دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Clinical associations with a polygenic predisposition to benign lower white blood cell counts.
المؤلفون: Mosley JD; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. jonathan.d.mosley@vumc.org.; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA. jonathan.d.mosley@vumc.org., Shelley JP; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA., Dickson AL; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Zanussi J; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Daniel LL; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Zheng NS; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Yale School of Medicine, New Haven, CT, USA., Bastarache L; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA., Wei WQ; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA., Shi M; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA., Jarvik GP; Department of Genome Sciences, University of Washington Medical Center, Seattle, WA, USA.; Department of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA, USA., Rosenthal EA; Department of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA, USA., Khan A; Division of Nephrology, Dept of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA., Sherafati A; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA., Kullo IJ; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA., Walunas TL; Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Glessner J; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Hakonarson H; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Cox NJ; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Roden DM; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA., Frangakis SG; Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA., Vanderwerff B; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA., Stein CM; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA., Van Driest SL; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA., Borinstein SC; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA., Shu XO; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Zawistowski M; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA., Chung CP; Department of Medicine, University of Miami, Miami, FL, USA., Kawai VK; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
المصدر: Nature communications [Nat Commun] 2024 Apr 22; Vol. 15 (1), pp. 3384. Date of Electronic Publication: 2024 Apr 22.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Genetic Predisposition to Disease* , Polymorphism, Single Nucleotide* , Multifactorial Inheritance* , Leukopenia*/genetics , Leukopenia*/blood, Humans ; Leukocyte Count ; Male ; Female ; Middle Aged ; Aged ; Adult ; Immunosuppressive Agents/therapeutic use
مستخلص: 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 WBC ) 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 WBC [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.
(© 2024. The Author(s).)
التعليقات: Update of: medRxiv. 2023 Aug 21;:. (PMID: 37662324)
References: Hum Mol Genet. 2014 Dec 20;23(25):6944-60. (PMID: 25096241)
Bioinformatics. 2012 Dec 15;28(24):3326-8. (PMID: 23060615)
JAMA Oncol. 2018 Mar 1;4(3):413-414. (PMID: 29423505)
J Cell Mol Med. 2022 Jul;26(13):3628-3635. (PMID: 35642720)
PLoS Genet. 2011 Jun;7(6):e1002108. (PMID: 21738479)
Nat Protoc. 2014 Nov;9(11):2643-62. (PMID: 25321409)
Nat Commun. 2023 Sep 8;14(1):5536. (PMID: 37684235)
Genet Epidemiol. 2019 Feb;43(1):63-81. (PMID: 30298529)
JAMA Intern Med. 2021 Aug 1;181(8):1100-1105. (PMID: 34180972)
N Engl J Med. 2014 Dec 25;371(26):2488-98. (PMID: 25426837)
Hematology Am Soc Hematol Educ Program. 2012;2012:174-82. (PMID: 23233578)
Nat Genet. 2016 Oct;48(10):1279-83. (PMID: 27548312)
Nat Commun. 2016 Apr 25;7:11433. (PMID: 27109359)
Biochem Med (Zagreb). 2016;26(1):5-16. (PMID: 26981015)
Nat Genet. 2022 Aug;54(8):1155-1166. (PMID: 35835912)
J Appl Lab Med. 2018 Nov 1;3(3):366-377. (PMID: 33636914)
Nat Commun. 2014 Aug 22;5:4684. (PMID: 25147954)
Genet Epidemiol. 2011 Dec;35(8):887-98. (PMID: 22125226)
Genet Med. 2013 Oct;15(10):761-71. (PMID: 23743551)
Bioinformatics. 2014 Oct 15;30(20):2906-14. (PMID: 24990607)
NPJ Precis Oncol. 2021 May 21;5(1):40. (PMID: 34021222)
Genet Med. 2019 Aug;21(8):1705-1707. (PMID: 30635622)
Bioinformatics. 2010 May 1;26(9):1205-10. (PMID: 20335276)
Cancer Med. 2021 Oct;10(19):6767-6776. (PMID: 34547180)
Ann Intern Med. 2022 Aug;175(8):1092-1099. (PMID: 35724382)
Sci Transl Med. 2017 May 10;9(389):. (PMID: 28490672)
PLoS Genet. 2009 Jan;5(1):e1000360. (PMID: 19180233)
Cell. 2016 Nov 17;167(5):1415-1429.e19. (PMID: 27863252)
JMIR Med Inform. 2019 Nov 29;7(4):e14325. (PMID: 31553307)
Nucleic Acids Res. 2019 Jan 8;47(D1):D1005-D1012. (PMID: 30445434)
Nature. 2020 Oct;586(7831):769-775. (PMID: 33057200)
Hematology Am Soc Hematol Educ Program. 2012;2012:485-91. (PMID: 23233623)
Cell. 2020 Sep 3;182(5):1198-1213.e14. (PMID: 32888493)
Mol Psychiatry. 2019 Mar;24(3):328-337. (PMID: 30647433)
J Clin Psychiatry. 2016 Jul;77(7):e909-16. (PMID: 27464332)
Rheumatology (Oxford). 2021 Nov 3;60(11):5185-5193. (PMID: 33693676)
Public Health Rep. 1978 Mar-Apr;93(2):150-2. (PMID: 635089)
Nature. 2009 Aug 6;460(7256):748-52. (PMID: 19571811)
Clin Pharmacol Ther. 2008 Sep;84(3):362-9. (PMID: 18500243)
Am J Hum Genet. 2007 Sep;81(3):559-75. (PMID: 17701901)
Nat Genet. 2018 Sep;50(9):1219-1224. (PMID: 30104762)
PLoS One. 2017 Jul 7;12(7):e0175508. (PMID: 28686612)
Nat Genet. 1995 Jun;10(2):224-8. (PMID: 7663520)
J Natl Cancer Inst. 2003 Oct 15;95(20):1545-8. (PMID: 14559877)
Nat Rev Genet. 2018 Sep;19(9):581-590. (PMID: 29789686)
Cell Genom. 2023 Jan 31;3(2):100257. (PMID: 36819667)
معلومات مُعتمدة: U01 HG006385 United States HG NHGRI NIH HHS; UL1 TR000445 United States TR NCATS NIH HHS; S10 RR025141 United States RR NCRR NIH HHS; U01 HG004424 United States HG NHGRI NIH HHS; U01 HG006389 United States HG NHGRI NIH HHS; U01 HG006828 United States HG NHGRI NIH HHS; U01 HG006380 United States HG NHGRI NIH HHS; RC2 GM092618 United States GM NIGMS NIH HHS; P50 GM115305 United States GM NIGMS NIH HHS; U01 HG006379 United States HG NHGRI NIH HHS; U01 HG011181 United States HG NHGRI NIH HHS; R35 GM131770 United States GM NIGMS NIH HHS; R01 GM130791 United States GM NIGMS NIH HHS; U01 HG006830 United States HG NHGRI NIH HHS; U01 HG006375 United States HG NHGRI NIH HHS; U01 HG004438 United States HG NHGRI NIH HHS; U01 HG006382 United States HG NHGRI NIH HHS; U19 HL065962 United States HL NHLBI NIH HHS; R01 GM126535 United States GM NIGMS NIH HHS; R01 HD074711 United States HD NICHD NIH HHS; U01 HG006388 United States HG NHGRI NIH HHS; U01 HG006378 United States HG NHGRI NIH HHS; UL1 RR024975 United States RR NCRR NIH HHS; R01 NS032830 United States NS NINDS NIH HHS; U01 HG004798 United States HG NHGRI NIH HHS; UL1 TR002243 United States TR NCATS NIH HHS
المشرفين على المادة: 0 (Immunosuppressive Agents)
تواريخ الأحداث: Date Created: 20240422 Date Completed: 20240424 Latest Revision: 20240506
رمز التحديث: 20240506
مُعرف محوري في PubMed: PMC11035609
DOI: 10.1038/s41467-024-47804-5
PMID: 38649760
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-024-47804-5