Eva Suarez-Pajes, Itahisa Marcelino-Rodriguez, Elisa Hernández Brito, Silvia Gonzalez-Barbuzano, Melody Ramirez-Falcon, Eva Tosco-Herrera, Luis A Rubio-Rodríguez, María Luisa Briones, Olga Rajas, Luis Borderías, Jose Ferreres, Antoni Payeras, Leonardo Lorente, Javier Aspa, Jose M Lorenzo Salazar, José Manuel Valencia-Gallardo, Nieves Carbonell, Jorge L Freixinet, Felipe Rodríguez de Castro, Jordi Solé Violán, Carlos Flores, Carlos Rodríguez-Gallego
{"title":"社区获得性肺炎成人全基因组关联研究。","authors":"Eva Suarez-Pajes, Itahisa Marcelino-Rodriguez, Elisa Hernández Brito, Silvia Gonzalez-Barbuzano, Melody Ramirez-Falcon, Eva Tosco-Herrera, Luis A Rubio-Rodríguez, María Luisa Briones, Olga Rajas, Luis Borderías, Jose Ferreres, Antoni Payeras, Leonardo Lorente, Javier Aspa, Jose M Lorenzo Salazar, José Manuel Valencia-Gallardo, Nieves Carbonell, Jorge L Freixinet, Felipe Rodríguez de Castro, Jordi Solé Violán, Carlos Flores, Carlos Rodríguez-Gallego","doi":"10.1186/s12931-024-03009-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Community-acquired pneumonia (CAP) is associated with high morbidity and hospitalization rate. In infectious diseases, host genetics plays a critical role in susceptibility and immune response, and the immune pathways involved are highly dependent on the microorganism and its route of infection. Here we aimed to identify genetic risk loci for CAP using a case-control genome-wide association study (GWAS).</p><p><strong>Methods: </strong>We performed a GWAS on 3,765 Spanish individuals, including 257 adult patients hospitalized with CAP and 3,508 population controls. Pneumococcal CAP was documented in 30% of patients; the remaining 70% were selected among patients with unidentified microbiological etiology. We tested 7,6 million imputed genotypes using logistic regressions. UK Biobank GWAS of bacterial pneumonia were used for results validation. Subsequently, we prioritized genes and likely causal variants based on Bayesian fine mapping and functional evidence. Imputation and association of classical HLA alleles and amino acids were also conducted.</p><p><strong>Results: </strong>Six independent sentinel variants reached the genome-wide significance (p < 5 × 10<sup>-8</sup>), three on chromosome 6p21.32, and one for each of the chromosomes 4q28.2, 11p12, and 20q11.22. Only one variant at 6p21.32 was validated in independent GWAS of bacterial and pneumococcal pneumonia. Our analyses prioritized C4orf33 on 4q28.2, TAPBP on 6p21.32, and ZNF341 on 20q11.22. Interestingly, genetic defects of TAPBP and ZNF341 are previously known inborn errors of immunity predisposing to bacterial pneumonia, including pneumococcus and Haemophilus influenzae. Associations were all non-significant for the classical HLA alleles.</p><p><strong>Conclusions: </strong>We completed a GWAS of CAP and identified four novel risk loci involved in CAP susceptibility.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"25 1","pages":"374"},"PeriodicalIF":5.8000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484206/pdf/","citationCount":"0","resultStr":"{\"title\":\"A genome-wide association study of adults with community-acquired pneumonia.\",\"authors\":\"Eva Suarez-Pajes, Itahisa Marcelino-Rodriguez, Elisa Hernández Brito, Silvia Gonzalez-Barbuzano, Melody Ramirez-Falcon, Eva Tosco-Herrera, Luis A Rubio-Rodríguez, María Luisa Briones, Olga Rajas, Luis Borderías, Jose Ferreres, Antoni Payeras, Leonardo Lorente, Javier Aspa, Jose M Lorenzo Salazar, José Manuel Valencia-Gallardo, Nieves Carbonell, Jorge L Freixinet, Felipe Rodríguez de Castro, Jordi Solé Violán, Carlos Flores, Carlos Rodríguez-Gallego\",\"doi\":\"10.1186/s12931-024-03009-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Community-acquired pneumonia (CAP) is associated with high morbidity and hospitalization rate. In infectious diseases, host genetics plays a critical role in susceptibility and immune response, and the immune pathways involved are highly dependent on the microorganism and its route of infection. Here we aimed to identify genetic risk loci for CAP using a case-control genome-wide association study (GWAS).</p><p><strong>Methods: </strong>We performed a GWAS on 3,765 Spanish individuals, including 257 adult patients hospitalized with CAP and 3,508 population controls. Pneumococcal CAP was documented in 30% of patients; the remaining 70% were selected among patients with unidentified microbiological etiology. We tested 7,6 million imputed genotypes using logistic regressions. UK Biobank GWAS of bacterial pneumonia were used for results validation. Subsequently, we prioritized genes and likely causal variants based on Bayesian fine mapping and functional evidence. Imputation and association of classical HLA alleles and amino acids were also conducted.</p><p><strong>Results: </strong>Six independent sentinel variants reached the genome-wide significance (p < 5 × 10<sup>-8</sup>), three on chromosome 6p21.32, and one for each of the chromosomes 4q28.2, 11p12, and 20q11.22. Only one variant at 6p21.32 was validated in independent GWAS of bacterial and pneumococcal pneumonia. Our analyses prioritized C4orf33 on 4q28.2, TAPBP on 6p21.32, and ZNF341 on 20q11.22. Interestingly, genetic defects of TAPBP and ZNF341 are previously known inborn errors of immunity predisposing to bacterial pneumonia, including pneumococcus and Haemophilus influenzae. Associations were all non-significant for the classical HLA alleles.</p><p><strong>Conclusions: </strong>We completed a GWAS of CAP and identified four novel risk loci involved in CAP susceptibility.</p>\",\"PeriodicalId\":49131,\"journal\":{\"name\":\"Respiratory Research\",\"volume\":\"25 1\",\"pages\":\"374\"},\"PeriodicalIF\":5.8000,\"publicationDate\":\"2024-10-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484206/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Respiratory Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12931-024-03009-4\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Respiratory Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12931-024-03009-4","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
A genome-wide association study of adults with community-acquired pneumonia.
Background: Community-acquired pneumonia (CAP) is associated with high morbidity and hospitalization rate. In infectious diseases, host genetics plays a critical role in susceptibility and immune response, and the immune pathways involved are highly dependent on the microorganism and its route of infection. Here we aimed to identify genetic risk loci for CAP using a case-control genome-wide association study (GWAS).
Methods: We performed a GWAS on 3,765 Spanish individuals, including 257 adult patients hospitalized with CAP and 3,508 population controls. Pneumococcal CAP was documented in 30% of patients; the remaining 70% were selected among patients with unidentified microbiological etiology. We tested 7,6 million imputed genotypes using logistic regressions. UK Biobank GWAS of bacterial pneumonia were used for results validation. Subsequently, we prioritized genes and likely causal variants based on Bayesian fine mapping and functional evidence. Imputation and association of classical HLA alleles and amino acids were also conducted.
Results: Six independent sentinel variants reached the genome-wide significance (p < 5 × 10-8), three on chromosome 6p21.32, and one for each of the chromosomes 4q28.2, 11p12, and 20q11.22. Only one variant at 6p21.32 was validated in independent GWAS of bacterial and pneumococcal pneumonia. Our analyses prioritized C4orf33 on 4q28.2, TAPBP on 6p21.32, and ZNF341 on 20q11.22. Interestingly, genetic defects of TAPBP and ZNF341 are previously known inborn errors of immunity predisposing to bacterial pneumonia, including pneumococcus and Haemophilus influenzae. Associations were all non-significant for the classical HLA alleles.
Conclusions: We completed a GWAS of CAP and identified four novel risk loci involved in CAP susceptibility.
期刊介绍:
Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases.
As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion.
Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.