Genetic survey of biomarkers across pregnancy identifies pregnancy-specialized immune regulation
Much remains unknown about the genetics of immune system changes during pregnancy. We used SNP data in a pregnancy cohort to genetically investigate 47 immune biomarkers at two timepoints, along with change between timepoints (delta). We identified 19 biomarkers with significant SNP-based heritability and 34 with genome-wide significant signals, demonstrating genetic regulation. The same biomarkers measured in early- and mid-pregnancy shared about half of significant associations across timepoints, with enrichment for immune pathways. In contrast, delta showed enrichment in transcription factors and developmental processes. About half of suggestive associations overlapped with non-pregnancy associations. However, these data leave a substantial fraction of potentially timepoint-specific and pregnancy-unique findings. Nearby genes were enriched for placental expression, reinforcing the novelty of our results. We additionally explored the relationship between immune genetic associations and prior GWAS of pregnancy complications. Overall, we present the first multi-timepoint genetic study of immune profile in pregnancy.
Authors
- Elizabeth Sahagún (ORCID: https://orcid.org/0000-0002-9994-8779)
- Jennifer Ames (ORCID: https://orcid.org/0000-0003-0906-9162)
- Lisa Croen (ORCID: https://orcid.org/0000-0001-7849-9428)
- Yinge Qian
- Jane W. Liang (ORCID: https://orcid.org/0000-0002-2302-3809)
- Paul Ashwood (ORCID: https://orcid.org/0000-0002-4255-1893)
- Michela Traglia (ORCID: https://orcid.org/0000-0002-3361-4602)
- Luke P. Grosvenor (ORCID: https://orcid.org/0000-0002-8643-5894)
- Erica P. Gunderson (ORCID: https://orcid.org/0000-0002-2039-1964)
- Merve Çakır (ORCID: https://orcid.org/0000-0003-1803-5693)
- Robert H. Yolken (ORCID: https://orcid.org/0000-0001-9902-1554)
- Stacey Alexeeff
- Judy Van de Water
- Danielle HJ Kim
- Lauren A. Weiss
Institutions
- Gladstone Institutes (US)
- Kaiser Permanente (US)
- Johns Hopkins University (US)
- University of California, San Francisco (US)
- Johns Hopkins Medicine (US)
- University of California Davis Medical Center (US)
- University of California, Davis (US)
Publication Details
- Journal
- medRxiv
- Published
- 2026-01-02
- DOI
- https://doi.org/10.64898/2025.12.31.25343052
- Primary Topic
- Reproductive System and Pregnancy
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ellison Medical Foundation
- Wayne and Gladys Valley Foundation
- Kaiser Permanente
- National Institutes of Health
- National Institute of Child Health and Human Development