Hematopoietic mosaic chromosomal alterations and risk for infection among 767,891 individuals without blood cancer
Seyedeh Maryam Zekavat,
Alexander G Bick,
Md Mesbah Uddin,
Steven A McCarroll,
Eric A. Engels,
Derek W. Brown,
Jordan W. Smoller,
Elizabeth W. Karlson,
Patrick T. Ellinor,
Scott T. Weiss,
Mark J. Daly,
The Biobank Japan Project,
Benjamin L Ebert,
COVID-19 Host Genetics Initiative,
Mitchell J. Machiela,
Posted 16 Nov 2020
medRxiv DOI: 10.1101/2020.11.12.20230821
Posted 16 Nov 2020
Summary ParagraphAge is the dominant risk factor for infectious diseases, but the mechanisms linking the two are incompletely understood1,2. Age-related mosaic chromosomal alterations (mCAs) detected from blood-derived DNA genotyping, are structural somatic variants associated with aberrant leukocyte cell counts, hematological malignancy, and mortality3-11. Whether mCAs represent independent risk factors for infection is unknown. Here we use genome-wide genotyping of blood DNA to show that mCAs predispose to diverse infectious diseases. We analyzed mCAs from 767,891 individuals without hematological cancer at DNA acquisition across four countries. Expanded mCA (cell fraction >10%) prevalence approached 4% by 60 years of age and was associated with diverse incident infections, including sepsis, pneumonia, and coronavirus disease 2019 (COVID-19) hospitalization. A genome-wide association study of expanded mCAs identified 63 significant loci. Germline genetic alleles associated with expanded mCAs were enriched at transcriptional regulatory sites for immune cells. Our results link mCAs with impaired immunity and predisposition to infections. Furthermore, these findings may also have important implications for the ongoing COVID-19 pandemic, particularly in prioritizing individual preventive strategies and evaluating immunization responses.
- Downloaded 1,122 times
- Download rankings, all-time:
- Site-wide: 20,636
- In genetic and genomic medicine: 81
- Year to date:
- Site-wide: 6,031
- Since beginning of last month:
- Site-wide: 50,754
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!