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Hematopoietic mosaic chromosomal alterations and risk for infection among 767,891 individuals without blood cancer
Age 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, he...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685327/ https://www.ncbi.nlm.nih.gov/pubmed/33236004 http://dx.doi.org/10.21203/rs.3.rs-100817/v1 |
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author | Natarajan, Pradeep Zekavat, Seyedeh Lin, Shu-Hong Bick, Alexander Liu, Aoxing Paruchuri, Kaavya Uddin, Md Mesbah Ye, Yixuan Yu, Zhaolong Liu, Xiaoxi Kamatani, Yoichiro Pirruccello, James Pampana, Akhil Loh, Po-Ru Kohli, Puja McCarroll, Steven Neale, Benjamin Engels, Eric Brown, Derek Smoller, Jordan Green, Robert Karlson, Elizabeth Lebo, Matthew Ellinor, Patrick Weiss, Scott Daly, Mark Terao, Chikashi Zhao, Hongyu Ebert, Benjamin Machiela, Mitchell Genovese, Giulio |
author_facet | Natarajan, Pradeep Zekavat, Seyedeh Lin, Shu-Hong Bick, Alexander Liu, Aoxing Paruchuri, Kaavya Uddin, Md Mesbah Ye, Yixuan Yu, Zhaolong Liu, Xiaoxi Kamatani, Yoichiro Pirruccello, James Pampana, Akhil Loh, Po-Ru Kohli, Puja McCarroll, Steven Neale, Benjamin Engels, Eric Brown, Derek Smoller, Jordan Green, Robert Karlson, Elizabeth Lebo, Matthew Ellinor, Patrick Weiss, Scott Daly, Mark Terao, Chikashi Zhao, Hongyu Ebert, Benjamin Machiela, Mitchell Genovese, Giulio |
author_sort | Natarajan, Pradeep |
collection | PubMed |
description | Age 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. |
format | Online Article Text |
id | pubmed-7685327 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-76853272020-11-25 Hematopoietic mosaic chromosomal alterations and risk for infection among 767,891 individuals without blood cancer Natarajan, Pradeep Zekavat, Seyedeh Lin, Shu-Hong Bick, Alexander Liu, Aoxing Paruchuri, Kaavya Uddin, Md Mesbah Ye, Yixuan Yu, Zhaolong Liu, Xiaoxi Kamatani, Yoichiro Pirruccello, James Pampana, Akhil Loh, Po-Ru Kohli, Puja McCarroll, Steven Neale, Benjamin Engels, Eric Brown, Derek Smoller, Jordan Green, Robert Karlson, Elizabeth Lebo, Matthew Ellinor, Patrick Weiss, Scott Daly, Mark Terao, Chikashi Zhao, Hongyu Ebert, Benjamin Machiela, Mitchell Genovese, Giulio Res Sq Article Age 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. American Journal Experts 2020-11-16 /pmc/articles/PMC7685327/ /pubmed/33236004 http://dx.doi.org/10.21203/rs.3.rs-100817/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Natarajan, Pradeep Zekavat, Seyedeh Lin, Shu-Hong Bick, Alexander Liu, Aoxing Paruchuri, Kaavya Uddin, Md Mesbah Ye, Yixuan Yu, Zhaolong Liu, Xiaoxi Kamatani, Yoichiro Pirruccello, James Pampana, Akhil Loh, Po-Ru Kohli, Puja McCarroll, Steven Neale, Benjamin Engels, Eric Brown, Derek Smoller, Jordan Green, Robert Karlson, Elizabeth Lebo, Matthew Ellinor, Patrick Weiss, Scott Daly, Mark Terao, Chikashi Zhao, Hongyu Ebert, Benjamin Machiela, Mitchell Genovese, Giulio Hematopoietic mosaic chromosomal alterations and risk for infection among 767,891 individuals without blood cancer |
title |
Hematopoietic mosaic chromosomal alterations and risk for infection among 767,891 individuals without blood cancer
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title_full |
Hematopoietic mosaic chromosomal alterations and risk for infection among 767,891 individuals without blood cancer
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title_fullStr |
Hematopoietic mosaic chromosomal alterations and risk for infection among 767,891 individuals without blood cancer
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title_full_unstemmed |
Hematopoietic mosaic chromosomal alterations and risk for infection among 767,891 individuals without blood cancer
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title_short |
Hematopoietic mosaic chromosomal alterations and risk for infection among 767,891 individuals without blood cancer
|
title_sort | hematopoietic mosaic chromosomal alterations and risk for infection among 767,891 individuals without blood cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685327/ https://www.ncbi.nlm.nih.gov/pubmed/33236004 http://dx.doi.org/10.21203/rs.3.rs-100817/v1 |
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