Background
Methods
Study sample
Genotyping of UGT1A1*28 locus
Analytic approach
Mendelian randomization
Causal assumptions
Statistical methods
Traditional Approach | Mendelian Randomization Approach | ||||||
---|---|---|---|---|---|---|---|
Trait | Estimate (95% CI) |
p
| 6/6 mean (SD) | 6/7 mean (SD) | 7/7 mean (SD) | 7/7 vs 6 carriers p
| Estimate (95% CI) |
Body Mass Index (kg/m2) | -1.5 (-2.4, -0.5) | 0.003 | 26.6 (4.7) | 26.5 (4.3) | 27.0 (4.6) | 0.43 | 0.6 (-0.5, 1.6) |
Waist Circumference (cm) | -1.9 (-4.2, 0.4) | 0.11 | 87.5 (11.2) | 86.9 (10.8) | 88.0 (11.1) | 0.16 | 2.4 (0.0, 5.2) |
SBP (mmHg) | -2.8 (-5.9, 0.3) | 0.08 | 122.4 (14.3) | 120.9 (15.4) | 120.6 (13.5) | 0.50 | -1.9 (-4.8, 1.9) |
DBP (mmHg) | -1.7 (-3.5, 0.1) | 0.07 | 77.7 (8.5) | 76.2 (8.6) | 76.4 (8.9) | 0.74 | 0.7 (-2.6, 1.8) |
Heart Rate (/s) | -0.9 (-3.0, 1.3) | 0.43 | 79.0 (8.5) | 78.0 (7.8) | 78.4 (8.9) | 0.77 | -0.5 (-3.1, 2.3) |
Triglycerides (mg/dl) | -7.4 (-16.2, 1.4) | 0.10 | 68.4 (42.7) | 67.0 (40.5) | 71.9 (41.6) | 0.39 | 5.7 (-4.1, 15.8) |
Fasting HDL Cholesterol (mg/dl) | -1.4 (-4.4, 1.7) | 0.38 | 56.4 (14.3) | 55.6 (14.5) | 55.2 (14.9) | 0.28 | -2.5 (-5.7, 0.7) |
Fasting LDL Cholesterol (mg/dl) | -15.9 (-24.8, -7.0) | 0.0005 | 141.0 (44.5) | 137.5 (41.7) | 139.4 (44.6) | 0.62 | -3.4 (-13.9, 8.6) |
Fasting Total Cholesterol (mg/dl) | -18.6 (-28.3, -8.9) | 0.0002 | 211.1 (48.5) | 206.5 (45.9) | 209.0 (46.8) | 0.54 | -4.6 (-15.4, 7.5) |
Common Carotid IMT (mm) | -0.03 (-0.06, 0.01) | 0.12 | 0.6 (0.2) | 0.6 (0.2) | 0.6 (0.2) | 0.65 | 0.0 (-0.03, 0.05) |
C Reactive Protein (mg/l) | -0.9 (-1.9, 0.1) | 0.07 | 1.9 (3.8) | 2.3 (6.2) | 1.7 (2.1) | 0.31 | -0.8 (-1.4, 0.1) |
Pulse Wave Velocity (m/s) | -0.08 (-0.4, 0.2) | 0.57 | 5.3 (1.3) | 5.2 (1.1) | 5.4 (1.3) | 0.17 | 0.3 (0.0, 0.6) |
CPT SBP (mmHg*min) | 1.4 (-2.2, 4.9) | 0.45 | 28.8 (17.0) | 27.2 (15.6) | 31.6 (16.3) | 0.02 | 6.1 (2.1, 10.4) |
CPT DBP (mmHg*min) | 1.7 (-0.7, 4.2) | 0.17 | 16.5 (11.8) | 15.8 (10.5) | 18.7 (11.6) | 0.01 | 5.0 (2.4, 8.1) |
Flow Mediated Dilation (%) | 0.7 (-0.8, 2.1) | 0.37 | 9.7 (5.7) | 10.5 (5.8) | 11.3 (6.4) | 0.12 | 1.6 (-0.2, 3.2) |
Brachial Artery Diameter (mm) | -0.5 (-1.8, 0.7) | 0.40 | 28.2 (5.0) | 27.7 (5.4) | 26.2 (4.6) | 0.003 | -1.9 (-2.7, -1.0) |
Results
Sample characteristics
Characteristic | Men (n = 460) | Women (n = 408) |
---|---|---|
Age (yrs) | 42.2 (13.6) | 45.4 (14.2) |
BMI (kg/m2) | 25.6 (3.2) | 27.8 (5.5) |
Total Cholesterol (mg/dl) | 202.5 (44.3) | 215.7 (49.0) |
Triglycerides (mg/dl) | 63.9 (1.7) | 73.8 (45.4) |
SBP (mmHg) | 121.5 (12.6) | 121.4 (16.9) |
DBP (mmHg) | 77.6 (8.8) | 75.8 (8.4) |
Diabetes (%) | 0.9 | 1.0 |
Current Smokers (%)* | 20.0 | 0.0 |
Lipid Lowering Meds (%)** | 1.0 | 1.0 |
Antihypertensive Meds (%)** | 0.2 | 0.3 |
Trait | 6/6 (n = 296) | 6/7 (n = 392) | 7/7 (n = 173) | 7/7 vs. 6/6-6/7 |
---|---|---|---|---|
Gender,% male | 58.1% | 53.1% | 46.2% | 0.03 |
Age, yrs (SD) | 44.0 (13.6) | 43.0 (14.3) | 44.6 (13.7) | 0.49 |
Bilirubin, mg/dL (SD) | 0.42 (0.14) | 0.49 (0.18) | 0.99 (0.42) | < 0.0001 |