Hematologic setpoints are a stable and patient-specific deep phenotype.
| العنوان: | Hematologic setpoints are a stable and patient-specific deep phenotype. |
|---|---|
| المؤلفون: | Foy BH; Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA.; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.; Department of Systems Biology, Harvard Medical School, Boston, MA, USA., Petherbridge R; Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA.; Department of Systems Biology, Harvard Medical School, Boston, MA, USA., Roth M; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Mow C; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.; Mass General Brigham Enterprise Research IS, Boston, MA, USA., Patel HR; Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA.; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Patel CH; Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA.; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Ho SN; Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA.; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Lam E; Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA.; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Karczewski KJ; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA., Tozzo V; Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA.; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.; Department of Systems Biology, Harvard Medical School, Boston, MA, USA., Higgins JM; Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA.; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.; Department of Systems Biology, Harvard Medical School, Boston, MA, USA. |
| المصدر: | MedRxiv : the preprint server for health sciences [medRxiv] 2023 Sep 28. Date of Electronic Publication: 2023 Sep 28. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | The complete blood count is an important screening tool for healthy adults and is the most commonly ordered test at periodic physical exams. However, results are usually interpreted relative to one-size-fits-all reference intervals, undermining the goal of precision medicine to tailor medical care to the needs of individual patients based on their unique characteristics. Here we show that standard complete blood count indices in healthy adults have robust homeostatic setpoints that are patient-specific and stable, with the typical healthy adult's set of 9 blood count setpoints distinguishable from 98% of others, and with these differences persisting for decades. These setpoints reflect a deep physiologic phenotype, enabling improved detection of both acquired and genetic determinants of hematologic regulation, including discovery of multiple novel loci via GWAS analyses. Patient-specific reference intervals derived from setpoints enable more accurate personalized risk assessment, and the setpoints themselves are significantly correlated with mortality risk, providing new opportunities to enhance patient-specific screening and early intervention. This study shows complete blood count setpoints are sufficiently stable and patient-specific to help realize the promise of precision medicine for healthy adults. Competing Interests: JMH reports funding from the National Institutes of Health (grant IDs: R01HD104756; R01DK123330). All authors report no conflicts of interest. |
| معلومات مُعتمدة: | R01 DK123330 United States DK NIDDK NIH HHS; R01 HD104756 United States HD NICHD NIH HHS |
| تواريخ الأحداث: | Date Created: 20231009 Latest Revision: 20240210 |
| رمز التحديث: | 20240210 |
| مُعرف محوري في PubMed: | PMC10557837 |
| DOI: | 10.1101/2023.09.26.23296146 |
| PMID: | 37808854 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2023.09.26.23296146 |
|---|