Skip to main content

Master of Public Health

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

AUTHORS

Mosley JD , Shelley JP , Dickson AL , Zanussi J , Daniel LL , Zheng NS , Bastarache L , Wei WQ , Shi M , Jarvik GP , Rosenthal EA , Khan A , Sherafati A , Kullo IJ , Walunas TL , Glessner J , Hakonarson H , Cox NJ , Roden DM , Frangakis SG , Vanderwerff B , Stein CM , Van Driest SL , Borinstein SC , Shu XO , Zawistowski M , Chung CP , Kawai VK , . Nature communications. 2024 4 22; 15(1). 3384

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 (PGS) 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 PGS [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) 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.

Tags: