In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. WNV-Infected Study Population
2.2. Quality Control and Imputation
2.3. Population Controls
2.4. Analysis of Gene-Gene Interactions
3. Results
3.1. Imputation Increases Identification of Genes Associated with WNV
3.2. Population Controls Extend Univariate Analysis
3.3. Gene-Gene Interactions Identify Combined Effects of Variation at Two Loci of Interest
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Data Availability
Research Involving Human Subjects
References
- World Health Organization. Global Vector Control Response 2017–2030; WHO: Geneva, Switzerland, 2017; p. 41. [Google Scholar]
- World Health Organization. West Nile Virus. Available online: http://www.who.int/news-room/fact-sheets/detail/west-nile-virus (accessed on 23 June 2018).
- GIDEON. “West Nile Fever”—Staying in Real Time. Available online: https://www.gideononline.com/cases/westnilefever/ (accessed on 22 June 2018).
- Centers for Disease Control and Prevention. West Nile Virus. Available online: https://www.cdc.gov/westnile/index.html (accessed on 13 October 2020).
- Huhn, G.D.; Sejvar, J.J.; Montgomery, S.P.; Dworkin, M.S. West Nile virus in the United States: An update on an emerging infectious disease. Am. Fam. Physician 2003, 68, 653–660. [Google Scholar]
- Cahill, M.E.; Yao, Y.; Nock, D.; Armstrong, P.M.; Andreadis, T.G.; Diuk-Wasser, M.A.; Montgomery, R.R. West Nile Virus Seroprevalence, Connecticut, USA, 2000–2014. Emerg. Infect. Dis. 2017, 23, 708–710. [Google Scholar] [CrossRef] [Green Version]
- Montgomery, R.R.; Murray, K.O. Risk factors for West Nile virus infection and disease in populations and individuals. Expert Rev. Anti Infect. Ther. 2015, 13, 317–325. [Google Scholar] [CrossRef] [Green Version]
- Yeung, M.W.; Shing, E.; Nelder, M.; Sander, B. Epidemiologic and clinical parameters of West Nile virus infections in humans: A scoping review. BMC Infect. Dis. 2017, 17, 609. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bai, F.; Thompson, E.A.; Vig, P.J.S.; Leis, A.A. Current Understanding of West Nile Virus Clinical Manifestations, Immune Responses, Neuroinvasion, and Immunotherapeutic Implications. Pathogens 2019, 8, 193. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cahill, M.E.; Conley, S.; DeWan, A.T.; Montgomery, R.R. Identification of genetic variants associated with dengue or West Nile virus disease: A systematic review and meta-analysis. BMC Infect. Dis. 2018, 18, 282. [Google Scholar] [CrossRef] [PubMed]
- Loeb, M.; Eskandarian, S.; Rupp, M.; Fishman, N.; Gasink, L.; Patterson, J.; Bramson, J.; Hudson, T.J.; Lemire, M. Genetic variants and susceptibility to neurological complications following West Nile virus infection. J. Infect. Dis. 2011, 204, 1031–1037. [Google Scholar] [CrossRef]
- Kenney, A.D.; Dowdle, J.A.; Bozzacco, L.; McMichael, T.M.; St Gelais, C.; Panfil, A.R.; Sun, Y.; Schlesinger, L.S.; Anderson, M.Z.; Green, P.L.; et al. Human Genetic Determinants of Viral Diseases. Annu. Rev. Genet. 2017, 51, 241–263. [Google Scholar] [CrossRef] [PubMed]
- Mozzi, A.; Pontremoli, C.; Sironi, M. Genetic susceptibility to infectious diseases: Current status and future perspectives from genome-wide approaches. Infect. Genet. Evol. 2018, 66, 286–307. [Google Scholar] [CrossRef] [PubMed]
- Gibson, G. Rare and common variants: Twenty arguments. Nat. Rev. Genet. 2012, 13, 135–145. [Google Scholar] [CrossRef] [Green Version]
- Ulbert, S. West Nile virus vaccines-current situation and future directions. Hum. Vaccin. Immunother. 2019, 15, 2337–2342. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Purcell, S.; Neale, B.; Todd-Brown, K.; Thomas, L.; Ferreira, M.A.; Bender, D.; Maller, J.; Sklar, P.; de Bakker, P.I.; Daly, M.J.; et al. PLINK: A tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 2007, 81, 559–575. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kent, W.J.; Sugnet, C.W.; Furey, T.S.; Roskin, K.M.; Pringle, T.H.; Zahler, A.M.; Haussler, D. The human genome browser at UCSC. Genome. Res. 2002, 12, 996–1006. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Howie, B.N.; Donnelly, P.; Marchini, J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 2009, 5, e1000529. [Google Scholar] [CrossRef] [Green Version]
- Delaneau, O.; Marchini, J.; Zagury, J.F. A linear complexity phasing method for thousands of genomes. Nat. Methods 2011, 9, 179–181. [Google Scholar] [CrossRef]
- The 1000 Genomes Project Consortium; Auton, A.; Brooks, L.D.; Durbin, R.M.; Garrison, E.P.; Kang, H.M.; Korbel, J.O.; Marchini, J.L.; McCarthy, S.; McVean, G.A.; et al. A global reference for human genetic variation. Nature 2015, 526, 68–74. [Google Scholar] [CrossRef] [Green Version]
- Patterson, N.; Price, A.L.; Reich, D. Population structure and eigenanalysis. PLoS Genet. 2006, 2, e190. [Google Scholar] [CrossRef]
- Price, A.L.; Patterson, N.J.; Plenge, R.M.; Weinblatt, M.E.; Shadick, N.A.; Reich, D. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 2006, 38, 904–909. [Google Scholar] [CrossRef]
- Risch, N.; Merikangas, K. The future of genetic studies of complex human diseases. Science 1996, 273, 1516–1517. [Google Scholar] [CrossRef] [Green Version]
- Bonferroni, C. Il Calcolo Delle Assicurazioni su Gruppi di Teste. In Studi in Onore del Professore Salvatore Ortu Carboni; ScienceOpen: Rome, Italy, 1935; pp. 13–60. [Google Scholar]
- Turner, S.D. qqman: An R package for visualizing GWAS results using Q-Q and manhattan plots. biorXiv 2014. [Google Scholar] [CrossRef]
- Gonzales, T.K.; Yonker, J.A.; Chang, V.; Roan, C.L.; Herd, P.; Atwood, C.S. Myocardial infarction in the Wisconsin Longitudinal Study: The interaction among environmental, health, social, behavioural and genetic factors. BMJ Open 2017, 7, e011529. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Herd, P.; Carr, D.; Roan, C. Cohort profile: Wisconsin longitudinal study (WLS). Int. J. Epidemiol. 2014, 43, 34–41. [Google Scholar] [CrossRef] [PubMed]
- Tryka, K.A.; Hao, L.; Sturcke, A.; Jin, Y.; Wang, Z.Y.; Ziyabari, L.; Lee, M.; Popova, N.; Sharopova, N.; Kimura, M.; et al. NCBI’s Database of Genotypes and Phenotypes: dbGaP. Nucleic. Acids Res. 2014, 42, 975–979. [Google Scholar] [CrossRef] [PubMed]
- Herd, P. Wisconsin Longitudinal Study. Available online: https://www.ssc.wisc.edu/wlsresearch/ (accessed on 30 December 2018).
- Wisconsin Longitudinal Study. A Longitudinal Resource for Genetic Research in Behavioral and Health Sciences: Imputation Report, 1000 Genomes Project Reference Panel (Phase 3). Available online: https://www.ssc.wisc.edu/wlsresearch/documentation/GWAS/Herd_1000G_IMPUTE2report.pdf (accessed on 2 November 2016).
- Patterson, N.; Price, A.L.; Reich, D. EIGENSOFT, 6.1.4. Available online: https://github.com/DReichLab/EIG (accessed on 3 March 2019).
- Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases. Clinical Evaluation & Disease. Available online: https://www.cdc.gov/westnile/healthcareproviders/healthCareProviders-ClinLabEval.html (accessed on 13 October 2020).
- Lazear, H.M.; Diamond, M.S. New insights into innate immune restriction of West Nile virus infection. Curr. Opin. Virol. 2015, 11, 1–6. [Google Scholar] [CrossRef] [Green Version]
- Netland, J.; Bevan, M.J. CD8 and CD4 T cells in west nile virus immunity and pathogenesis. Viruses 2013, 5, 2573–2584. [Google Scholar] [CrossRef]
- Glass, W.G.; McDermott, D.H.; Lim, J.K.; Lekhong, S.; Yu, S.F.; Frank, W.A.; Pape, J.; Cheshier, R.C.; Murphy, P.M. CCR5 deficiency increases risk of symptomatic West Nile virus infection. J. Exp. Med. 2006, 203, 35–40. [Google Scholar] [CrossRef] [Green Version]
- Bigham, A.W.; Buckingham, K.J.; Husain, S.; Emond, M.J.; Bofferding, K.M.; Gildersleeve, H.; Rutherford, A.; Astakhova, N.M.; Perelygin, A.A.; Busch, M.P.; et al. Host genetic risk factors for West Nile virus infection and disease progression. PLoS ONE 2011, 6, e24745. [Google Scholar] [CrossRef]
- Das, R.; Loughran, K.; Murchison, C.; Qian, F.; Leng, L.; Song, Y.; Montgomery, R.R.; Loeb, M.; Bucala, R. Association between high expression macrophage migration inhibitory factor (MIF) alleles and West Nile virus encephalitis. Cytokine 2016, 78, 51–54. [Google Scholar] [CrossRef] [Green Version]
- Danial-Farran, N.; Eghbaria, S.; Schwartz, N.; Kra-Oz, Z.; Bisharat, N. Genetic variants associated with susceptibility of Ashkenazi Jews to West Nile virus infection. Epidemiol. Infect. 2015, 143, 857–863. [Google Scholar] [CrossRef]
- Lim, J.K.; Lisco, A.; McDermott, D.H.; Huynh, L.; Ward, J.M.; Johnson, B.; Johnson, H.; Pape, J.; Foster, G.A.; Krysztof, D.; et al. Genetic variation in OAS1 is a risk factor for initial infection with West Nile virus in man. PLoS Pathog. 2009, 5, e1000321. [Google Scholar] [CrossRef]
- Yakub, I.; Lillibridge, K.M.; Moran, A.; Gonzalez, O.Y.; Belmont, J.; Gibbs, R.A.; Tweardy, D.J. Single nucleotide polymorphisms in genes for 2′-5′-oligoadenylate synthetase and RNase L inpatients hospitalized with West Nile virus infection. J. Infect. Dis. 2005, 192, 1741–1748. [Google Scholar] [CrossRef] [PubMed]
- Van den Broeke, C.; Jacob, T.; Favoreel, H.W. Rho’ing in and out of cells: Viral interactions with Rho GTPase signaling. Small GTPases 2014, 5, e28318. [Google Scholar] [CrossRef] [PubMed]
- Fraisier, C.; Camoin, L.; Lim, S.M.; Bakli, M.; Belghazi, M.; Fourquet, P.; Granjeaud, S.; Osterhaus, A.D.; Koraka, P.; Martina, B.; et al. Altered protein networks and cellular pathways in severe west nile disease in mice. PLoS ONE 2013, 8, e68318. [Google Scholar] [CrossRef]
- Foo, K.Y.; Chee, H.Y. Interaction between Flavivirus and Cytoskeleton during Virus Replication. Biomed Res. Int. 2015, 2015, 427814. [Google Scholar] [CrossRef] [Green Version]
- Moni, M.A.; Lio, P. Genetic Profiling and Comorbidities of Zika Infection. J. Infect. Dis. 2017, 216, 703–712. [Google Scholar] [CrossRef]
- Hau, P.M.; Tsao, S.W. Epstein-Barr Virus Hijacks DNA Damage Response Transducers to Orchestrate Its Life Cycle. Viruses 2017, 9, 341. [Google Scholar] [CrossRef] [Green Version]
- Dheekollu, J.; Lieberman, P.M. The replisome pausing factor Timeless is required for episomal maintenance of latent Epstein-Barr virus. J. Virol. 2011, 85, 5853–5863. [Google Scholar] [CrossRef] [Green Version]
- Qian, F.; Chung, L.; Zheng, W.; Bruno, V.; Alexander, R.P.; Wang, Z.; Wang, X.; Kurscheid, S.; Zhao, H.; Fikrig, E.; et al. Identification of genes critical for resistance to infection by West Nile virus using RNA-Seq analysis. Viruses 2013, 5, 1664–1681. [Google Scholar] [CrossRef]
- Qian, F.; Goel, G.; Meng, H.; Wang, X.; You, F.; Devine, L.; Raddassi, K.; Garcia, M.N.; Murray, K.O.; Bolen, C.R.; et al. Systems immunology reveals markers of susceptibility to West Nile virus infection. Clin. Vaccine Immunol. 2015, 22, 6–16. [Google Scholar] [CrossRef] [Green Version]
- Qian, F.; Thakar, J.; Yuan, X.; Nolan, M.; Murray, K.O.; Lee, W.T.; Wong, S.J.; Meng, H.; Fikrig, E.; Kleinstein, S.H.; et al. Immune markers associated with host susceptibility to infection with West Nile virus. Viral Immunol. 2014, 27, 39–47. [Google Scholar] [CrossRef] [Green Version]
- McGuckin Wuertz, K.; Treuting, P.M.; Hemann, E.A.; Esser-Nobis, K.; Snyder, A.G.; Graham, J.B.; Daniels, B.P.; Wilkins, C.; Snyder, J.M.; Voss, K.M.; et al. STING is required for host defense against neuropathological West Nile virus infection. PLoS Pathog. 2019, 15, e1007899. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zimmerman, M.G.; Bowen, J.R.; McDonald, C.E.; Pulendran, B.; Suthar, M.S. West Nile Virus Infection Blocks Inflammatory Response and T Cell Costimulatory Capacity of Human Monocyte-Derived Dendritic Cells. J. Virol. 2019, 93. [Google Scholar] [CrossRef]
- Mitchell, B.D.; Fornage, M.; McArdle, P.F.; Cheng, Y.C.; Pulit, S.L.; Wong, Q.; Dave, T.; Williams, S.R.; Corriveau, R.; Gwinn, K.; et al. Using previously genotyped controls in genome-wide association studies (GWAS): Application to the Stroke Genetics Network (SiGN). Front. Genet. 2014, 5, 95. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases. West Nile Virus Disease Cases and Deaths Reported to CDC by Year and Clinical Presentation, 1999–2018. Available online: https://www.cdc.gov/westnile/statsmaps/cumMapsData.html (accessed on 29 September 2020).
- Chancey, C.; Grinev, A.; Volkova, E.; Rios, M. The global ecology and epidemiology of West Nile virus. Biomed Res. Int. 2015, 2015, 376230. [Google Scholar] [CrossRef] [Green Version]
- Gene, National Center for Biotechnology Information, USA National Library of Medicine. HS3ST4 Heparan Sulfate-Glucosamine 3-Sulfotransferase 4 [Homo Sapiens (Human)]. Available online: https://www.ncbi.nlm.nih.gov/gene?term=9951 (accessed on 1 October 2020).
- Denys, A.; Allain, F. The Emerging Roles of Heparan Sulfate 3-O-Sulfotransferases in Cancer. Front. Oncol. 2019, 9, 507. [Google Scholar] [CrossRef] [Green Version]
- Biroccio, A.; Cherfils-Vicini, J.; Augereau, A.; Pinte, S.; Bauwens, S.; Ye, J.; Simonet, T.; Horard, B.; Jamet, K.; Cervera, L.; et al. TRF2 inhibits a cell-extrinsic pathway through which natural killer cells eliminate cancer cells. Nat. Cell Biol. 2013, 15, 818–828. [Google Scholar] [CrossRef]
- Yao, Y.; Strauss-Albee, D.M.; Zhou, J.Q.; Malawista, A.; Garcia, M.N.; Murray, K.O.; Blish, C.A.; Montgomery, R.R. The natural killer cell response to West Nile virus in young and old individuals with or without a prior history of infection. PLoS ONE 2017, 12, e0172625. [Google Scholar] [CrossRef]
- Wang, T.; Welte, T. Role of natural killer and Gamma-delta T cells in West Nile virus infection. Viruses 2013, 5, 2298–2310. [Google Scholar] [CrossRef] [Green Version]
- Luu, P.-L.; Ong, P.-T.; Dinh, T.-P.; Clark, S.J. Benchmark study comparing liftover tools for genome conversion of epigenome sequencing data. NAR Genom. Bioinform. 2020, 2. [Google Scholar] [CrossRef]
- Pan, B.; Kusko, R.; Xiao, W.; Zheng, Y.; Liu, Z.; Xiao, C.; Sakkiah, S.; Guo, W.; Gong, P.; Zhang, C.; et al. Correction to: Similarities and differences between variants called with human reference genome HG19 or HG38. BMC Bioinform. 2019, 20, 252. [Google Scholar] [CrossRef]
- Browning, B.L.; Browning, S.R. Genotype Imputation with Millions of Reference Samples. Am. J. Hum. Genet. 2016, 98, 116–126. [Google Scholar] [CrossRef] [Green Version]
- Shi, S.; Yuan, N.; Yang, M.; Du, Z.; Wang, J.; Sheng, X.; Wu, J.; Xiao, J. Comprehensive Assessment of Genotype Imputation Performance. Hum. Hered. 2018, 83, 107–116. [Google Scholar] [CrossRef] [PubMed]
- Brinster, R.; Kottgen, A.; Tayo, B.O.; Schumacher, M.; Sekula, P.; Consortium, C.K. Control procedures and estimators of the false discovery rate and their application in low-dimensional settings: An empirical investigation. BMC Bioinform. 2018, 19, 78. [Google Scholar] [CrossRef] [PubMed]
- Fadista, J.; Manning, A.K.; Florez, J.C.; Groop, L. The (in)famous GWAS P-value threshold revisited and updated for low-frequency variants. Eur. J. Hum. Genet. 2016, 24, 1202–1205. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Panagiotou, O.A.; Ioannidis, J.P.; Genome-Wide Significance, P. What should the genome-wide significance threshold be? Empirical replication of borderline genetic associations. Int. J. Epidemiol. 2012, 41, 273–286. [Google Scholar] [CrossRef] [PubMed]
- Xu, C.; Tachmazidou, I.; Walter, K.; Ciampi, A.; Zeggini, E.; Greenwood, C.M.; Consortium, U.K. Estimating genome-wide significance for whole-genome sequencing studies. Genet. Epidemiol. 2014, 38, 281–290. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Haralambieva, I.H.; Ovsyannikova, I.G.; Pankratz, V.S.; Kennedy, R.B.; Jacobson, R.M.; Poland, G.A. The genetic basis for interindividual immune response variation to measles vaccine: New understanding and new vaccine approaches. Expert Rev. Vaccines 2013, 12, 57–70. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mentzer, A.J.; O’Connor, D.; Pollard, A.J.; Hill, A.V. Searching for the human genetic factors standing in the way of universally effective vaccines. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2015, 370. [Google Scholar] [CrossRef]
- Noll, K.E.; Whitmore, A.C.; West, A.; McCarthy, M.K.; Morrison, C.R.; Plante, K.S.; Hampton, B.K.; Kollmus, H.; Pilzner, C.; Leist, S.R.; et al. Complex Genetic Architecture Underlies Regulation of Influenza-A-Virus-Specific Antibody Responses in the Collaborative Cross. Cell Rep. 2020, 31, 107587. [Google Scholar] [CrossRef]
- Johnson, J.L. Genetic Association Study (GAS) Power Calculator; University of Michigan School of Public Health: Ann Arbor, MI, USA, 2017. [Google Scholar]
- National Center for Biotechnology Information, USA. National Library of Medicine. Wisconsin Longitudinal Study on Aging. dbGaP Study Accession: phs001157.v1.p1. Available online: https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001157.v1.p1 (accessed on 1 September 2020).
Chr | SNP | Gene | Base Position | OR | p-Value |
---|---|---|---|---|---|
13 | rs9549655 | MCF2L | 113725367 | 2.38 | 5.84 × 10−7 |
4 | rs3065938 | Intergenic | 125374129 | 0.36 | 9.45 × 10−7 |
13 | rs2297192 | MCF2L | 113720476 | 2.23 | 1.35 × 10−6 |
8 | rs78660320 | TEX15 | 30739132 | 0.44 | 1.76 × 10−6 |
13 | rs701542 | Intergenic | 103581620 | 2.30 | 2.05 × 10−6 |
15 | rs36061431 | TIPIN | 66669445 | 2.27 | 2.43 × 10−6 |
1 | rs7553671 | KCNN3 | 154737236 | 0.48 | 2.49 × 10−6 |
6 | rs4706217 | Intergenic | 85705226 | 0.48 | 2.79 × 10−6 |
13 | rs783448 | Intergenic | 103581492 | 2.29 | 2.89 × 10−6 |
13 | rs783449 | Intergenic | 103581457 | 2.15 | 3.92 × 10−6 |
Chr | SNP | Gene | OR | p-Value from Population Control Analysis | p-Value from WNV-Only Analysis | WNV Cases MAF | WNV Controls MAF | Population Controls MAF |
---|---|---|---|---|---|---|---|---|
13 | rs2297192 | MCF2L | 2.13 | 2.30 × 10−6 | 1.35 × 10−6 | 0.203 | 0.127 | 0.167 |
3 | rs9834139 | Intergenic | 1.91 | 1.13 × 10−5 | 5.60 × 10−5 | 0.381 | 0.288 | 0.337 |
1 | rs1245487 | LOC105378861 | 1.84 | 3.48 × 10−5 | 2.28 × 10−5 | 0.357 | 0.291 | 0.317 |
12 | rs10850475 | Intergenic | 0.54 | 5.74 × 10−5 | 1.10 × 10−4 | 0.144 | 0.217 | 0.191 |
1 | rs10489329 | Intergenic | 1.78 | 8.06 × 10−5 | 3.44 × 10−4 | 0.327 | 0.225 | 0.257 |
13 | rs3814264 | MCF2L | 1.79 | 9.14 × 10−5 | 2.51 × 10−5 | 0.249 | 0.179 | 0.224 |
11 | rs576598 | Intergenic | 0.56 | 9.23 × 10−5 | 4.88 × 10−5 | 0.302 | 0.379 | 0.341 |
11 | rs694539 | NNMT | 0.54 | 9.71 × 10−5 | 1.47 × 10−4 | 0.133 | 0.206 | 0.183 |
21 | rs2407581 | LOC105372745 | 1.77 | 1.05 × 10−4 | 5.16 × 10−5 | 0.298 | 0.229 | 0.267 |
13 | rs556694 | F10 | 0.48 | 1.08 × 10−4 | 4.93 × 10−4 | 0.073 | 0.137 | 0.106 |
First SNP | Second SNP | p-Value | ||||||
---|---|---|---|---|---|---|---|---|
Chr | SNP | BP | GENE | CH | SNP | BP | GENE | |
9 | rs7021419 | 2322572 | Intergenic | 16 | rs9989408 | 25879109 | HS3ST4 | 2.42 × 10−11 |
9 | rs7021419 | 2322572 | Intergenic | 16 | rs12708686 | 25881959 | HS3ST4 | 6.22 × 10−11 |
3 | rs941304 | 74887781 | LOC 105377167 | 8 | rs3847131 | 32282019 | NRG1 | 2.08 × 10−10 |
5 | rs465962 | 66197511 | MAST4 | 18 | rs1943676 | 47017820 | RPL17 | 3.41 × 10−10 |
5 | rs153411 | 153753481 | GALNT10 | 11 | rs11228306 | 56184659 | OR5R1 | 4.04 × 10−10 |
3 | rs2030874 | 5547942 | Intergenic | 14 | rs17105314 | 37257671 | SLC25A21 | 4.44 × 10−10 |
8 | rs2627359 | 3743017 | CSMD1 | 12 | rs12304940 | 68457881 | LOC 107984526 | 4.53 × 10−10 |
5 | rs154620 | 66200248 | MAST4 | 18 | rs1943676 | 47017820 | RPL17 | 4.57 × 10−10 |
2 | rs4426483 | 155807051 | LOC 105373696 | 3 | rs2568844 | 71288864 | FOXP1 | 5.04 × 10−10 |
11 | rs1425936 | 36399514 | PRR5L | 17 | rs758142 | 55740786 | MSI2 | 6.77 × 10−10 |
16 | rs173839 | 83782302 | CDH13 | 22 | rs2075120 | 17326432 | Intergenic | 7.40 × 10−10 |
7 | rs10464364 | 38652088 | AMPH | 18 | rs4468704 | 37727465 | Intergenic | 8.29 × 10−10 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Cahill, M.E.; Loeb, M.; Dewan, A.T.; Montgomery, R.R. In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease. Vaccines 2020, 8, 744. https://doi.org/10.3390/vaccines8040744
Cahill ME, Loeb M, Dewan AT, Montgomery RR. In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease. Vaccines. 2020; 8(4):744. https://doi.org/10.3390/vaccines8040744
Chicago/Turabian StyleCahill, Megan E., Mark Loeb, Andrew T. Dewan, and Ruth R. Montgomery. 2020. "In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease" Vaccines 8, no. 4: 744. https://doi.org/10.3390/vaccines8040744
APA StyleCahill, M. E., Loeb, M., Dewan, A. T., & Montgomery, R. R. (2020). In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease. Vaccines, 8(4), 744. https://doi.org/10.3390/vaccines8040744