Polycystic Ovary Syndrome and Risk of Type 2 Diabetes, Coronary Heart Disease, and Stroke
Article Figures & Tables
Figures
- Figure 1
Relationships among risk factors, PCOS, and cardiometabolic events suggested by MR. Each solid arrow represents a positive genetic correlation documented by MR, indicating possible causal relationships. The relationship between increased testosterone and PCOS applies only to women. These relationships may explain the epidemiologic associations among PCOS and CHD and diabetes. The dotted arrows represent the negative MR results of the current study. T, testosterone.
Tables
- Table 1
PCOS SNPs used to construct the main instrument variable in Europeans
Chr:position SNP Effect allele Other allele EAF β SE Nearest gene P F statistic 2:43561780 rs7563201 A G 0.451 −0.108 0.017 THADA 3.68E−10 39.50 2:213391766 rs2178575 A G 0.151 0.166 0.022 ERBB4 3.34E−14 57.66 5:131813204 rs13164856 T C 0.729 0.124 0.019 IRF1/RAD50 1.45E−10 40.95 8:11623889 rs804279 A T 0.262 0.128 0.018 GATA4/NEIL2 3.76E−12 48.09 9:5440589 rs10739076 A C 0.308 0.110 0.020 PLGRKT 2.51E−08 31.01 9:97723266 rs7864171 A G 0.428 −0.093 0.017 C9orf3 2.95E−08 30.84 9:126619233 rs9696009 A G 0.068 0.202 0.031 DENND1A 7.96E−11 42.19 11:30226356 rs11031005 T C 0.854 −0.159 0.022 ARL14EP/FSHB 8.66E−13 51.03 11:102043240 rs11225154 A G 0.094 0.179 0.027 YAP1 5.44E−11 43.16 11:113949232 rs1784692 T C 0.824 0.144 0.023 ZBTB16 1.88E−10 40.49 12:56477694 rs2271194 A T 0.416 0.097 0.017 ERBB3/RAB5B 4.57E−09 34.22 12:75941042 rs1795379 T C 0.240 −0.117 0.020 KRR1 1.81E−09 36.25 16:52375777 rs8043701 A T 0.815 −0.127 0.021 TOX3 9.61E−10 37.46 2:49247832 rs2349415 T C 0.343 0.076 0.017 FSHR 9.59E−06 19.65 Chr, chromosome; EAF, effect allele frequency.
- Table 2
PCOS SNPs used to construct the main instrument variable in East Asians
Chr:position SNP Effect allele Other allele EAF β SE Nearest gene P F statistic 2:43638838 rs13429458 A C 0.81 0.401 0.040 THADA 1.73E−23 99.75 2:48978159 rs13405728 A G 0.754 0.343 0.037 LHCGR 7.55E−21 87.72 2:49201612 rs2268361 C T 0.504 0.139 0.020 FSHR 9.89E−13 50.87 2:49247832 rs2349415 T C 0.181 0.174 0.025 FSHR 2.35E−12 49.17 9:97648587 rs4385527 G A 0.781 0.174 0.030 C9orf3 5.87E−09 33.88 9:97741336 rs3802457 G A 0.904 0.261 0.035 C9orf3 5.28E−14 56.62 9:126525212 rs2479106 G A 0.222 0.293 0.033 DENND1A 8.12E−19 78.47 11:102070639 rs1894116 G A 0.194 0.239 0.024 YAP1 1.08E−22 96.12 12:56390636 rs705702 G A 0.245 0.239 0.023 RAB5B/SUOX 8.64E−26 110.25 12:66224461 rs2272046 A C 0.907 0.357 0.038 HMGA2 1.95E−21 90.4 16:52347819 rs4784165 G T 0.325 0.140 0.021 TOX3 3.64E−11 43.8 19:7166109 rs2059807 G A 0.301 0.131 0.023 INSR 1.09E−08 32.67 20:52447303 rs6022786 A G 0.339 0.122 0.020 SUMO1P1 1.83E−09 36.15 Chr, chromosome; EAF, effect allele frequency.
- Table 3
Characteristics of the outcome data sources used for MR analyses
Trait No. of case subjects No. of control subjects Consortium Population Year Diabetes in Asian (all subjects) 77,418 356,122 AGEN Asian 2020 Female 27,370 135,055 AGEN Asian 2020 Male 28,027 89,312 AGEN Asian 2020 Diabetes in European (all subjects) 74,124 824,006 DIAMANTE European 2018 Female 30,053 434,336 DIAMANTE European 2018 Male 41,846 383,767 DIAMANTE European 2018 CHD 122,733 424,528 UKBB plus CARDIoGRAMplusC4D Majority European 2018 Any stroke 40,585 406,111 MEGASTROKE European 2018 Any ischemic stroke 34,217 406,111 MEGASTROKE European 2018 Large artery stroke 4,373 406,111 MEGASTROKE European 2018 Cardioembolic stroke 7,193 406,111 MEGASTROKE European 2018 Small vessel stroke 5,386 406,111 MEGASTROKE European 2018 - Table 4
Associations between genetically predicted PCOS and risk of type 2 diabetes, CHD, and stroke with use of the IVW method
Trait IVW Cochran Q statistic OR (95% CI) P Test statistic P Diabetes in Asian (all) 0.98 (0.96–1.01) 0.13 23.48 0.02 Female 0.98 (0.95–1.02) 0.33 11.40 0.50 Male 0.99 (0.95–1.02) 0.45 14.45 0.27 Diabetes in European (all) 0.97 (0.92–1.01) 0.16 29.79 0.005 Female 0.95 (0.88–1.02) 0.16 29.38 0.006 Male 0.98 (0.93–1.03) 0.42 15.66 0.27 CHD 1.00 (0.96–1.04) 0.88 24.42 0.03 Any stroke 0.98 (0.93–1.02) 0.33 10.21 0.68 Any ischemic stroke 0.98 (0.93–1.03) 0.40 8.26 0.83 Large artery stroke 0.88 (0.78–1.00) 0.06 12.16 0.51 Cardioembolic stroke 0.92 (0.83–1.02) 0.10 13.88 0.38 Small vessel stroke 1.10 (0.95–1.27) 0.21 18.59 0.14 - Table 5
Associations between genetically predicted PCOS and risk of type 2 diabetes, CHD, and stroke with use of MR-Egger and weighted median methods
Trait MR-Egger Weighted median OR (95% CI) P Intercept PInter OR (95% CI) P Diabetes in Asian (all) 0.96 (0.90–1.03) 0.29 0.005 0.58 0.99 (0.96–1.02) 0.42 Female 0.96 (0.88–1.04) 0.29 0.01 0.44 0.99 (0.94–1.03) 0.53 Male 0.99 (0.90–1.09) 0.83 −0.001 0.94 0.98 (0.93–1.02) 0.34 Diabetes in European (all) 1.00 (0.81–1.24) 1.00 −0.004 0.75 0.95 (0.91–1.01) 0.08 Female 0.97 (0.70–1.35) 0.87 −0.003 0.88 0.88 (0.82–0.96) 0.003 Male 1.02 (0.82–1.25) 0.88 −0.005 0.73 0.97 (0.91–1.04) 0.40 CHD 0.91 (0.77–1.06) 0.24 0.01 0.24 0.99 (0.95–1.04) 0.76 Any stroke 1.06 (0.87–1.29) 0.58 −0.01 0.43 1.00 (0.94–1.07) 0.90 Any ischemic stroke 1.04 (0.83–1.30) 0.73 −0.01 0.59 0.99 (0.92–1.06) 0.72 Large artery stroke 1.02 (0.60–1.74) 0.95 −0.02 0.60 0.91 (0.77–1.08) 0.29 Cardioembolic stroke 1.07 (0.69–1.66) 0.77 −0.02 0.50 0.94 (0.82–1.08) 0.38 Small vessel stroke 0.88 (0.48–1.62) 0.69 0.03 0.48 1.09 (0.92–1.29) 0.33 PInter, intercept P value.
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