Exposure Outcome Effect type Point estimate (95%CI) P-value Estimator Heterogeneity P-value Precision No. variants LDL-C CHD (OR) Total 1.50 (1.41; 1.59) < 0.001 IVW < 0.001 1.1×10³ 25 LDL-C CHD (OR) HDL-C independent 1.45 (1.36; 1.56) < 0.001 MR Egger < 0.001 8.1×10² 50 LDL-C CHD (OR) TG independent 1.28 (1.19; 1.37) < 0.001 MR Egger < 0.001 7.4×10² 45 LDL-C CHD (OR) HDL-C & TG independent 1.43 (1.34; 1.52) < 0.001 IVW < 0.001 9.5×10² 57 LDL-C HF (OR) Total 1.00 (0.95; 1.06) 0.926 MR Egger < 0.001 1.2×10³ 111 LDL-C HF (OR) HDL-C independent 1.01 (0.97; 1.05) 0.530 MR Egger < 0.001 2.5×10³ 185 LDL-C HF (OR) TG independent 0.96 (0.92; 1.01) 0.090 MR Egger < 0.001 1.8×10³ 162 LDL-C HF (OR) HDL-C & TG independent 1.00 (0.96; 1.03) 0.848 IVW < 0.001 2.8×10³ 216 LDL-C AF (OR) Total 0.99 (0.96; 1.02) 0.476 IVW 0.080 5.0×10³ 121 LDL-C AF (OR) HDL-C independent 1.00 (0.97; 1.02) 0.875 IVW 0.067 5.5×10³ 202 LDL-C AF (OR) TG independent 0.98 (0.95; 1.01) 0.285 IVW < 0.001 4.2×10³ 181 LDL-C AF (OR) HDL-C & TG independent 0.98 (0.95; 1.01) 0.178 IVW < 0.001 4.0×10³ 238 LDL-C Any stroke (OR) Total 1.04 (0.97; 1.12) 0.261 MR Egger 0.004 7.5×10² 112 LDL-C Any stroke (OR) HDL-C independent 1.03 (0.99; 1.07) 0.106 IVW < 0.001 3.1×10³ 192 LDL-C Any stroke (OR) TG independent 1.01 (0.95; 1.07) 0.722 MR Egger < 0.001 1.2×10³ 167 LDL-C Any stroke (OR) HDL-C & TG independent 1.04 (0.99; 1.09) 0.089 IVW < 0.001 1.9×10³ 228 LDL-C Any ischemic stroke (OR) Total 1.02 (0.94; 1.11) 0.646 MR Egger 0.067 5.3×10² 111 LDL-C Any ischemic stroke (OR) HDL-C independent 1.02 (0.98; 1.06) 0.387 IVW < 0.001 2.5×10³ 189 LDL-C Any ischemic stroke (OR) TG independent 0.99 (0.93; 1.06) 0.843 MR Egger 0.096 8.7×10² 165 LDL-C Any ischemic stroke (OR) HDL-C & TG independent 1.03 (0.98; 1.08) 0.206 IVW 0.010 1.6×10³ 226 LDL-C Large artery stroke (OR) Total 1.12 (1.02; 1.23) 0.018 IVW < 0.001 4.2×10² 113 LDL-C Large artery stroke (OR) HDL-C independent 1.12 (1.02; 1.23) 0.015 IVW < 0.001 4.4×10² 192 LDL-C Large artery stroke (OR) TG independent 1.02 (0.88; 1.19) 0.768 MR Egger < 0.001 1.6×10² 168 LDL-C Large artery stroke (OR) HDL-C & TG independent 1.13 (1.00; 1.27) 0.046 IVW < 0.001 2.7×10² 229 LDL-C Cardioembolic stroke (OR) Total 1.00 (0.93; 1.08) 0.994 IVW 0.026 6.9×10² 114 LDL-C Cardioembolic stroke (OR) HDL-C independent 0.98 (0.91; 1.06) 0.650 IVW 0.039 6.8×10² 191 LDL-C Cardioembolic stroke (OR) TG independent 1.02 (0.89; 1.17) 0.775 MR Egger 0.054 2.2×10² 167 LDL-C Cardioembolic stroke (OR) HDL-C & TG independent 0.99 (0.90; 1.08) 0.769 IVW 0.041 4.4×10² 228 LDL-C Small vessel stroke (OR) Total 0.99 (0.90; 1.08) 0.758 IVW 0.070 4.2×10² 116 LDL-C Small vessel stroke (OR) HDL-C independent 0.95 (0.87; 1.04) 0.254 IVW 0.008 5.1×10² 195 LDL-C Small vessel stroke (OR) TG independent 0.86 (0.75; 0.99) 0.042 MR Egger 0.006 1.9×10² 170 LDL-C Small vessel stroke (OR) HDL-C & TG independent 0.97 (0.87; 1.08) 0.572 IVW 0.007 3.2×10² 232 LDL-C cIMT (mm) Total 0.01 (0.01; 0.02) < 0.001 IVW < 0.001 5.1×10⁵ 116 LDL-C cIMT (mm) HDL-C independent 0.02 (0.01; 0.02) < 0.001 MR Egger < 0.001 2.7×10⁵ 193 LDL-C cIMT (mm) TG independent 0.01 (0.01; 0.02) < 0.001 MR Egger < 0.001 2.0×10⁵ 172 LDL-C cIMT (mm) HDL-C & TG independent 0.02 (0.01; 0.02) < 0.001 MR Egger < 0.001 2.7×10⁵ 234 LDL-C Carotid plaque (OR) Total 1.37 (1.28; 1.46) < 0.001 IVW 0.009 8.7×10² 111 LDL-C Carotid plaque (OR) HDL-C independent 1.27 (1.15; 1.40) < 0.001 MR Egger < 0.001 4.3×10² 187 LDL-C Carotid plaque (OR) TG independent 1.22 (1.09; 1.36) < 0.001 MR Egger 0.013 3.1×10² 162 LDL-C Carotid plaque (OR) HDL-C & TG independent 1.40 (1.29; 1.52) < 0.001 IVW 0.004 5.6×10² 222 LDL-C Glucose (mmol/l) Total 0.02 (-0.00; 0.04) 0.075 MR Egger 0.049 9.2×10³ 115 LDL-C Glucose (mmol/l) HDL-C independent -0.01 (-0.02; 0.00) 0.097 IVW < 0.001 4.1×10⁴ 191 LDL-C Glucose (mmol/l) TG independent 0.01 (-0.01; 0.02) 0.361 MR Egger < 0.001 1.7×10⁴ 172 LDL-C Glucose (mmol/l) HDL-C & TG independent 0.01 (-0.01; 0.02) 0.449 MR Egger < 0.001 2.0×10⁴ 226 LDL-C HbA1c (mmol/mol) Total -0.03 (-0.14; 0.07) 0.520 MR Egger < 0.001 3.4×10² 113 LDL-C HbA1c (mmol/mol) HDL-C independent -0.09 (-0.16; -0.02) 0.013 MR Egger < 0.001 7.7×10² 187 LDL-C HbA1c (mmol/mol) TG independent 0.02 (-0.06; 0.10) 0.587 MR Egger < 0.001 6.2×10² 169 LDL-C HbA1c (mmol/mol) HDL-C & TG independent -0.04 (-0.11; 0.03) 0.248 MR Egger < 0.001 7.8×10² 223 LDL-C T2DM (OR) Total 1.03 (0.98; 1.08) 0.205 MR Egger < 0.001 1.9×10³ 105 LDL-C T2DM (OR) HDL-C independent 0.94 (0.92; 0.96) < 0.001 IVW < 0.001 7.7×10³ 171 LDL-C T2DM (OR) TG independent 0.91 (0.88; 0.94) < 0.001 IVW < 0.001 4.6×10³ 149 LDL-C T2DM (OR) HDL-C & TG independent 0.90 (0.88; 0.93) < 0.001 IVW < 0.001 4.4×10³ 202 LDL-C CRP (mg/L) Total -0.15 (-0.19; -0.11) < 0.001 IVW < 0.001 2.3×10³ 93 LDL-C CRP (mg/L) HDL-C independent -0.21 (-0.26; -0.16) < 0.001 MR Egger < 0.001 1.5×10³ 173 LDL-C CRP (mg/L) TG independent -0.15 (-0.21; -0.10) < 0.001 MR Egger < 0.001 1.2×10³ 155 LDL-C CRP (mg/L) HDL-C & TG independent -0.24 (-0.29; -0.19) < 0.001 IVW < 0.001 1.7×10³ 210 LDL-C SBP (mmHg) Total 0.41 (0.29; 0.54) < 0.001 IVW < 0.001 2.4×10² 90 LDL-C SBP (mmHg) HDL-C independent 0.38 (0.26; 0.50) < 0.001 IVW < 0.001 2.6×10² 156 LDL-C SBP (mmHg) TG independent 0.22 (0.08; 0.37) 0.002 IVW < 0.001 1.9×10² 140 LDL-C SBP (mmHg) HDL-C & TG independent 0.28 (0.13; 0.43) < 0.001 IVW < 0.001 1.8×10² 185 LDL-C DBP (mmHg) Total -0.03 (-0.11; 0.04) 0.356 IVW < 0.001 7.5×10² 91 LDL-C DBP (mmHg) HDL-C independent -0.04 (-0.10; 0.03) 0.306 IVW < 0.001 8.1×10² 156 LDL-C DBP (mmHg) TG independent -0.11 (-0.19; -0.03) 0.007 IVW < 0.001 5.8×10² 139 LDL-C DBP (mmHg) HDL-C & TG independent -0.07 (-0.16; 0.01) 0.080 IVW < 0.001 5.6×10² 187 LDL-C PBL (OR) Total 1.18 (0.96; 1.44) 0.108 IVW 0.084 9.5×10¹ 51 LDL-C PBL (OR) HDL-C independent 1.18 (0.97; 1.43) 0.089 IVW 0.157 1.0×10² 91 LDL-C PBL (OR) TG independent 1.13 (0.81; 1.58) 0.467 MR Egger 0.023 3.4×10¹ 81 LDL-C PBL (OR) HDL-C & TG independent 1.03 (0.78; 1.36) 0.814 MR Egger 0.041 5.0×10¹ 113 LDL-C BUN (mg/dl) Total -0.00 (-0.01; 0.00) 0.481 MR Egger < 0.001 7.7×10⁴ 110 LDL-C BUN (mg/dl) HDL-C independent 0.00 (-0.00; 0.01) 0.130 IVW < 0.001 3.5×10⁵ 181 LDL-C BUN (mg/dl) TG independent 0.00 (-0.00; 0.01) 0.340 MR Egger < 0.001 1.4×10⁵ 165 LDL-C BUN (mg/dl) HDL-C & TG independent 0.00 (-0.00; 0.01) 0.071 IVW < 0.001 2.1×10⁵ 219 LDL-C eGFR (SD of log(eGFR)) Total 0.00 (0.00; 0.01) 0.026 MR Egger < 0.001 5.6×10⁵ 107 LDL-C eGFR (SD of log(eGFR)) HDL-C independent 0.00 (-0.00; 0.00) 0.649 MR Egger < 0.001 1.3×10⁶ 183 LDL-C eGFR (SD of log(eGFR)) TG independent -0.00 (-0.00; 0.00) 0.151 IVW < 0.001 1.6×10⁶ 161 LDL-C eGFR (SD of log(eGFR)) HDL-C & TG independent -0.00 (-0.00; 0.00) 0.239 IVW < 0.001 1.5×10⁶ 214 LDL-C CKD (OR) Total 0.99 (0.95; 1.03) 0.614 IVW 0.058 2.8×10³ 116 LDL-C CKD (OR) HDL-C independent 0.99 (0.95; 1.02) 0.434 IVW 0.027 3.5×10³ 190 LDL-C CKD (OR) TG independent 1.00 (0.94; 1.05) 0.942 MR Egger 0.005 1.3×10³ 171 LDL-C CKD (OR) HDL-C & TG independent 0.99 (0.95; 1.04) 0.720 IVW < 0.001 2.1×10³ 227 LDL-C IBD (OR) Total 1.15 (1.07; 1.22) < 0.001 IVW 0.008 9.4×10² 117 LDL-C IBD (OR) HDL-C independent 1.15 (1.08; 1.22) < 0.001 IVW < 0.001 9.9×10² 196 LDL-C IBD (OR) TG independent 1.16 (1.05; 1.29) 0.003 MR Egger < 0.001 3.7×10² 171 LDL-C IBD (OR) HDL-C & TG independent 1.13 (1.05; 1.23) 0.002 IVW < 0.001 6.1×10² 232 LDL-C UC (OR) Total 1.37 (1.15; 1.63) < 0.001 MR Egger 0.196 1.3×10² 117 LDL-C UC (OR) HDL-C independent 1.24 (1.11; 1.38) < 0.001 MR Egger 0.008 3.3×10² 196 LDL-C UC (OR) TG independent 1.15 (1.04; 1.27) 0.006 IVW 0.002 4.0×10² 176 LDL-C UC (OR) HDL-C & TG independent 1.17 (1.06; 1.30) 0.002 IVW < 0.001 3.8×10² 233 LDL-C CD (OR) Total 1.10 (1.00; 1.20) 0.042 IVW 0.497 5.0×10² 117 LDL-C CD (OR) HDL-C independent 1.09 (1.00; 1.19) 0.054 IVW 0.395 5.2×10² 197 LDL-C CD (OR) TG independent 1.01 (0.87; 1.17) 0.928 MR Egger 0.051 1.8×10² 173 LDL-C CD (OR) HDL-C & TG independent 1.00 (0.89; 1.13) 0.967 IVW 0.056 2.8×10² 233 LDL-C Arthritis (OR) Total 0.93 (0.84; 1.03) 0.158 IVW 0.060 4.0×10² 91 LDL-C Arthritis (OR) HDL-C independent 0.95 (0.87; 1.04) 0.262 IVW 0.212 5.3×10² 157 LDL-C Arthritis (OR) TG independent 1.05 (0.90; 1.23) 0.520 MR Egger 0.181 1.6×10² 141 LDL-C Arthritis (OR) HDL-C & TG independent 0.97 (0.85; 1.11) 0.693 MR Egger 0.186 2.2×10² 185 LDL-C ALS (OR) Total 1.11 (1.04; 1.17) < 0.001 IVW 0.612 1.1×10³ 119 LDL-C ALS (OR) HDL-C independent 1.09 (1.03; 1.15) 0.002 IVW 0.487 1.3×10³ 200 LDL-C ALS (OR) TG independent 1.03 (0.94; 1.13) 0.547 MR Egger 0.292 4.5×10² 175 LDL-C ALS (OR) HDL-C & TG independent 1.05 (0.97; 1.13) 0.196 IVW 0.210 6.8×10² 231 LDL-C MS (OR) Total 1.07 (0.92; 1.24) 0.381 IVW 0.106 1.8×10² 19 LDL-C MS (OR) HDL-C independent 0.86 (0.71; 1.04) 0.119 MR Egger 0.008 1.0×10² 32 LDL-C MS (OR) TG independent 1.11 (0.94; 1.31) 0.209 IVW 0.115 1.5×10² 33 LDL-C MS (OR) HDL-C & TG independent 0.92 (0.77; 1.10) 0.366 MR Egger 0.004 1.2×10² 39 LDL-C Alzheimer (OR) Total 1.01 (0.99; 1.03) 0.484 MR Egger < 0.001 8.6×10³ 82 LDL-C Alzheimer (OR) HDL-C independent 1.05 (1.04; 1.07) < 0.001 MR Egger < 0.001 1.8×10⁴ 156 LDL-C Alzheimer (OR) TG independent 1.05 (1.03; 1.06) < 0.001 IVW < 0.001 2.2×10⁴ 135 LDL-C Alzheimer (OR) HDL-C & TG independent 1.05 (1.04; 1.07) < 0.001 MR Egger < 0.001 1.9×10⁴ 198 LDL-C Parkinson (OR) Total 0.93 (0.81; 1.07) 0.315 MR Egger 0.216 1.9×10² 117 LDL-C Parkinson (OR) HDL-C independent 0.93 (0.87; 1.00) 0.050 IVW 0.082 7.9×10² 189 LDL-C Parkinson (OR) TG independent 0.94 (0.86; 1.02) 0.133 IVW 0.002 5.6×10² 174 LDL-C Parkinson (OR) HDL-C & TG independent 0.93 (0.85; 1.01) 0.096 IVW < 0.001 5.3×10² 230 LDL-C Pancreatic cancer (OR) Total 1.20 (0.99; 1.46) 0.066 IVW 0.002 1.0×10² 117 LDL-C Pancreatic cancer (OR) HDL-C independent 1.11 (0.91; 1.34) 0.305 IVW 0.003 1.0×10² 192 LDL-C Pancreatic cancer (OR) TG independent 1.34 (1.06; 1.69) 0.014 IVW 0.021 7.1×10¹ 177 LDL-C Pancreatic cancer (OR) HDL-C & TG independent 1.14 (0.90; 1.45) 0.269 IVW < 0.001 6.8×10¹ 233 LDL-C Colon cancer (OR) Total 0.95 (0.79; 1.13) 0.548 MR Egger 0.087 1.2×10² 118 LDL-C Colon cancer (OR) HDL-C independent 0.99 (0.89; 1.11) 0.890 MR Egger < 0.001 3.2×10² 198 LDL-C Colon cancer (OR) TG independent 1.03 (0.93; 1.14) 0.580 IVW < 0.001 3.9×10² 177 LDL-C Colon cancer (OR) HDL-C & TG independent 1.02 (0.92; 1.12) 0.754 IVW < 0.001 3.9×10² 236 LDL-C Rectal cancer (OR) Total 1.21 (1.08; 1.35) < 0.001 IVW 0.833 3.1×10² 116 LDL-C Rectal cancer (OR) HDL-C independent 1.17 (1.05; 1.30) 0.005 IVW 0.500 3.3×10² 193 LDL-C Rectal cancer (OR) TG independent 1.20 (1.05; 1.37) 0.009 IVW 0.840 2.1×10² 176 LDL-C Rectal cancer (OR) HDL-C & TG independent 1.28 (1.12; 1.47) < 0.001 IVW 0.586 2.1×10² 231 LDL-C Melanoma (OR) Total 0.92 (0.86; 0.99) 0.018 IVW 0.171 8.6×10² 117 LDL-C Melanoma (OR) HDL-C independent 0.93 (0.87; 0.99) 0.024 IVW 0.014 9.9×10² 191 LDL-C Melanoma (OR) TG independent 0.90 (0.84; 0.97) 0.008 IVW 0.024 6.6×10² 176 LDL-C Melanoma (OR) HDL-C & TG independent 0.90 (0.83; 0.97) 0.008 IVW < 0.001 6.5×10² 231 LDL-C Lung cancer (OR) Total 0.76 (0.69; 0.84) < 0.001 IVW 0.045 3.6×10² 116 LDL-C Lung cancer (OR) HDL-C independent 0.78 (0.70; 0.86) < 0.001 IVW 0.017 3.8×10² 194 LDL-C Lung cancer (OR) TG independent 0.77 (0.68; 0.88) < 0.001 IVW 0.061 2.2×10² 177 LDL-C Lung cancer (OR) HDL-C & TG independent 0.77 (0.68; 0.87) < 0.001 IVW 0.022 2.5×10² 235