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
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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 |
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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