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Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves cross-ancestry prediction

Hoffmann, Thomas J (author)
University of California, San Francisco
Graff, Rebecca E (author)
Madduri, Ravi K (author)
Argonne National Laboratory
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Rodriguez, Alex A (author)
Argonne National Laboratory
Cario, Clint L (author)
Stanford University School of Medicine
Feng, Karen (author)
Jiang, Yu (author)
Stanford University School of Medicine
Wang, Anqi (author)
University of Southern California
Klein, Robert J (author)
Icahn School of Medicine at Mount Sinai
Pierce, Brandon L (author)
Eggener, Scott (author)
Tong, Lin (author)
Blot, William (author)
Long, Jirong (author)
Rebbeck, Timothy (author)
Lachance, Joseph (author)
Andrews, Caroline (author)
Adebiyi, Akindele O (author)
Adusei, Ben (author)
Aisuodionoe-Shadrach, Oseremen I (author)
Fernandez, Pedro W (author)
Jalloh, Mohamed (author)
Janivara, Rohini (author)
Chen, Wenlong C (author)
Mensah, James E (author)
Agalliu, Ilir (author)
Berndt, Sonja I (author)
Shelley, John P (author)
Schaffer, Kerry (author)
Machiela, Mitchell J (author)
Freedman, Neal D (author)
Huang, Wen-Yi (author)
Li, Shengchao A (author)
Goodman, Phyllis J (author)
Till, Cathee (author)
Thompson, Ian (author)
Lilja, Hans (author)
Lund 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
Van Den Eeden, Stephen K (author)
Chanock, Stephen J (author)
Mosley, Jonathan D (author)
Conti, David V (author)
Haiman, Christopher A (author)
Justice, Amy C (author)
Kachuri, Linda (author)
Witte, John S (author)
Stanford University
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 (creator_code:org_t)
2023
English.
Related links:
http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Other publication (other academic/artistic)
Abstract Subject headings
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  • We conducted a multi-ancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry; 58,236 African ancestry; 23,546 Hispanic/Latino; 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (p≤5e-8) variants, 184 of which were novel. Most demonstrated evidence of replication in an independent cohort (n=95,768). Meta-analyzing discovery and replication (n=392,522) identified 447 variants, of which a further 111 were novel. Out-of-sample variance in PSA explained by our new polygenic risk score reached 16.9% (95% CI=16.1%-17.8%) in European ancestry, 9.5% (95% CI=7.0%-12.2%) in African ancestry, 18.6% (95% CI=15.8%-21.4%) in Hispanic/Latino, and 15.3% (95% CI=12.7%-18.1%) in Asian ancestry, and lower for higher age. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, with potential to personalize prostate cancer screening.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Publication and Content Type

ovr (subject category)
vet (subject category)

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