Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Samples
2.2. Sequencing and Genotyping
2.3. Association and Meta-Association Analysis
2.4. Copy Number Variant Analysis
2.5. Extra Visualization and Downstream Analysis
3. Results
3.1. Study Population
3.2. Induction and Maintenance Immunosuppression Regimen
3.3. CMV DNAemia Variant Association Analysis
3.4. CMV DNAemia Copy Number Association Analysis
3.5. CMV DNAemia Peak Viral Load Association Analysis
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Cohort | A | B | Total |
---|---|---|---|
Participants (%) | 72 (36.3%) | 126 (63.6%) | 198 (100%) |
Male (%) | 41 (56.9%) | 75 (59.5%) | 116 (58.5%) |
CMV DNAemia (%) | 36 (50%) | 60 (47.6%) | 96 (48.4%) |
Caucasian (%) | 54 (75%) | 126 (100%) | 180 (90.9%) |
Age at time of transplant (Mean, SE) | 54.5 (14) | 51.2 (1.4) | 51.2 (1.4) |
Peak viral load (Mean, SE) | 2.4 × 106 (1.4 × 106) | 6.5 × 105 (2.6 × 105) | 1.3 × 106 (5.5 × 106) |
Variant | p-Value | Beta | |||||||
---|---|---|---|---|---|---|---|---|---|
ID | GENE | EFFECT | CADD | Meta | A | B | Z-Meta | A | B |
11_6569896_G_A | DNHD1 | Frameshift, missense | 23.5 | 1.00 × 10−5 | 1.20 × 10−2 | 4.90 × 10−4 | −4.41 | −0.25 | −0.28 |
1_5937391_C_T | NPHP4 | Intron | 0.184 | 2.30 × 10−5 | 5.40 × 10−3 | 1.10 × 10−3 | 4.23 | 0.3 | 0.24 |
19_41119273_G_C | LTBP4 | Intron | 6.661 | 2.80 × 10−5 | 3.20 × 10−3 | 1.70 × 10−3 | −4.19 | −0.26 | −0.24 |
22_45205158_G_GT | PRR5—ARHGAP8 | Intron | 2.397 | 2.80 × 10−5 | N/A | 4.70 × 10−5 | 4.19 | N/A | 0.38 |
6_32557621_T_G | HLA-DRB1 | Upstream | N/A | 4.60 × 10−5 | 4.60 × 10−5 | N/A | 4.07 | 0.51 | N/A |
1_166591271_T_C | FMO9P | Splice donor and intron | 23.2 | 5.20 × 10−5 | 9.60 × 10−3 | 1.30 × 10−3 | 4.05 | 0.34 | 0.25 |
21_27840567_C_T | CYYR1 | 3′ prime UTR | 7.693 | 6.20 × 10−5 | 6.20 × 10−5 | N/A | −4.01 | −0.58 | NA |
8_126085586_G_A | WASHC5 | Intron | 1.184 | 6.40 × 10−5 | 5.90 × 10−3 | 2.70 × 10−3 | −4 | −0.42 | −0.25 |
8_126068873_T_G | WASHC5 | Intron | 0.375 | 8.50 × 10−5 | 2.40 × 10−2 | 1.10 × 10−3 | −3.93 | −0.43 | −0.36 |
10_12195881_G_A | SEC61A2 | Intron | 3.243 | 8.90 × 10−5 | 8.90 × 10−5 | N/A | −3.92 | −0.37 | N/A |
SYMBOL | A_Loss | B_Loss | A_Gain | B_Gain | A | B | Loss | Gain | Overall | FDR |
---|---|---|---|---|---|---|---|---|---|---|
LCE3B | 12 | 16 | 0 | 0 | 12 | 16 | 28 | 0 | 28 | 2.51 × 10−6 |
LCE3C | 13 | 15 | 0 | 0 | 13 | 15 | 28 | 0 | 28 | 2.51 × 10−6 |
TAS2R43 | 5 | 13 | 0 | 0 | 5 | 13 | 18 | 0 | 18 | 1.71 × 10−3 |
GSTM1 | 17 | 0 | 0 | 0 | 17 | 0 | 17 | 0 | 17 | 2.06 × 10−3 |
GSTM2 | 17 | 0 | 0 | 0 | 17 | 0 | 17 | 0 | 17 | 2.06 × 10−3 |
AHNAK2 | 9 | 3 | 0 | 0 | 9 | 3 | 12 | 0 | 12 | 2.99 × 10−2 |
ID | GENE | EFFECT | p-Value | Beta | CADD |
---|---|---|---|---|---|
13_23808782_T_C | SGCG | Frameshift and missense | 1.10 × 10−5 | 5.21 | 5.754 |
11_133788869_A_G | IGSF9B | Intron | 1.80 × 10−5 | −3.01 | 0.173 |
17_39394962_C_T | KRTAP9-8 | 3_prime_UTR|intron | 2.00 × 10−5 | 2.86 | 3.321 |
2_112939548_T_C | FBLN7 | Intron | 2.10 × 10−5 | 5.07 | 6.004 |
2_112940578_C_T | FBLN7 | Intron | 2.10 × 10−5 | 5.07 | 1.94 |
6_36292007_G_A | BNIP5 | Intron | 2.10 × 10−5 | 4.14 | 0.052 |
16_57068107_C_T | NLRC5 | Frameshift and missense | 2.60 × 10−5 | −4.42 | 1.901 |
16_57071209_T_C | NLRC5 | Intron | 3.40 × 10−5 | −3.92 | 1.492 |
16_57071226_TCC_T | NLRC5 | Intron | 3.40 × 10−5 | −3.92 | 4.507 |
16_57071236_C_T | NLRC5 | Intron | 3.40 × 10−5 | −3.92 | 4.909 |
15_59499179_G_A | LDHAL6B|MYO1E | Frameshift and missense | 3.50 × 10−5 | 2.86 | 8.694 |
15_59500116_T_C | LDHAL6B|MYO1E | frameshift and missense | 3.50 × 10−5 | 2.86 | 23.1 |
16_57075406_T_C | NLRC5 | Frameshift and missense | 3.60 × 10−5 | −4.48 | 8.512 |
16_57076018_G_C | NLRC5 | Intron | 3.60 × 10−5 | −4.48 | 0.213 |
16_57077523_G_A | NLRC5 | Splice region and intron | 3.60 × 10−5 | −4.48 | 2.641 |
16_57077581_C_T | NLRC5 | Intron | 3.60 × 10−5 | −4.48 | 0.278 |
16_57060213_C_T | NLRC5 | Frameshift and missense | 3.60 × 10−5 | −4.48 | 3.843 |
16_57060340_T_C | NLRC5 | Frameshift and missense | 3.60 × 10−5 | −4.48 | 5.063 |
16_57060353_T_C | NLRC5 | Frameshift and missense | 3.60 × 10−5 | −4.48 | 0.581 |
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Shapira, G.; Volkov, H.; Fabian, I.; Mohr, D.W.; Bettinotti, M.; Shomron, N.; Avery, R.K.; Arav-Boger, R. Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients. Viruses 2023, 15, 2227. https://doi.org/10.3390/v15112227
Shapira G, Volkov H, Fabian I, Mohr DW, Bettinotti M, Shomron N, Avery RK, Arav-Boger R. Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients. Viruses. 2023; 15(11):2227. https://doi.org/10.3390/v15112227
Chicago/Turabian StyleShapira, Guy, Hadas Volkov, Itai Fabian, David W. Mohr, Maria Bettinotti, Noam Shomron, Robin K. Avery, and Ravit Arav-Boger. 2023. "Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients" Viruses 15, no. 11: 2227. https://doi.org/10.3390/v15112227
APA StyleShapira, G., Volkov, H., Fabian, I., Mohr, D. W., Bettinotti, M., Shomron, N., Avery, R. K., & Arav-Boger, R. (2023). Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients. Viruses, 15(11), 2227. https://doi.org/10.3390/v15112227