Elena Kovalenko, Layal Shaheen, Ekaterina Vergasova, Alexey Kamelin, Valerya Rubinova, Dmitry Kharitonov, Anna Kim, Nikolay Plotnikov, Artem Elmuratov, Natalia Borovkova, Maya Storozheva, Sergey Solonin, Irina Gilyazova, Petr Mironov, Elza Khusnutdinova, Sergey Petrikov, Anna Ilinskaya, Valery Ilinsky, Alexander Rakitko
{"title":"东欧严重 COVID-19 的基因组分析和多基因风险评分。","authors":"Elena Kovalenko, Layal Shaheen, Ekaterina Vergasova, Alexey Kamelin, Valerya Rubinova, Dmitry Kharitonov, Anna Kim, Nikolay Plotnikov, Artem Elmuratov, Natalia Borovkova, Maya Storozheva, Sergey Solonin, Irina Gilyazova, Petr Mironov, Elza Khusnutdinova, Sergey Petrikov, Anna Ilinskaya, Valery Ilinsky, Alexander Rakitko","doi":"10.3389/fmed.2024.1409714","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>COVID-19 disease has infected more than 772 million people, leading to 7 million deaths. Although the severe course of COVID-19 can be prevented using appropriate treatments, effective interventions require a thorough research of the genetic factors involved in its pathogenesis.</p><p><strong>Methods: </strong>We conducted a genome-wide association study (GWAS) on 7,124 individuals (comprising 6,400 controls who had mild to moderate COVID-19 and 724 cases with severe COVID-19). The inclusion criteria were acute respiratory distress syndrome (ARDS), acute respiratory failure (ARF) requiring respiratory support, or CT scans indicative of severe COVID-19 infection without any competing diseases. We also developed a polygenic risk score (PRS) model to identify individuals at high risk.</p><p><strong>Results: </strong>We identified two genome-wide significant loci (<i>P</i>-value <5 × 10<sup>-8</sup>) and one locus with approximately genome-wide significance (<i>P</i>-value = 5.92 × 10<sup>-8</sup>-6.15 × 10<sup>-8</sup>). The most genome-wide significant variants were located in the <i>leucine zipper transcription factor like 1</i> (<i>LZTFL1</i>) gene, which has been highlighted in several previous GWAS studies. Our PRS model results indicated that individuals in the top 10% group of the PRS had twice the risk of severe course of the disease compared to those at median risk [odds ratio = 2.18 (1.66, 2.86), <i>P</i>-value = 8.9 × 10<sup>-9</sup>].</p><p><strong>Conclusion: </strong>We conducted one of the largest studies to date on the genetics of severe COVID-19 in an Eastern European cohort. Our results are consistent with previous research and will guide further epidemiologic studies on host genetics, as well as for the development of targeted treatments.</p>","PeriodicalId":12488,"journal":{"name":"Frontiers in Medicine","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446758/pdf/","citationCount":"0","resultStr":"{\"title\":\"GWAS and polygenic risk score of severe COVID-19 in Eastern Europe.\",\"authors\":\"Elena Kovalenko, Layal Shaheen, Ekaterina Vergasova, Alexey Kamelin, Valerya Rubinova, Dmitry Kharitonov, Anna Kim, Nikolay Plotnikov, Artem Elmuratov, Natalia Borovkova, Maya Storozheva, Sergey Solonin, Irina Gilyazova, Petr Mironov, Elza Khusnutdinova, Sergey Petrikov, Anna Ilinskaya, Valery Ilinsky, Alexander Rakitko\",\"doi\":\"10.3389/fmed.2024.1409714\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>COVID-19 disease has infected more than 772 million people, leading to 7 million deaths. Although the severe course of COVID-19 can be prevented using appropriate treatments, effective interventions require a thorough research of the genetic factors involved in its pathogenesis.</p><p><strong>Methods: </strong>We conducted a genome-wide association study (GWAS) on 7,124 individuals (comprising 6,400 controls who had mild to moderate COVID-19 and 724 cases with severe COVID-19). The inclusion criteria were acute respiratory distress syndrome (ARDS), acute respiratory failure (ARF) requiring respiratory support, or CT scans indicative of severe COVID-19 infection without any competing diseases. We also developed a polygenic risk score (PRS) model to identify individuals at high risk.</p><p><strong>Results: </strong>We identified two genome-wide significant loci (<i>P</i>-value <5 × 10<sup>-8</sup>) and one locus with approximately genome-wide significance (<i>P</i>-value = 5.92 × 10<sup>-8</sup>-6.15 × 10<sup>-8</sup>). The most genome-wide significant variants were located in the <i>leucine zipper transcription factor like 1</i> (<i>LZTFL1</i>) gene, which has been highlighted in several previous GWAS studies. Our PRS model results indicated that individuals in the top 10% group of the PRS had twice the risk of severe course of the disease compared to those at median risk [odds ratio = 2.18 (1.66, 2.86), <i>P</i>-value = 8.9 × 10<sup>-9</sup>].</p><p><strong>Conclusion: </strong>We conducted one of the largest studies to date on the genetics of severe COVID-19 in an Eastern European cohort. Our results are consistent with previous research and will guide further epidemiologic studies on host genetics, as well as for the development of targeted treatments.</p>\",\"PeriodicalId\":12488,\"journal\":{\"name\":\"Frontiers in Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446758/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fmed.2024.1409714\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fmed.2024.1409714","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
GWAS and polygenic risk score of severe COVID-19 in Eastern Europe.
Background: COVID-19 disease has infected more than 772 million people, leading to 7 million deaths. Although the severe course of COVID-19 can be prevented using appropriate treatments, effective interventions require a thorough research of the genetic factors involved in its pathogenesis.
Methods: We conducted a genome-wide association study (GWAS) on 7,124 individuals (comprising 6,400 controls who had mild to moderate COVID-19 and 724 cases with severe COVID-19). The inclusion criteria were acute respiratory distress syndrome (ARDS), acute respiratory failure (ARF) requiring respiratory support, or CT scans indicative of severe COVID-19 infection without any competing diseases. We also developed a polygenic risk score (PRS) model to identify individuals at high risk.
Results: We identified two genome-wide significant loci (P-value <5 × 10-8) and one locus with approximately genome-wide significance (P-value = 5.92 × 10-8-6.15 × 10-8). The most genome-wide significant variants were located in the leucine zipper transcription factor like 1 (LZTFL1) gene, which has been highlighted in several previous GWAS studies. Our PRS model results indicated that individuals in the top 10% group of the PRS had twice the risk of severe course of the disease compared to those at median risk [odds ratio = 2.18 (1.66, 2.86), P-value = 8.9 × 10-9].
Conclusion: We conducted one of the largest studies to date on the genetics of severe COVID-19 in an Eastern European cohort. Our results are consistent with previous research and will guide further epidemiologic studies on host genetics, as well as for the development of targeted treatments.
期刊介绍:
Frontiers in Medicine publishes rigorously peer-reviewed research linking basic research to clinical practice and patient care, as well as translating scientific advances into new therapies and diagnostic tools. Led by an outstanding Editorial Board of international experts, this multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
In addition to papers that provide a link between basic research and clinical practice, a particular emphasis is given to studies that are directly relevant to patient care. In this spirit, the journal publishes the latest research results and medical knowledge that facilitate the translation of scientific advances into new therapies or diagnostic tools. The full listing of the Specialty Sections represented by Frontiers in Medicine is as listed below. As well as the established medical disciplines, Frontiers in Medicine is launching new sections that together will facilitate
- the use of patient-reported outcomes under real world conditions
- the exploitation of big data and the use of novel information and communication tools in the assessment of new medicines
- the scientific bases for guidelines and decisions from regulatory authorities
- access to medicinal products and medical devices worldwide
- addressing the grand health challenges around the world