisco, San Francisco, California 94143, USA.
Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa-such as genetics-can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente whites and 17,428 men from replication cohorts. We detect 40 genome-wide significant (P<5 × 10-8) single-nucleotide polymorphisms (SNPs): 19 novel, 15 previously identified for PSA (14 of which were also PCa-associated), and 6 previously identified for PCa only. Further analysis incorporating PCa cases suggests that at least half of the 40 SNPs are PSA-associated independent of PCa. The 40 SNPs explain 9.5% of PSA variation in non-Hispanic whites, and the remaining GWAS SNPs explain an additional 31.7%; this percentage is higher in younger men, supporting the genetic basis of PSA levels. These findings provide important information about genetic markers for PSA that may improve PCa screening, thereby reducing over-diagnosis and over-treatment.