Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry
Abstract
:1. Introduction
2. Results
2.1. Participant Characteristics in TWB 2.0 and TWB 1.0
2.2. Glaucoma Risk Loci
2.3. Polygenic Risk Score (PRS) and Glaucoma Risk Prediction
3. Discussion
4. Materials and Methods
4.1. Study Population and Genome-Wide Association Study (GWAS)
4.2. Polygenic Risk Score (PRS) Analyses
4.3. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Discovery TWB2.0 (n = 37,575) | Validation TWB1.0 (n = 7082) | Statistics and p-Values 1,2 | |||||
---|---|---|---|---|---|---|---|
Variables | Case (n = 1013) | Control (n = 36,562) | p-Value 1 | Case (n = 450) | Control (n = 6632) | p-Value 1 | |
Sex | |||||||
Male(%) | 360 (35.54) | 10,889 (29.78) | 9.196 × 10−5 | 225 (50) | 3116 (47) | 0.2335 | <2.2 × 10−16 |
Female(%) | 653 (64.46) | 25,673 (70.22) | 225 (50) | 3516 (53) | |||
Age(years) | 58.18 ± 0.576 | 47.7 ± 0.108 | <2.2 × 10−16 | 58.4 ± 0.4786 | 50.06 ± 0.1332 | <2.2 × 10−16 | <2.2 × 10−16 |
Smoking | Missing: 1 | ||||||
No(%) | 762 (75.22) | 28,062 (76.75) | 0.2713 | 310 (68.89) | 4656 (70.21) | 0.5912 | <2.2 × 10−16 |
Yes(%) | 251 (24.78) | 8499 (23.25) | 140 (31.11) | 1976 (29.79) | |||
Exercise | Missing: 16 | ||||||
No(%) | 480 (47.38) | 22,981 (62.88) | <2.2 × 10−16 | 214 (47.56) | 3750 (56.54) | 0.0002446 | <2.2 × 10−16 |
Yes(%) | 533 (52.62) | 13,565 (37.12) | 236 (52.44) | 2882 (43.46) |
SNP | CHR | Position | Nearest Gene | Minor Allele | MAF (in Cases) | MAF (in Controls) | OR | p-Value (SAIGE) |
---|---|---|---|---|---|---|---|---|
rs2282199 | 9 | 92147093 | LINC00475 | A | 0.3362 | 0.2858 | 1.266 | 6.64 × 10−7 |
rs2282201 | 9 | 92147469 | LINC00475 | A | 0.3362 | 0.2858 | 1.265 | 6.75 × 10−7 |
rs10992252 | 9 | 92150242 | LINC00475 | T | 0.3352 | 0.2856 | 1.261 | 9.78 × 10−7 |
rs57413357 | 9 | 92148753 | LINC00475 | G | 0.335 | 0.2857 | 1.259 | 1.11 × 10−6 |
rs59232045 | 9 | 92140079 | LINC00475 | A | 0.3369 | 0.2875 | 1.259 | 1.39 × 10−6 |
rs4078356 | 6 | 24803089 | RIPOR2 | C | 0.0447 | 0.0264 | 1.727 | 1.82 × 10−6 |
rs10992195 | 9 | 92009252 | LINC00475 | G | 0.3814 | 0.3308 | 1.247 | 1.90 × 10−6 |
rs4757474 | 11 | 16992427 | PLEKHA7 | T | 0.468 | 0.4154 | 1.238 | 2.04 × 10−6 |
rs4757472 | 11 | 16989375 | PLEKHA7 | G | 0.4695 | 0.417 | 1.237 | 2.33 × 10−6 |
rs10832710 | 11 | 16991409 | PLEKHA7 | C | 0.4685 | 0.417 | 1.236 | 2.48 × 10−6 |
chr11:16982833_G_GGA | 11 | 16982833 | PLEKHA7 | G | 0.4863 | 0.4333 | 1.238 | 2.49 × 10−6 |
rs4757475 | 11 | 16994869 | PLEKHA7 | A | 0.4681 | 0.4159 | 1.236 | 2.53 × 10−6 |
rs10832712 | 11 | 16995533 | PLEKHA7 | T | 0.4681 | 0.4159 | 1.236 | 2.53 × 10−6 |
Tuning Parameters 1 | Top N SNPs Included for PRS Calculation | Mean PRS | AUC [95% CI] | |
---|---|---|---|---|
Case | Control | TWB2.0 | ||
p ≤ 10−5 and r2 < 0.2 | 14 | 11.0835 | 9.8500 | 0.6369 [0.6194–0.6543] |
p ≤ 10−5 and r2 < 0.4 | 15 | 12.0615 | 10.7101 | 0.6345 [0.6171–0.6519] |
p ≤ 10−5 and r2 < 0.6 | 18 | 14.8168 | 13.1126 | 0.6105 [0.593–0.6279] |
p ≤ 10−5 and r2 < 0.8 | 18 | 14.8185 | 13.1142 | 0.6104 [0.593–0.6278] |
p ≤ 10−4 and r2 < 0.2 | 134 | 99.3813 | 89.3490 | 0.8387 [0.8269–0.8506] |
p ≤ 10−4 and r2 < 0.4 | 138 | 102.1499 | 91.9352 | 0.8365 [0.8246–0.8484] |
p ≤ 10−4 and r2 < 0.6 | 147 | 109.5890 | 98.3110 | 0.8173 [0.8043–0.8302] |
p ≤ 10−4 and r2 < 0.8 | 162 | 124.4653 | 112.0043 | 0.7984 [0.7847–0.8121] |
Total N = 37,575 | (min, Q1] | (Q1, Q2] | (Q2, Q3] | (Q3, Q4] |
---|---|---|---|---|
Control, N = 36,562 | 9376 | 9326 | 9220 | 8640 |
(n,%) | 25.64% | 25.51% | 25.22% | 23.63% |
Case, N = 1013 | 18 | 68 | 173 | 754 |
(n,%) | 1.78% | 6.71% | 17.08% | 74.43% |
OR [95% C.I] | 1 | 3.80 [2.31, 6.58] | 9.77 [6.19, 16.46] | 45.48 [29.38, 75.39] |
High PRS Group | Reference Group | OR [95% C.I.] |
---|---|---|
Top 25% | Remaining 75% | 9.41 [8.17, 10.87] |
Top 20% | Remaining 80% | 9.72 [8.49, 11.14] |
Top 10% | Remaining 90% | 10.58 [9.31, 12.03] |
Top 5% | Remaining 95% | 13.30 [11.58, 15.26] |
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Hsiao, Y.-J.; Chuang, H.-K.; Chi, S.-C.; Wang, Y.-Y.; Chiang, P.-H.; Teng, P.-C.; Kuang, T.-M.; Yarmishyn, A.A.; Lin, T.-C.; Hwang, D.-K.; et al. Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry. J. Pers. Med. 2021, 11, 1169. https://doi.org/10.3390/jpm11111169
Hsiao Y-J, Chuang H-K, Chi S-C, Wang Y-Y, Chiang P-H, Teng P-C, Kuang T-M, Yarmishyn AA, Lin T-C, Hwang D-K, et al. Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry. Journal of Personalized Medicine. 2021; 11(11):1169. https://doi.org/10.3390/jpm11111169
Chicago/Turabian StyleHsiao, Yu-Jer, Hao-Kai Chuang, Sheng-Chu Chi, Yung-Yu Wang, Pin-Hsuan Chiang, Pai-Chi Teng, Tung-Mei Kuang, Aliaksandr A. Yarmishyn, Tai-Chi Lin, De-Kuang Hwang, and et al. 2021. "Genome-Wide Polygenic Risk Score for Predicting High Risk Glaucoma Individuals of Han Chinese Ancestry" Journal of Personalized Medicine 11, no. 11: 1169. https://doi.org/10.3390/jpm11111169