Alexey Loktionov, Ksenia Kobzeva, Anna Dorofeeva, Vera Sergeeva, Olga Bushueva
{"title":"GWAS 确定的基因位点与严重 COVID-19 患者的肥胖和 2 型糖尿病有关。","authors":"Alexey Loktionov, Ksenia Kobzeva, Anna Dorofeeva, Vera Sergeeva, Olga Bushueva","doi":"10.31083/j.fbs1603014","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Comorbidities such as obesity and type 2 diabetes mellitus (T2DM) have emerged as critical risk factors exacerbating the severity and mortality of COVID-19. Meanwhile, numerous genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with increased susceptibility to severe COVID-19.</p><p><strong>Aim: </strong>This study investigated whether SNPs previously identified by GWAS as risk factors for severe COVID-19 also correlate with common comorbidities-obesity and T2DM-in hospitalized patients with severe COVID-19.</p><p><strong>Methods: </strong>DNA samples from 199 hospitalized COVID-19 patients were genotyped using probe-based PCR for 10 GWAS SNPs previously implicated in severe COVID-19 outcomes (rs143334143 <i>CCHCR1</i>, rs111837807 <i>CCHCR1</i>, rs17078346 <i>SLC6A20</i>-<i>LZTFL1</i>, rs17713054 <i>SLC6A20</i>-<i>LZTFL1</i>, rs7949972 <i>ELF5</i>, rs61882275 <i>ELF5</i>, rs12585036 <i>ATP11A</i>, rs67579710 <i>THBS3</i>, <i>THBS3</i>-<i>AS1</i>, rs12610495 <i>DPP9</i>, rs9636867 <i>IFNAR2</i>).</p><p><strong>Results: </strong>The analysis revealed significant associations between certain SNPs and the increased risk of obesity and T2DM in severe COVID-19 patients. Specifically, rs17713054 <i>SLC6A20</i>-<i>LZTFL1</i> (risk allele A; odds ratio (OR) = 2.34, 95% confidence interval (CI) = 1.24-4.4, <i>p</i> = 0.007) and rs7949972 <i>ELF5</i> SNP (risk allele T; OR = 1.79, 95% CI = 1.11-2.91, <i>p</i> = 0.015) were associated with increased risk of obesity. SNP rs9636867 <i>IFNAR2</i> was associated with a higher risk of T2DM (risk allele G, OR = 8.28, 95% CI = 1.69-40.64, <i>p</i> = 0.027). Using the model-based multifactor dimensionality reduction (MB-MDR) approach, the six most significant gene-gene interaction patterns associated with obesity in severe COVID-19 patients were identified and included five polymorphic loci: rs7949972, rs17713054, rs61882275, rs12585036, and rs143334143, participating in two or more of the most significant G-G interactions (<i>pperm</i> < 0.05). In total, the best models of G-G interactions associated with T2DM in patients with severe COVID-19 included eight polymorphic loci, six of which, rs7949972, rs61882275, rs12585036, rs143334143, rs67579710, and rs12610495, were involved in two or more of the most significant G-G interactions.</p><p><strong>Conclusions: </strong>Our study provides novel insights into the genetic associations between GWAS-identified SNPs and the risk of obesity and T2DM in patients with severe COVID-19.</p>","PeriodicalId":73070,"journal":{"name":"Frontiers in bioscience (Scholar edition)","volume":"16 3","pages":"14"},"PeriodicalIF":0.0000,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"GWAS-Identified Loci are Associated with Obesity and Type 2 Diabetes Mellitus in Patients with Severe COVID-19.\",\"authors\":\"Alexey Loktionov, Ksenia Kobzeva, Anna Dorofeeva, Vera Sergeeva, Olga Bushueva\",\"doi\":\"10.31083/j.fbs1603014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Comorbidities such as obesity and type 2 diabetes mellitus (T2DM) have emerged as critical risk factors exacerbating the severity and mortality of COVID-19. Meanwhile, numerous genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with increased susceptibility to severe COVID-19.</p><p><strong>Aim: </strong>This study investigated whether SNPs previously identified by GWAS as risk factors for severe COVID-19 also correlate with common comorbidities-obesity and T2DM-in hospitalized patients with severe COVID-19.</p><p><strong>Methods: </strong>DNA samples from 199 hospitalized COVID-19 patients were genotyped using probe-based PCR for 10 GWAS SNPs previously implicated in severe COVID-19 outcomes (rs143334143 <i>CCHCR1</i>, rs111837807 <i>CCHCR1</i>, rs17078346 <i>SLC6A20</i>-<i>LZTFL1</i>, rs17713054 <i>SLC6A20</i>-<i>LZTFL1</i>, rs7949972 <i>ELF5</i>, rs61882275 <i>ELF5</i>, rs12585036 <i>ATP11A</i>, rs67579710 <i>THBS3</i>, <i>THBS3</i>-<i>AS1</i>, rs12610495 <i>DPP9</i>, rs9636867 <i>IFNAR2</i>).</p><p><strong>Results: </strong>The analysis revealed significant associations between certain SNPs and the increased risk of obesity and T2DM in severe COVID-19 patients. Specifically, rs17713054 <i>SLC6A20</i>-<i>LZTFL1</i> (risk allele A; odds ratio (OR) = 2.34, 95% confidence interval (CI) = 1.24-4.4, <i>p</i> = 0.007) and rs7949972 <i>ELF5</i> SNP (risk allele T; OR = 1.79, 95% CI = 1.11-2.91, <i>p</i> = 0.015) were associated with increased risk of obesity. SNP rs9636867 <i>IFNAR2</i> was associated with a higher risk of T2DM (risk allele G, OR = 8.28, 95% CI = 1.69-40.64, <i>p</i> = 0.027). Using the model-based multifactor dimensionality reduction (MB-MDR) approach, the six most significant gene-gene interaction patterns associated with obesity in severe COVID-19 patients were identified and included five polymorphic loci: rs7949972, rs17713054, rs61882275, rs12585036, and rs143334143, participating in two or more of the most significant G-G interactions (<i>pperm</i> < 0.05). In total, the best models of G-G interactions associated with T2DM in patients with severe COVID-19 included eight polymorphic loci, six of which, rs7949972, rs61882275, rs12585036, rs143334143, rs67579710, and rs12610495, were involved in two or more of the most significant G-G interactions.</p><p><strong>Conclusions: </strong>Our study provides novel insights into the genetic associations between GWAS-identified SNPs and the risk of obesity and T2DM in patients with severe COVID-19.</p>\",\"PeriodicalId\":73070,\"journal\":{\"name\":\"Frontiers in bioscience (Scholar edition)\",\"volume\":\"16 3\",\"pages\":\"14\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in bioscience (Scholar edition)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.31083/j.fbs1603014\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in bioscience (Scholar edition)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.31083/j.fbs1603014","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
GWAS-Identified Loci are Associated with Obesity and Type 2 Diabetes Mellitus in Patients with Severe COVID-19.
Background: Comorbidities such as obesity and type 2 diabetes mellitus (T2DM) have emerged as critical risk factors exacerbating the severity and mortality of COVID-19. Meanwhile, numerous genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with increased susceptibility to severe COVID-19.
Aim: This study investigated whether SNPs previously identified by GWAS as risk factors for severe COVID-19 also correlate with common comorbidities-obesity and T2DM-in hospitalized patients with severe COVID-19.
Methods: DNA samples from 199 hospitalized COVID-19 patients were genotyped using probe-based PCR for 10 GWAS SNPs previously implicated in severe COVID-19 outcomes (rs143334143 CCHCR1, rs111837807 CCHCR1, rs17078346 SLC6A20-LZTFL1, rs17713054 SLC6A20-LZTFL1, rs7949972 ELF5, rs61882275 ELF5, rs12585036 ATP11A, rs67579710 THBS3, THBS3-AS1, rs12610495 DPP9, rs9636867 IFNAR2).
Results: The analysis revealed significant associations between certain SNPs and the increased risk of obesity and T2DM in severe COVID-19 patients. Specifically, rs17713054 SLC6A20-LZTFL1 (risk allele A; odds ratio (OR) = 2.34, 95% confidence interval (CI) = 1.24-4.4, p = 0.007) and rs7949972 ELF5 SNP (risk allele T; OR = 1.79, 95% CI = 1.11-2.91, p = 0.015) were associated with increased risk of obesity. SNP rs9636867 IFNAR2 was associated with a higher risk of T2DM (risk allele G, OR = 8.28, 95% CI = 1.69-40.64, p = 0.027). Using the model-based multifactor dimensionality reduction (MB-MDR) approach, the six most significant gene-gene interaction patterns associated with obesity in severe COVID-19 patients were identified and included five polymorphic loci: rs7949972, rs17713054, rs61882275, rs12585036, and rs143334143, participating in two or more of the most significant G-G interactions (pperm < 0.05). In total, the best models of G-G interactions associated with T2DM in patients with severe COVID-19 included eight polymorphic loci, six of which, rs7949972, rs61882275, rs12585036, rs143334143, rs67579710, and rs12610495, were involved in two or more of the most significant G-G interactions.
Conclusions: Our study provides novel insights into the genetic associations between GWAS-identified SNPs and the risk of obesity and T2DM in patients with severe COVID-19.
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