Chintan K Gandhi, Lynnlee C Depicolzuane, Chixiang Chen, Catherine M Roberts, Natalie Sicher, Katelyn Johnson Wegerson, Neal J Thomas, Rongling Wu, Joanna Floros
{"title":"表面活性物质蛋白基因的 SNP-SNP 相互作用与儿童呼吸道合胞病毒感染严重程度的关系。","authors":"Chintan K Gandhi, Lynnlee C Depicolzuane, Chixiang Chen, Catherine M Roberts, Natalie Sicher, Katelyn Johnson Wegerson, Neal J Thomas, Rongling Wu, Joanna Floros","doi":"10.1152/physiolgenomics.00045.2024","DOIUrl":null,"url":null,"abstract":"<p><p>The severity of respiratory syncytial virus (RSV) may be linked to host genetic susceptibility. Surfactant protein (SP) genetic variants have been associated with RSV severity, but the impact of single-nucleotide polymorphism (SNP)-SNP interactions remains unexplored. Therefore, we used a novel statistical model to investigate the association of SNP-SNP interactions of <i>SFTP</i> genes with RSV severity in two- and three-interaction models. We analyzed available genotype and clinical data from prospectively enrolled 405 children diagnosed with RSV, categorizing them into moderate or severe RSV groups. Using Wang's statistical model, we studied significant associations of SNP-SNP interactions with RSV severity in a case-control design. We observed, first, association of three interactions with increased risk of severe RSV in a two-SNP model. One intragenic interaction was between SNPs of <i>SFTPA2</i>, and the other two were intergenic, involving SNPs of hydrophilic and hydrophobic SPs alone. We also observed, second, association of 22 interactions with RSV severity in a three-SNP model. Among these, 20 were unique, with 12 and 10 interactions associated with increased or decreased risk of RSV severity, respectively, and included at least one SNP of either <i>SFTPA1</i> or <i>SFTPA2</i>. All interactions were intergenic except one, among SNPs of <i>SFTPA1</i>. The remaining interactions were either among SNPs of hydrophilic SPs alone (<i>n</i> = 8) or among SNPs of both hydrophilic or hydrophobic SPs (<i>n</i> = 11). Our findings indicate that SNPs of all <i>SFTP</i>s may contribute to genetic susceptibility to RSV severity. However, the predominant involvement of <i>SFTPA1</i> and/or <i>SFTPA2</i> SNPs in these interactions underscores their significance in RSV severity.<b>NEW & NOTEWORTHY</b> Although surfactant protein (SP) genetic variants are associated with respiratory syncytial virus (RSV) severity, the impact of single-nucleotide polymorphism (SNP)-SNP interactions of SP genes remained unexplored. Using advanced statistical models, we uncovered 22 SNP-SNP interactions associated with RSV severity, with notable involvement of <i>SFTPA1</i> and <i>SFTPA2</i> SNPs. This highlights the comprehensive role of all SPs in genetic susceptibility to RSV severity, shedding light on potential avenues for targeted interventions.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495184/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association of SNP-SNP interactions of surfactant protein genes with severity of respiratory syncytial virus infection in children.\",\"authors\":\"Chintan K Gandhi, Lynnlee C Depicolzuane, Chixiang Chen, Catherine M Roberts, Natalie Sicher, Katelyn Johnson Wegerson, Neal J Thomas, Rongling Wu, Joanna Floros\",\"doi\":\"10.1152/physiolgenomics.00045.2024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The severity of respiratory syncytial virus (RSV) may be linked to host genetic susceptibility. Surfactant protein (SP) genetic variants have been associated with RSV severity, but the impact of single-nucleotide polymorphism (SNP)-SNP interactions remains unexplored. Therefore, we used a novel statistical model to investigate the association of SNP-SNP interactions of <i>SFTP</i> genes with RSV severity in two- and three-interaction models. We analyzed available genotype and clinical data from prospectively enrolled 405 children diagnosed with RSV, categorizing them into moderate or severe RSV groups. Using Wang's statistical model, we studied significant associations of SNP-SNP interactions with RSV severity in a case-control design. We observed, first, association of three interactions with increased risk of severe RSV in a two-SNP model. One intragenic interaction was between SNPs of <i>SFTPA2</i>, and the other two were intergenic, involving SNPs of hydrophilic and hydrophobic SPs alone. We also observed, second, association of 22 interactions with RSV severity in a three-SNP model. Among these, 20 were unique, with 12 and 10 interactions associated with increased or decreased risk of RSV severity, respectively, and included at least one SNP of either <i>SFTPA1</i> or <i>SFTPA2</i>. All interactions were intergenic except one, among SNPs of <i>SFTPA1</i>. The remaining interactions were either among SNPs of hydrophilic SPs alone (<i>n</i> = 8) or among SNPs of both hydrophilic or hydrophobic SPs (<i>n</i> = 11). Our findings indicate that SNPs of all <i>SFTP</i>s may contribute to genetic susceptibility to RSV severity. However, the predominant involvement of <i>SFTPA1</i> and/or <i>SFTPA2</i> SNPs in these interactions underscores their significance in RSV severity.<b>NEW & NOTEWORTHY</b> Although surfactant protein (SP) genetic variants are associated with respiratory syncytial virus (RSV) severity, the impact of single-nucleotide polymorphism (SNP)-SNP interactions of SP genes remained unexplored. Using advanced statistical models, we uncovered 22 SNP-SNP interactions associated with RSV severity, with notable involvement of <i>SFTPA1</i> and <i>SFTPA2</i> SNPs. 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Association of SNP-SNP interactions of surfactant protein genes with severity of respiratory syncytial virus infection in children.
The severity of respiratory syncytial virus (RSV) may be linked to host genetic susceptibility. Surfactant protein (SP) genetic variants have been associated with RSV severity, but the impact of single-nucleotide polymorphism (SNP)-SNP interactions remains unexplored. Therefore, we used a novel statistical model to investigate the association of SNP-SNP interactions of SFTP genes with RSV severity in two- and three-interaction models. We analyzed available genotype and clinical data from prospectively enrolled 405 children diagnosed with RSV, categorizing them into moderate or severe RSV groups. Using Wang's statistical model, we studied significant associations of SNP-SNP interactions with RSV severity in a case-control design. We observed, first, association of three interactions with increased risk of severe RSV in a two-SNP model. One intragenic interaction was between SNPs of SFTPA2, and the other two were intergenic, involving SNPs of hydrophilic and hydrophobic SPs alone. We also observed, second, association of 22 interactions with RSV severity in a three-SNP model. Among these, 20 were unique, with 12 and 10 interactions associated with increased or decreased risk of RSV severity, respectively, and included at least one SNP of either SFTPA1 or SFTPA2. All interactions were intergenic except one, among SNPs of SFTPA1. The remaining interactions were either among SNPs of hydrophilic SPs alone (n = 8) or among SNPs of both hydrophilic or hydrophobic SPs (n = 11). Our findings indicate that SNPs of all SFTPs may contribute to genetic susceptibility to RSV severity. However, the predominant involvement of SFTPA1 and/or SFTPA2 SNPs in these interactions underscores their significance in RSV severity.NEW & NOTEWORTHY Although surfactant protein (SP) genetic variants are associated with respiratory syncytial virus (RSV) severity, the impact of single-nucleotide polymorphism (SNP)-SNP interactions of SP genes remained unexplored. Using advanced statistical models, we uncovered 22 SNP-SNP interactions associated with RSV severity, with notable involvement of SFTPA1 and SFTPA2 SNPs. This highlights the comprehensive role of all SPs in genetic susceptibility to RSV severity, shedding light on potential avenues for targeted interventions.
期刊介绍:
The Physiological Genomics publishes original papers, reviews and rapid reports in a wide area of research focused on uncovering the links between genes and physiology at all levels of biological organization. Articles on topics ranging from single genes to the whole genome and their links to the physiology of humans, any model organism, organ, tissue or cell are welcome. Areas of interest include complex polygenic traits preferably of importance to human health and gene-function relationships of disease processes. Specifically, the Journal has dedicated Sections focused on genome-wide association studies (GWAS) to function, cardiovascular, renal, metabolic and neurological systems, exercise physiology, pharmacogenomics, clinical, translational and genomics for precision medicine, comparative and statistical genomics and databases. For further details on research themes covered within these Sections, please refer to the descriptions given under each Section.