Five studies, the largest covering nearly 46,000 people, found dozens of loci shaping baseline PSA level as a continuous measurement — distinct from a prostate cancer diagnosis.
Prostate-specific antigen (PSA) is a protein produced by the prostate, measured in blood as a widely used (if imperfect) screening tool for prostate cancer. But PSA level varies continuously among men who do not have cancer at all — shaped by prostate size, inflammation, and genetics — which is exactly why understanding the genetic contribution to baseline PSA matters: a genetically higher baseline shifts what "elevated" should mean for that person, independent of cancer risk. This page covers that continuous measurement, distinct from this site's separate Prostate Cancer page.
Hoffmann et al. 2017, the largest and most PSA-specific of the studies behind this page, examined 28,503 Kaiser Permanente participants of European ancestry, replicated in 17,428 more. It found 40 genome-wide-significant variants: 19 entirely novel, 15 previously linked to PSA (14 of those also to prostate cancer risk), and 6 previously linked only to prostate cancer risk. A genetic risk score built from these loci explained an additional 31.7% of PSA variance beyond already-known factors — a larger effect in younger men. This page's rs11084596 in THEG5, rs16980679 in RAI2, rs4378355 in EHF, and rs8023057 in SERPINA3 all come directly from this study.
Four smaller or more specialized studies fill in the rest. Hu et al. 2013 ran a two-stage GWAS in Chinese men (1,999 then 1,496), confirming SLC45A3, MSMB, and KLK3 as PSA loci, with SLC45A3 newly identified in that population. Jin et al. 2013, in 3,192 European men, studied the free-PSA fraction specifically and found ATF7IP and KLK2 — this page's rs1354774, in KLK2, is that paper's own finding. Lee et al. 2015 ran a two-stage Korean study (554 then 1,575 men), finding 12 genome-wide-significant signals, with the top signal again near SLC45A3. And Gudmundsson et al. 2018, primarily a study of benign prostatic hyperplasia (20,621 cases, 280,541 controls), found that 15 of its 23 BPH-associated variants also affected PSA level, with a strong genetic correlation between the two traits — this page's rs381949, near CLPTM1L, is one of those overlapping variants.
PSA is measured directly with a blood test, and no variant on this page is used clinically to interpret a PSA result or diagnose prostate cancer. The variants here describe why baseline PSA varies among men generally — not who has, or will develop, prostate cancer.
PSA screening guidelines, thresholds, and follow-up (including biopsy decisions) are set by clinical practice, not genotype. For prostate cancer genetics specifically, see this site's separate Prostate Cancer page.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Prostate-Specific Antigen (PSA) Levels comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 9 of 9 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
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Prostate-Specific Antigen (PSA) Levels. MyGeneLog™. https://www.mygenelog.com/conditions/psa-levels
PSA is a protein made by the prostate, measured in blood as a screening tool for prostate cancer. PSA varies continuously even among men without cancer, shaped partly by genetics — which affects what counts as an "elevated" result for a given person.
Hoffmann et al. 2017, in 28,503 people replicated in 17,428 more, found 40 genome-wide-significant loci for PSA level, with a genetic risk score from these loci explaining an additional 31.7% of PSA variance.
No. This page covers genetic variants affecting baseline PSA level as a continuous measurement, distinct from this site's separate Prostate Cancer page, which covers disease-risk genetics.
No individual variant does. These are population-level statistical associations, and PSA is measured directly with a blood test, not estimated from genotype.
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