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Discovery of novel ancestry specific genes for androgens and hypogonadism in Million Veteran Program Men

Author

Listed:
  • Meghana S. Pagadala

    (VA San Diego Healthcare System
    University of California San Diego
    University of California San Diego)

  • Craig C. Teerlink

    (VA Salt Lake City Healthcare System
    University of Utah School of Medicine)

  • Guneet K. Jasuja

    (VA Bedford Healthcare System
    Boston University School of Medicine
    Boston University School of Public Health)

  • Madhuri Palnati

    (VA Bedford Healthcare System)

  • Tori Anglin-Foote

    (VA Salt Lake City Healthcare System)

  • Nai-Chung N. Chang

    (VA Salt Lake City Healthcare System)

  • Rishi Deka

    (VA San Diego Healthcare System
    University of California San Diego
    University of California San Diego)

  • Kyung M. Lee

    (VA Salt Lake City Healthcare System)

  • Fatai Y. Agiri

    (VA Salt Lake City Healthcare System)

  • Tiffany Amariuta

    (University of California San Diego
    University of California San Diego)

  • Tyler M. Seibert

    (VA San Diego Healthcare System
    University of California San Diego
    University of California San Diego
    University of California San Diego)

  • Brent S. Rose

    (VA San Diego Healthcare System
    University of California San Diego
    University of California San Diego)

  • Kathryn M. Pridgen

    (VA Salt Lake City Healthcare System)

  • Julie A. Lynch

    (VA Salt Lake City Healthcare System
    University of Utah School of Medicine)

  • Hannah K. Carter

    (University of California San Diego)

  • Matthew S. Panizzon

    (VA San Diego Healthcare System
    University of California San Diego
    University of California San Diego)

  • Richard L. Hauger

    (University of California San Diego
    University of California San Diego
    VA San Diego Healthcare System)

Abstract

Given the various roles of testosterone in men’s health, we conducted a multi-ancestral genetic analysis of total testosterone, free testosterone, SHBG, and hypogonadism in men within the Million Veteran Program (MVP). Here we identified 157 significant testosterone genetic variants, of which 8 have significant ancestry-specific associations. These variants implicate several genes, including SERPINF2, PRPF8, BAIAP2L1, SHBG, PRMT6, and PPIF, related to liver function. Genetic regulators of testosterone have cell type-specific effects in the testes, liver, and adrenal gland and are associated with disease risk. We conducted a meta-analysis amongst ancestry groups to identify 188 variants significantly associated with testosterone, of which 22 are novel associations. We constructed genetic scores for total testosterone, SHBG levels, and hypogonadism and find that men with higher testosterone genetic scores have lower odds of diabetes, hyperlipidemia, gout, and cardiac disorders. These findings provide insight into androgen regulation and identify novel variants for disease risk stratification.

Suggested Citation

  • Meghana S. Pagadala & Craig C. Teerlink & Guneet K. Jasuja & Madhuri Palnati & Tori Anglin-Foote & Nai-Chung N. Chang & Rishi Deka & Kyung M. Lee & Fatai Y. Agiri & Tiffany Amariuta & Tyler M. Seibert, 2025. "Discovery of novel ancestry specific genes for androgens and hypogonadism in Million Veteran Program Men," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57372-x
    DOI: 10.1038/s41467-025-57372-x
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    References listed on IDEAS

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    3. Claudia Giambartolomei & Damjan Vukcevic & Eric E Schadt & Lude Franke & Aroon D Hingorani & Chris Wallace & Vincent Plagnol, 2014. "Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics," PLOS Genetics, Public Library of Science, vol. 10(5), pages 1-15, May.
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