In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease
West Nile virus (WNV) is a mosquito-borne virus which causes symptomatic disease in a minority of infected humans. To identify novel genetic variants associated with severe disease, we utilized data from an existing case-control study of WNV and included population controls for an expanded analysis....
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/4/744 |
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| author | Megan E. Cahill Mark Loeb Andrew T. Dewan Ruth R. Montgomery |
| author_facet | Megan E. Cahill Mark Loeb Andrew T. Dewan Ruth R. Montgomery |
| author_sort | Megan E. Cahill |
| collection | DOAJ |
| description | West Nile virus (WNV) is a mosquito-borne virus which causes symptomatic disease in a minority of infected humans. To identify novel genetic variants associated with severe disease, we utilized data from an existing case-control study of WNV and included population controls for an expanded analysis. We conducted imputation and gene-gene interaction analysis in the largest and most comprehensive genetic study conducted to date for West Nile neuroinvasive disease (WNND). Within the imputed West Nile virus dataset (severe cases n = 381 and asymptomatic/mild controls = 441), we found novel loci within the MCF.2 Cell Line Derived Transforming Sequence Like (<i>MCF2L</i>) gene (rs9549655 and rs2297192) through the individual loci analyses, although none reached statistical significance. Incorporating population controls from the Wisconsin Longitudinal Study on Aging (n = 9012) did not identify additional novel variants, a possible reflection of the cohort’s inclusion of individuals who could develop mild or severe WNV disease upon infection. Many of the top gene-gene interaction results were intergenic, with currently undefined biological roles, highlighting the need for further investigation into these regions and other identified gene targets in severe WNND. Further studies including larger sample sizes and more diverse populations reflective of those at risk are needed to fully understand the genetic architecture of severe WNDD and provide guidance on viable targets for therapeutic and vaccine development. |
| first_indexed | 2024-03-10T14:14:56Z |
| format | Article |
| id | doaj.art-b9a752db1a534ceb8a8b88e4d79be124 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T14:14:56Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-b9a752db1a534ceb8a8b88e4d79be1242023-11-20T23:56:16ZengMDPI AGVaccines2076-393X2020-12-018474410.3390/vaccines8040744In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral DiseaseMegan E. Cahill0Mark Loeb1Andrew T. Dewan2Ruth R. Montgomery3Center for Perinatal, Pediatric and Environmental Epidemiology, Department of Chronic Disease Epidemiology, Yale School of Public Health, 1 Church Street, New Haven, CT 06510, USA3208 Michael DeGroote Centre for Learning & Discovery, Division of Clinical Pathology, McMaster University, Hamilton, ON L8S 4L8, CanadaCenter for Perinatal, Pediatric and Environmental Epidemiology, Department of Chronic Disease Epidemiology, Yale School of Public Health, 1 Church Street, New Haven, CT 06510, USADepartment of Internal Medicine, Yale School of Medicine, 300 Cedar Street, New Haven, CT 06520, USAWest Nile virus (WNV) is a mosquito-borne virus which causes symptomatic disease in a minority of infected humans. To identify novel genetic variants associated with severe disease, we utilized data from an existing case-control study of WNV and included population controls for an expanded analysis. We conducted imputation and gene-gene interaction analysis in the largest and most comprehensive genetic study conducted to date for West Nile neuroinvasive disease (WNND). Within the imputed West Nile virus dataset (severe cases n = 381 and asymptomatic/mild controls = 441), we found novel loci within the MCF.2 Cell Line Derived Transforming Sequence Like (<i>MCF2L</i>) gene (rs9549655 and rs2297192) through the individual loci analyses, although none reached statistical significance. Incorporating population controls from the Wisconsin Longitudinal Study on Aging (n = 9012) did not identify additional novel variants, a possible reflection of the cohort’s inclusion of individuals who could develop mild or severe WNV disease upon infection. Many of the top gene-gene interaction results were intergenic, with currently undefined biological roles, highlighting the need for further investigation into these regions and other identified gene targets in severe WNND. Further studies including larger sample sizes and more diverse populations reflective of those at risk are needed to fully understand the genetic architecture of severe WNDD and provide guidance on viable targets for therapeutic and vaccine development.https://www.mdpi.com/2076-393X/8/4/744West Nile virusWest Nile neuroinvasive diseasegenome-wide association studygene-gene interactionsdisease severity |
| spellingShingle | Megan E. Cahill Mark Loeb Andrew T. Dewan Ruth R. Montgomery In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease Vaccines West Nile virus West Nile neuroinvasive disease genome-wide association study gene-gene interactions disease severity |
| title | In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease |
| title_full | In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease |
| title_fullStr | In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease |
| title_full_unstemmed | In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease |
| title_short | In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease |
| title_sort | in depth analysis of genetic variation associated with severe west nile viral disease |
| topic | West Nile virus West Nile neuroinvasive disease genome-wide association study gene-gene interactions disease severity |
| url | https://www.mdpi.com/2076-393X/8/4/744 |
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