Clinical consequences of a polygenic predisposition to benign lower white blood cell counts : Consequences of benign WBC count genetics
Polygenic variation unrelated to disease contributes to interindividual variation in baseline white blood cell (WBC) counts, but its clinical significance is undefined. 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=1,724, 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 a WBC count polygenic score identifies individuals who are susceptible to escalations or alterations in clinical care that may be harmful or of little benefit.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
medRxiv : the preprint server for health sciences - (2023) vom: 21. Aug. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mosley, Jonathan D [VerfasserIn] |
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| Links: |
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| Themen: |
Azathioprine |
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| Anmerkungen: |
Date Revised 13.02.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2023.08.20.23294331 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361600437 |
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| 100 | 1 | |a Mosley, Jonathan D |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinical consequences of a polygenic predisposition to benign lower white blood cell counts |b Consequences of benign WBC count genetics |
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| 500 | |a Date Revised 13.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Polygenic variation unrelated to disease contributes to interindividual variation in baseline white blood cell (WBC) counts, but its clinical significance is undefined. 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=1,724, 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 a WBC count polygenic score identifies individuals who are susceptible to escalations or alterations in clinical care that may be harmful or of little benefit | ||
| 650 | 4 | |a Preprint | |
| 650 | 4 | |a White blood cell count | |
| 650 | 4 | |a azathioprine | |
| 650 | 4 | |a bone marrow biopsy | |
| 650 | 4 | |a pharmacogenomics | |
| 650 | 4 | |a polygenic score | |
| 650 | 4 | |a taxane | |
| 700 | 1 | |a Shelley, John P |e verfasserin |4 aut | |
| 700 | 1 | |a Dickson, Alyson L |e verfasserin |4 aut | |
| 700 | 1 | |a Zanussi, Jacy |e verfasserin |4 aut | |
| 700 | 1 | |a Daniel, Laura L |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Neil S |e verfasserin |4 aut | |
| 700 | 1 | |a Bastarache, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Wei-Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Mingjian |e verfasserin |4 aut | |
| 700 | 1 | |a Jarvik, Gail P |e verfasserin |4 aut | |
| 700 | 1 | |a Rosenthal, Elisabeth A |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Atlas |e verfasserin |4 aut | |
| 700 | 1 | |a Sherafati, Alborz |e verfasserin |4 aut | |
| 700 | 1 | |a Kullo, Iftikhar J |e verfasserin |4 aut | |
| 700 | 1 | |a Walunas, Theresa L |e verfasserin |4 aut | |
| 700 | 1 | |a Glessner, Joe |e verfasserin |4 aut | |
| 700 | 1 | |a Hakonarson, Hakon |e verfasserin |4 aut | |
| 700 | 1 | |a Cox, Nancy J |e verfasserin |4 aut | |
| 700 | 1 | |a Roden, Dan M |e verfasserin |4 aut | |
| 700 | 1 | |a Frangakis, Stephan G |e verfasserin |4 aut | |
| 700 | 1 | |a Vanderwerff, Brett |e verfasserin |4 aut | |
| 700 | 1 | |a Stein, C Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Van Driest, Sara L |e verfasserin |4 aut | |
| 700 | 1 | |a Borinstein, Scott C |e verfasserin |4 aut | |
| 700 | 1 | |a Shu, Xiao-Ou |e verfasserin |4 aut | |
| 700 | 1 | |a Zawistowski, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Cecilia P |e verfasserin |4 aut | |
| 700 | 1 | |a Kawai, Vivian K |e verfasserin |4 aut | |
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