Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke
Abstract
:1. Introduction
2. Methods
2.1. Study Population and Outcome Assessments
2.2. DNA Extraction and Genome-Wide Detection of CNV
2.3. Pathway Analysis
2.4. Statistical Analysis
3. Results
3.1. General CNV Pattern and Association with the Risk of Thromboembolic Stroke Induced by AF
3.2. Functional Integration of Identified CNVs and Genes by Pathway Analysis
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variables | AF with Stroke (n = 109) | Controls (n = 14,666) |
---|---|---|
Age (yr) * | 71 ± 12 | 48 ± 11 |
Male (%) | 53 (48.6) | 7246 (49.4) |
DM (%) | 9 (8.3) | 656 (4.4) |
HTN (%) | 18 (16.5) | 1589 (10.8) |
HPL (%) | 11 (10.1) | 848 (5.7) |
CNV Region | Cytoband | Start Position | Type | Allele Frequency | Avg CN | Length (bps) | Nearest Feature | p | ln(OR) (95% CI) |
---|---|---|---|---|---|---|---|---|---|
Region 1 | 1p36.33 | 565433 | Del | 0.30 | 1.45 | 1,614,263 | GNB1, PRKCZ | 1.69 × 10−10 | 15.3 (12.9–17.7) |
1p36.33-1p36.32 | 2179695 | Del | 0.30 | 1.45 | 298,359 | RP3-395M20.12 | 2.14 × 10−11 | 17.5 (14.9–20.1) | |
1p36.32 | 2478053 | Del | 0.28 | 1.44 | 391,244 | RP11-740P5.3 | 2.95 × 10−9 | 15.8 (13.1–18.4) | |
1p36.32 | 2869296 | Del | 0.27 | 1.43 | 293,652 | PRDM16 | 6.24 × 10−9- | 13.8 (11.5–16.2) | |
1p36.32 | 3162947 | Del | 0.26 | 1.42 | 10,249 | PRDM16 | 8.58 × 10−9 | 13.8 (11.4–16.2) | |
1p36.32 | 3173195 | Del | 0.24 | 1.41 | 184,908 | PRDM16 | 1.44 × 10−8 | 13.8 (11.3–16.2) | |
1p36.32 | 3358102 | Del | 0.24 | 1.41 | 297,333 | TP73-AS1 | 5.09 × 10−9 | 15.8 (13.1–18.5) | |
1p36.32 | 3655434 | Del | 0.23 | 1.41 | 7371 | TP73-AS1 | 5.53 × 10−9 | 15.8 (13.1–18.5) | |
1p36.32 | 3662804 | Del | 0.22 | 1.41 | 18,596 | CCDC27 | 3.44 × 10−7 | 14.4 (11.6–17.2) | |
1p36.32 | 3681399 | Del | 0.21 | 1.40 | 11,306 | SMIM1 | 3.86 × 10−7 | 14.4 (11.6–17.3) | |
1p36.32 | 3692704 | Del | 0.20 | 1.39 | 3565 | SMIM1 | 5.03 × 10−7 | 14.4 (11.5–17.2) | |
1p36.32 | 3696268 | Del | 0.19 | 1.38 | 45,605 | CEP104 | 5.74 × 10−7 | 14.4 (11.5–17.3) | |
1p36.32 | 3741872 | Del | 0.17 | 1.36 | 58,040 | DFFB | 1.2 × 10−5 | 11.9 (9.2–14.7) | |
1p36.32 | 3799911 | Del | 0.17 | 1.36 | 205,245 | RP13-614K11.1 | 1.53 × 10−5 | 11.9 (9.2–14.7) | |
Region 2 | 5p15.33 | 1313855 | Del | 0.16 | 1.39 | 158,260 | LPCAT1 | 1.9 × 10−5 | 10.0 (7.7–12.4) |
5p15.33 | 1472114 | Del | 0.16 | 1.39 | 193,377 | RP11-43F13.1 | 5.24 × 10−5 | 13.3 (10.0–16.6) | |
Region 3 | 8q24.3 | 144283121 | Del | 0.16 | 1.43 | 357,744 | GSDMD | 5.56 × 10−6 | 8.5 (6.6–10.4) |
Region 4 | 14q11.2 | 22754700 | Amp | 0.15 | 2.45 | 1721 | TRAV38-2DV8 | 8.23 × 10−7 | 12.6 (10.0–15.1) |
14q11.2 | 22756420 | Amp | 0.16 | 2.46 | 178,718 | TRDC | 1.79 × 10−9 | 14.6 (12.1–17.0) | |
14q11.2 | 22935137 | Amp | 0.15 | 2.46 | 7248 | TRDV3 | 1.68 × 10−8 | 14.2 (11.7–16.7) | |
Region 5 | 19p13.3 | 2089647 | Del | 0.20 | 1.30 | 38,105 | AP3D1 | 1.64 × 10−6 | 6.9 (5.5–8.3) |
19p13.3 | 2127751 | Del | 0.20 | 1.34 | 23,119 | AP3D1 | 6.25 × 10−7 | 8.2 (6.5–9.8) | |
19p13.3 | 2150869 | Del | 0.19 | 1.35 | 19,047 | DOT1L | 3.97 × 10−8 | 11 (9.0–13.0) | |
19p13.3 | 2169915 | Del | 0.19 | 1.35 | 945 | DOT1L | 3.33 × 10−7 | 7.4 (6.0–8.9) | |
19p13.3 | 2170859 | Del | 0.19 | 1.35 | 139,329 | LINGO3 | 2.2 × 10−7 | 8.4 (6.8–10.5) | |
19p13.3 | 2310187 | Del | 0.19 | 1.36 | 4407 | LSM7 | 3.57 × 10−8 | 11.0 (9.0–13.0) | |
19p13.3 | 2314593 | Del | 0.17 | 1.35 | 86,339 | TMPRSS9 | 1.44 × 10−6 | 9.9 (7.8–11.9) | |
19p13.3 | 2400931 | Del | 0.17 | 1.33 | 3631 | TMPRSS9 | 2.7 × 10−6 | 9.7 (7.7–11.8) | |
19p13.3 | 2404561 | Del | 0.16 | 1.32 | 73,270 | GADD45B | 6.5 × 10−6 | 9.5 (7.4–11.7) | |
19p13.3 | 2477830 | Del | 0.15 | 1.32 | 30,337 | RNU6-993P | 8.82 × 10−6 | 9.5 (7.4–11.7) | |
19p13.3 | 2508166 | Del | 0.15 | 1.34 | 21,100 | GNG7 | 3.21 × 10−6 | 10 (7.8–12.1) |
Gene Symbol | Cytoband | Entrez Gene Name | Location | Type(s) |
---|---|---|---|---|
GNB1 | 1p36.32 | G protein subunit beta 1 | Plasma Membrane | enzyme |
GNG7 | 19p13.3 | G protein subunit gamma 7 | Plasma Membrane | enzyme |
PRKCZ | 1p36.32 | protein kinase C zeta | Cytoplasm | kinase |
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Hsieh, C.-S.; Huang, P.-S.; Chang, S.-N.; Wu, C.-K.; Hwang, J.-J.; Chuang, E.Y.; Tsai, C.-T. Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke. J. Clin. Med. 2019, 8, 332. https://doi.org/10.3390/jcm8030332
Hsieh C-S, Huang P-S, Chang S-N, Wu C-K, Hwang J-J, Chuang EY, Tsai C-T. Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke. Journal of Clinical Medicine. 2019; 8(3):332. https://doi.org/10.3390/jcm8030332
Chicago/Turabian StyleHsieh, Chia-Shan, Pang-Shuo Huang, Sheng-Nan Chang, Cho-Kai Wu, Juey-Jen Hwang, Eric Y. Chuang, and Chia-Ti Tsai. 2019. "Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke" Journal of Clinical Medicine 8, no. 3: 332. https://doi.org/10.3390/jcm8030332