A Genome-Wide Association Study into the Aetiology of Congenital Solitary Functioning Kidney
Abstract
:1. Introduction
2. Patients and Methods
2.1. Patients
2.2. Genotyping
2.3. Quality Control
2.4. Imputation
2.5. Statistical Analyses
3. Results
3.1. Participants
3.2. AGORA Dataset Results
3.3. NBS Dataset Results
3.4. Loci with a Genome-Wide Statistically Significant p-Value
3.5. Other Selected Loci
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Chr | Position | rsID | Discovery Dataset | MAF Patients | MAF Reference | AGORA Dataset | NBS Dataset | n SNVs | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
MAF Controls | OR | p-Value | MAF Controls | OR | p-Value | |||||||
Genome-wide significant SNVs | ||||||||||||
7 | 81228890 | rs140804918 | NBS | 0.048 | 0.031 | 0.029 | 1.91 | 8.4 × 10−3 | 0.020 | 3.10 | 1.4 × 10−8 | 51 |
18 | 73636290 | rs184382636 | NBS | 0.017 | 0.002 | 0.003 | 5.93 | 2.4 × 10−3 | 0.002 | 12.9 | 1.2 × 10−10 | 42 |
SNVs selected based on MAF in discovery and reference populations | ||||||||||||
3 | 189912222 | rs10433490 | NBS | 0.092 | 0.169 | 0.153 | 0.59 | 4.0 × 10−4 | 0.150 | 0.53 | 4.3 × 10−6 | 6 |
6 | 36451716 | rs148413365 | NBS | 0.106 | 0.188 * | 0.156 | 0.94 | 7.0 × 10−1 | 0.166 | 0.51 | 1.9 × 10−6 | 84 |
13 | 38000591 | rs9547854 | NBS | 0.087 | 0.047 | 0.052 | 1.83 | 1.6 × 10−3 | 0.051 | 1.97 | 2.1 × 10−6 | 66 |
14 | 98514525 | rs148251525 | AGORA | 0.127 | 0.048 | 0.075 | 2.08 | 5.2 × 10−6 | 0.106 | 1.22 | 8.2 × 10−2 | 5 |
15 | 89344863 | rs111283115 | AGORA | 0.333 | 0.449 | 0.499 | 0.65 | 7.8 × 10−6 | 0.387 | 0.71 | 3.5 × 10−4 | 24 |
21 | 28122146 | rs2830456 | NBS | 0.281 | 0.370 | 0.410 | 0.64 | 2.5 × 10−5 | 0.350 | 0.63 | 4.5 × 10−6 | 46 |
Other suggestively significant SNVs | ||||||||||||
1 | 79317005 | rs140198115 | NBS | 0.025 | 0.009 | 0.011 | 2.37 | 1.9 × 10−2 | 0.010 | 3.79 | 7.8 × 10−6 | 17 |
1 | 92663276 | rs11406716 | AGORA | 0.319 | 0.283 * | 0.246 | 1.64 | 8.1 × 10−6 | 0.277 | 1.27 | 8.4 × 10−3 | 76 |
3 | 22488640 | rs182382581 | NBS | 0.025 | 0.012 | 0.009 | 4.10 | 1.5 × 10−3 | 0.008 | 5.04 | 8.6 × 10−8 | 7 |
3 | 6328767 | rs7629003 | NBS | 0.009 | 0.003 | 0.003 | 4.68 | 4.9 × 10−2 | 0.002 | 14.48 | 7.6 × 10−6 | 20 |
4 | 106051876 | rs190397903 | NBS | 0.020 | 0.007 | 0.013 | 1.97 | 8.5 × 10−2 | 0.007 | 5.23 | 2.0 × 10−6 | 9 |
4 | 70836149 | rs146356251 | NBS | 0.018 | 0.008 | 0.008 | 2.79 | 2.1 × 10−2 | 0.006 | 4.84 | 7.4 × 10−6 | 7 |
5 | 78674386 | rs138487999 | NBS | 0.034 | 0.019 | 0.016 | 2.33 | 5.5 × 10−3 | 0.014 | 2.84 | 7.4 × 10−6 | 125 |
5 | 139646076 | rs145922969 | NBS | 0.030 | 0.025 | 0.013 | 3.15 | 1.6 × 10−3 | 0.015 | 3.20 | 2.5 × 10−6 | 8 |
5 | 96015902 | rs181945740 | NBS | 0.018 | 0.001 | 0.008 | 4.20 | 7.0 × 10−3 | 0.005 | 5.90 | 1.4 × 10−6 | 7 |
5 | 134199058 | rs73282857 | NBS | 0.019 | 0.006 | 0.005 | 4.68 | 9.4 × 10−3 | 0.006 | 7.00 | 5.6 × 10−8 | 150 |
7 | 10014656 | rs190937828 | NBS | 0.090 | 0.063 | 0.066 | 1.76 | 1.3 × 10−3 | 0.054 | 2.30 | 1.7 × 10−6 | 14 |
8 | 134595232 | rs10112722 | AGORA | 0.437 | 0.366 | 0.347 | 1.55 | 7.5 × 10−6 | 0.370 | 1.34 | 2.3 × 10−4 | 13 |
10 | 44117049 | rs60001082 | NBS | 0.085 | 0.069 * | 0.065 | 1.46 | 4.3 × 10−2 | 0.054 | 2.00 | 7.3 × 10−6 | 17 |
11 | 2275888 | rs1325019515 | AGORA | 0.380 | n/a | 0.305 | 1.61 | 4.9 × 10−6 | 0.312 | 1.40 | 1.1 × 10−4 | 19 |
11 | 58767505 | rs11229723 | NBS | 0.022 | 0.006 | 0.011 | 2.23 | 3.4 × 10−2 | 0.007 | 4.41 | 1.8 × 10−6 | 64 |
11 | 95161244 | rs192152837 | NBS | 0.018 | 0.004 | 0.004 | 10.2 | 2.4 × 10−4 | 0.005 | 6.35 | 3.6 × 10−7 | 8 |
12 | 43256387 | rs181072352 | NBS | 0.012 | 0.005 | 0.008 | 1.44 | 4.8 × 10−1 | 0.002 | 10.40 | 1.2 × 10−6 | 5 |
12 | 385846 | rs554290784 | NBS | 0.015 | 0.005 | 0.004 | 4.23 | 1.1 × 10−2 | 0.003 | 5.59 | 6.8 × 10−6 | 5 |
13 | 75949902 | rs144419778 | AGORA | 0.267 | 0.212 * | 0.19 | 1.71 | 2.7 × 10−6 | 0.205 | 1.47 | 1.9 × 10−5 | 24 |
14 | 60728107 | rs146557102 | NBS | 0.041 | n/a | 0.018 | 2.75 | 4.8 × 10−4 | 0.017 | 2.96 | 5.5 × 10−7 | 8 |
18 | 50196707 | rs77493404 | NBS | 0.022 | 0.009 | 0.014 | 2.25 | 1.2 × 10−2 | 0.008 | 4.23 | 7.5 × 10−6 | 22 |
20 | 44453790 | rs201841698 | NBS | 0.033 | 0.029 | 0.020 | 2.42 | 6.1 × 10−3 | 0.013 | 3.40 | 2.1 × 10−6 | 7 |
20 | 51885312 | rs6126804 | NBS | 0.030 | 0.008 | 0.016 | 2.58 | 7.3 × 10−3 | 0.013 | 3.30 | 6.0 × 10−6 | 8 |
22 | 32945612 | rs73172143 | NBS | 0.095 | 0.078 | 0.068 | 1.47 | 2.7 × 10−2 | 0.059 | 1.88 | 7.0 × 10−6 | 6 |
Chr | rsID | Dataset | Candidate Affected Gene | Distance from SNV to TSS | Regulome Score [36] | Variant Effect Predictor [40] | Gene Function * |
---|---|---|---|---|---|---|---|
Genome-wide significant SNVs | |||||||
7 | rs140804918 | NBS | HGF | 171 kbp | 0.247 | Intergenic | Regulates cell growth, motility and morphogenesis in various cell types and tissues |
18 | rs184382636 | NBS | SMIM21 | 497 kbp | 0.071 | Intergenic | Integral membrane component |
SNVs selected based on MAF in discovery and reference populations | |||||||
3 | rs10433490 | NBS | P3H2 | 72 kbp | 0.154 | Intergenic | Posttranslational modifier of collagen IV |
6 | rs148413365 | NBS | KCTD20 | 41 kbp | 0.163 | Intronic | Member of AKT-mTOR-p70 S6k signalling cascade |
STK38 | 64 kbp | YAP/TAZ inhibitor in hippo pathway | |||||
13 | rs9547854 | NBS | POSTN | 172 kbp | 0.112 | Intergenic | Induces cell attachment and spreading and plays a role in cell adhesion |
14 | rs148251525 | AGORA | BCL11B | 1224 kbp | 0.000 | Intergenic | T cell transcription factor |
15 | rs111283115 | AGORA | ACAN | 1.8 kbp | 0.145 | Upstream gene variant | Major component of extracellular matrix of cartilaginous tissues |
21 | rs2830456 | NBS | ADAMTS1 | 96 kbp | 0.184 | Intergenic | Has antiangiogenic activity, involved in inflammation and cancer cachexia |
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Groen in ’t Woud, S.; Maj, C.; Renkema, K.Y.; Westland, R.; Galesloot, T.; van Rooij, I.A.L.M.; Vermeulen, S.H.; Feitz, W.F.J.; Roeleveld, N.; Schreuder, M.F.; et al. A Genome-Wide Association Study into the Aetiology of Congenital Solitary Functioning Kidney. Biomedicines 2022, 10, 3023. https://doi.org/10.3390/biomedicines10123023
Groen in ’t Woud S, Maj C, Renkema KY, Westland R, Galesloot T, van Rooij IALM, Vermeulen SH, Feitz WFJ, Roeleveld N, Schreuder MF, et al. A Genome-Wide Association Study into the Aetiology of Congenital Solitary Functioning Kidney. Biomedicines. 2022; 10(12):3023. https://doi.org/10.3390/biomedicines10123023
Chicago/Turabian StyleGroen in ’t Woud, Sander, Carlo Maj, Kirsten Y. Renkema, Rik Westland, Tessel Galesloot, Iris A. L. M. van Rooij, Sita H. Vermeulen, Wout F. J. Feitz, Nel Roeleveld, Michiel F. Schreuder, and et al. 2022. "A Genome-Wide Association Study into the Aetiology of Congenital Solitary Functioning Kidney" Biomedicines 10, no. 12: 3023. https://doi.org/10.3390/biomedicines10123023
APA StyleGroen in ’t Woud, S., Maj, C., Renkema, K. Y., Westland, R., Galesloot, T., van Rooij, I. A. L. M., Vermeulen, S. H., Feitz, W. F. J., Roeleveld, N., Schreuder, M. F., & van der Zanden, L. F. M., on behalf of the SOFIA Study Group. (2022). A Genome-Wide Association Study into the Aetiology of Congenital Solitary Functioning Kidney. Biomedicines, 10(12), 3023. https://doi.org/10.3390/biomedicines10123023