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Genetic variation in the human leukocyte antigen region confers susceptibility to Clostridioides difficile infection

by de Andrade, Mariza , Jarvik, Gail P. , Crane, Paul K. , Connolly, John J. , Crenshaw, Andrew T. , McCarty, Catherine A. , Carrell, David , Rowley, Robb , Hakonarson, Hakon , Luo, Yuan , Satterfield, Benjamin A. , Karlson, Elizabeth W. , Crawford, Dana C. , Mirel, Daniel B. , Li, Rongling , Ferar, Kathleen , Carlson, Christopher , Dikilitas, Ozan , Ritchie, Marylyn D. , Denny, Joshua C. , Hall, Taryn O. , Gragert, Loren , Crosslin, David R. , Kullo, Iftikhar J. , Kho, Abel , Hayes, M. Geoffrey

in 631/208/205/2138 / 631/250/21/324/1508 / 692/308/2056 / 692/699/255/1911 / Antibiotics / Antigens / Association analysis / Biology / Chemotherapy / Clostridioides difficile / Clostridium Infections - genetics / Diarrhea / Electronic health records / Electronic medical records / Gene regulation / Genetic diversity / Genetic variance / Genetic Variation / Genetics / Genome-Wide Association Study / Genomes / Genomics / Health sciences / Histocompatibility antigen HLA / Histocompatibility Antigens / Histocompatibility Antigens Class II / HLA Antigens - genetics / Hospitals / Humanities and Social Sciences / Humans / Infections / Informatics / Internal medicine / Leukocytes / Major histocompatibility complex / Medical records / Medical research / Morbidity / Mortality / multidisciplinary / Opportunist infection / Patients / Preventive medicine / Recurrent infection / Regression analysis / Research centers / Risk factors / Science / Science (multidisciplinary) / Susceptibility

2023

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Genetic variation in the human leukocyte antigen region confers susceptibility to Clostridioides difficile infection

2023

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2023

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Journal Article

Genetic variation in the human leukocyte antigen region confers susceptibility to Clostridioides difficile infection

de Andrade, Mariza,

Jarvik, Gail P.,

Crane, Paul K.,

Connolly, John J.,

Crenshaw, Andrew T.,

McCarty, Catherine A.,

Carrell, David,

Rowley, Robb,

Hakonarson, Hakon,

Luo, Yuan,

Satterfield, Benjamin A.,

Karlson, Elizabeth W.,

Crawford, Dana C.,

Mirel, Daniel B.,

Li, Rongling,

Ferar, Kathleen,

Carlson, Christopher,

Dikilitas, Ozan,

Ritchie, Marylyn D.,

Denny, Joshua C.,

Hall, Taryn O.,

Gragert, Loren,

Crosslin, David R.,

Kullo, Iftikhar J.,

Kho, Abel,

Hayes, M. Geoffrey

2023

Overview

Clostridioides difficile ( C. diff. ) infection (CDI) is a leading cause of hospital acquired diarrhea in North America and Europe and a major cause of morbidity and mortality. Known risk factors do not fully explain CDI susceptibility, and genetic susceptibility is suggested by the fact that some patients with colons that are colonized with C. diff. do not develop any infection while others develop severe or recurrent infections. To identify common genetic variants associated with CDI, we performed a genome-wide association analysis in 19,861 participants (1349 cases; 18,512 controls) from the Electronic Medical Records and Genomics (eMERGE) Network. Using logistic regression, we found strong evidence for genetic variation in the DRB locus of the MHC (HLA) II region that predisposes individuals to CDI (P > 1.0 × 10 –14 ; OR 1.56). Altered transcriptional regulation in the HLA region may play a role in conferring susceptibility to this opportunistic enteric pathogen.

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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

631/208/205/2138

/ 631/250/21/324/1508

/ Association analysis