Clinical associations with a polygenic predisposition to benign lower white blood cell counts

Jonathan D. Mosley (), John P. Shelley, Alyson L. Dickson, Jacy Zanussi, Laura L. Daniel, Neil S. Zheng, Lisa Bastarache, Wei-Qi Wei, Mingjian Shi, Gail P. Jarvik, Elisabeth A. Rosenthal, Atlas Khan, Alborz Sherafati, Iftikhar J. Kullo, Theresa L. Walunas, Joseph Glessner, Hakon Hakonarson, Nancy J. Cox, Dan M. Roden, Stephan G. Frangakis, Brett Vanderwerff, C. Michael Stein, Sara L. Van Driest, Scott C. Borinstein, Xiao-Ou Shu, Matthew Zawistowski, Cecilia P. Chung and Vivian K. Kawai
Additional contact information
Jonathan D. Mosley: Vanderbilt University Medical Center
John P. Shelley: Vanderbilt University Medical Center
Alyson L. Dickson: Vanderbilt University Medical Center
Jacy Zanussi: Vanderbilt University Medical Center
Laura L. Daniel: Vanderbilt University Medical Center
Neil S. Zheng: Vanderbilt University Medical Center
Lisa Bastarache: Vanderbilt University Medical Center
Wei-Qi Wei: Vanderbilt University Medical Center
Mingjian Shi: Vanderbilt University Medical Center
Gail P. Jarvik: University of Washington Medical Center
Elisabeth A. Rosenthal: University of Washington Medical Center
Atlas Khan: Columbia University
Alborz Sherafati: Mayo Clinic
Iftikhar J. Kullo: Mayo Clinic
Theresa L. Walunas: Northwestern University Feinberg School of Medicine
Joseph Glessner: Children’s Hospital of Philadelphia
Hakon Hakonarson: University of Pennsylvania
Nancy J. Cox: Vanderbilt University Medical Center
Dan M. Roden: Vanderbilt University Medical Center
Stephan G. Frangakis: University of Michigan Medical School
Brett Vanderwerff: University of Michigan
C. Michael Stein: Vanderbilt University Medical Center
Sara L. Van Driest: Vanderbilt University Medical Center
Scott C. Borinstein: Vanderbilt University Medical Center
Xiao-Ou Shu: Vanderbilt University Medical Center
Matthew Zawistowski: University of Michigan
Cecilia P. Chung: University of Miami
Vivian K. Kawai: Vanderbilt University Medical Center

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Polygenic variation unrelated to disease contributes to interindividual variation in baseline white blood cell (WBC) counts, but its clinical significance is uncharacterized. We investigated the clinical consequences of a genetic predisposition toward lower WBC counts among 89,559 biobank participants from tertiary care centers using a polygenic score for WBC count (PGSWBC) comprising single nucleotide polymorphisms not associated with disease. A predisposition to lower WBC counts was associated with a decreased risk of identifying pathology on a bone marrow biopsy performed for a low WBC count (odds-ratio = 0.55 per standard deviation increase in PGSWBC [95%CI, 0.30−0.94], p = 0.04), an increased risk of leukopenia (a low WBC count) when treated with a chemotherapeutic (n = 1724, hazard ratio [HR] = 0.78 [0.69−0.88], p = 4.0 × 10−5) or immunosuppressant (n = 354, HR = 0.61 [0.38–0.99], p = 0.04). A predisposition to benign lower WBC counts was associated with an increased risk of discontinuing azathioprine treatment (n = 1,466, HR = 0.62 [0.44−0.87], p = 0.006). Collectively, these findings suggest that there are genetically predisposed individuals who are susceptible to escalations or alterations in clinical care that may be harmful or of little benefit.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47804-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47804-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47804-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().