Evidence map›Paper›PMID 33236004›Full record

ArticleResearch square2020

Hematopoietic mosaic chromosomal alterations and risk for infection among 767,891 individuals without blood cancer.

Pradeep Natarajan, Seyedeh Zekavat, Shu-Hong Lin, Alexander Bick, Aoxing Liu, Kaavya Paruchuri, Md Mesbah Uddin, Yixuan Ye, Zhaolong Yu, Xiaoxi Liu and 21 more

Open access · greenAbstract readPreprint
In one paragraph

Article in Research square, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 6 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 11 institutions in 3 countries.

Pradeep Natarajan
Seyedeh Zekavat
Shu-Hong Lin
Alexander Bick
Aoxing Liu
Kaavya Paruchuri
Md Mesbah Uddin
Yixuan Ye
Zhaolong Yu
Xiaoxi Liu
Yoichiro Kamatani
Puja Kohli
Eric Engels
Derek Brown
Jordan Smoller
Robert Green
Elizabeth Karlson
Matthew Lebo
Scott Weiss
Mark Daly
Massachusetts General Hospital · USBrigham and Women's Hospital · USYale University · USBroad Institute · USHarvard University · USInstitute for Molecular Medicine Finland · FIDana-Farber Cancer Institute · USKyoto University · JPRIKEN · JPRIKEN Center for Integrative Medical Sciences · JPVanderbilt University Medical Center · US

Funding

IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6M
African Ancestry Genomic Psychiatry CohortR01MH104964 · NIMH · SUNY DOWNSTATE MEDICAL CENTER · PI BIGDELI, TIM BERNARD, FANOUS, AYMAN H · 2015 to 2024
$16.7M
Medical Scientist Training ProgramT32GM136651 · NIGMS · YALE UNIVERSITY · PI BARBARA I KAZMIERCZAK · 2020 to 2026
$16.5M
MULTIDISCIPLINARY RESEARCH TRAINING IN CARDIOLOGYT32HL007208 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Patrick Thomas Ellinor, David E Sosnovik · 1985 to 2026
$16.1M
Structurally complex genome loci in human populations and human phenotypesR01HG006855 · NHGRI · HARVARD MEDICAL SCHOOL · PI Steven Andrew McCarroll · 2012 to 2026
$8.2M
Clonal hematopoiesis in the Womens Health Initiative Memory StudyR01HL148565 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ALEXANDER P REINER, Eric A. Whitsel · 2019 to 2026
$5.9M
Clonal hematopoiesis in humans: determinants of development and progressionR01HL148050 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI BALLANTYNE, CHRISTIE MITCHELL, NATARAJAN, PRADEEP · 2019 to 2022
$5.9M
AFGen Consortium: Atrial Fibrillation Genomics to Functional AnalysesR01HL128914 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2015 to 2018
$3.1M
Revealing somatic genome alterations and their clinical sequelae: Ultrasensitive computational detection of mosaic structural variantsDP2ES030554 · NIEHS · BRIGHAM AND WOMEN'S HOSPITAL · PI LOH, PO-RU · 2018 to 2018
$2.7M
Mentoring in Arrhythmia ResearchK24HL105780 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2011 to 2020
$1.2M
Dissecting the impact of clonal hematopoiesis on atherosclerosis using multiscale 'omicsF30HL149180 · NHLBI · YALE UNIVERSITY · PI ZEKAVAT, SEYEDEH MARYAM · 2019 to 2021
$138k
6 · The paper itself

Abstract

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.

Identifiers

PMID33236004
PMCPMC7685327
OpenAlexW3104827422

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.