Table 3.
Observational and MR analyses of all‐cause and cause‐specific mortality by BMI in male UK Biobank participants of White British ancestry
| Cause of death | n a | Observational | MR analyses | DWHc | ||||
|---|---|---|---|---|---|---|---|---|
| Unadjusted | Adjusted | |||||||
| HR (95% CI)b | P | HR (95% CI)a | P | HR (95% CI)b | P | |||
| All‐cause d | 5,882 | 1.03 (1.02‐1.03) | 4.00 × 10‐18 | 1.02 (1.01‐1.03) | 1.59 × 10‐07 | 1.03 (0.98‐1.08) | 0.26 | 0.93 |
| Cardiovascular disease d | 1,467 | 1.08 (1.07‐1.09) | 1.23 × 10‐48 | 1.08 (1.06‐1.09) | 7.39 × 10‐28 | 1.09 (0.98‐1.20) | 0.10 | 0.88 |
| Coronary heart disease | 906 | 1.08 (1.07‐1.09) | 8.84 × 10‐32 | 1.08 (1.06‐1.10) | 4.80 × 10‐18 | 1.12 (0.98‐1.27) | 0.09 | 0.62 |
| Stroke | 194 | 1.03 (0.99‐1.06) | 0.10 | 1.02 (0.98‐1.07) | 0.29 | 1.01 (0.76‐1.33) | 0.96 | 0.88 |
| Aortic aneurysm | 83 | 1.04 (0.99‐1.09) | 0.14 | 1.03 (0.97‐1.09) | 0.40 | 0.80 (0.52‐1.21) | 0.29 | 0.22 |
| Other cardiovascular diseases | 284 | 1.11 (1.09‐1.14) | 9.96 × 10‐25 | 1.11 (1.08‐1.14) | 9.99 × 10‐15 | 1.16 (0.92‐1.45) | 0.21 | 0.75 |
| Respiratory diseases | 361 | 0.94 (0.91‐0.97) | 1.08 × 10‐05 | 0.91 (0.88‐0.95) | 2.22 × 10‐06 | 1.04 (0.85‐1.27) | 0.71 | 0.32 |
| Cancer d | 3,113 | 1.01 (1.00‐1.02) | 0.002 | 1.01 (1.00‐1.02) | 0.06 | 1.00 (0.93‐1.07) | 0.98 | 0.72 |
| Lung cancer | 571 | 0.96 (0.94‐0.98) | 0.0002 | 0.94 (0.91‐0.97) | 4.27 × 10‐05 | 0.92 (0.78‐1.08) | 0.29 | 0.57 |
| Prostate cancer | 308 | 1.03 (1.01‐1.06) | 0.01 | 1.05 (1.02‐1.08) | 0.004 | 0.87 (0.70‐1.08) | 0.21 | 0.12 |
| Colorectal cancer | 329 | 1.03 (1.00‐1.05) | 0.04 | 1.02 (0.99‐1.05) | 0.23 | 1.09 (0.88‐1.34) | 0.43 | 0.59 |
| Pancreatic cancer | 201 | 1.01 (0.97‐1.04) | 0.76 | 1.00 (0.96‐1.04) | 0.97 | 1.18 (0.90‐1.54) | 0.24 | 0.25 |
| Stomach cancer | 105 | 1.07 (1.03‐1.11) | 0.001 | 1.06 (1.01‐1.12) | 0.02 | 1.15 (0.79‐1.68) | 0.45 | 0.70 |
| Esophageal cancer | 226 | 1.06 (1.03‐1.09) | 1.06 × 10‐04 | 1.07 (1.03‐1.11) | 1.17 × 10‐04 | 1.28 (0.99‐1.65) | 0.06 | 0.14 |
| Malignant melanoma | 78 | 0.99 (0.94‐1.05) | 0.85 | 0.97 (0.91‐1.04) | 0.42 | 0.99 (0.64‐1.53) | 0.96 | 0.98 |
| Kidney cancer | 137 | 1.09 (1.05‐1.12) | 8.27 × 10‐07 | 1.08 (1.03‐1.13) | 5.72 × 10‐04 | 1.04 (0.75‐1.44) | 0.82 | 0.79 |
| Bladder cancer | 78 | 0.98 (0.93 ‐1.04) | 0.58 | 0.93 (0.86 ‐1.00) | 0.05 | 0.73 (0.47 ‐1.13) | 0.16 | 0.18 |
| Brain cancer | 169 | 1.01 (0.97‐1.05) | 0.59 | 0.98 (0.94‐1.03) | 0.47 | 1.15 (0.85‐1.54) | 0.36 | 0.39 |
| Liver cancer | 100 | 1.11 (1.07‐1.15) | 3.18 × 10‐08 | 1.08 (1.03‐1.13) | 0.003 | 1.03 (0.70‐1.52) | 0.86 | 0.73 |
| Lymphatic cancer | 329 | 1.00 (0.97‐1.03) | 0.91 | 1.01 (0.98‐1.04) | 0.58 | 1.03 (0.83‐1.27) | 0.81 | 0.79 |
| Other cancers | 460 | 0.99 (0.96‐1.01) | 0.22 | 1.00 (0.98‐1.03) | 0.88 | 0.89 (0.74‐1.06) | 0.20 | 0.26 |
| External causes | 206 | 0.97 (0.94‐1.01) | 0.12 | 0.97 (0.93‐1.01) | 0.11 | 1.11 (0.85‐1.45) | 0.44 | 0.32 |
Number of deaths from all causes or cause‐specific mortality.
Adjusted for secular trends (date of birth); estimates represent HR with each unit increase in BMI (kg/m2).
Adjusted for secular trends (date of birth), highest household occupation, education, smoking status, alcohol intake, and physical activity.
Adjusted for secular trends (date of birth) and first 10 genetic principal components.
P value for comparing estimates derived from observational and MR analyses using simplification of matrix method for DWH test statistic (see Supporting Information Methods).
Total number of male UK Biobank participants who had died by February 16, 2016, from any cause (or those specifically defined as cardiovascular disease or cancer), which was stratified further into primary diseases of focus (excluding mortality causes with fewer than 40 deaths and all other causes; see Supporting Information Table S1b).
DWH, Durbin‐Wu‐Hausman; MR, Mendelian randomization.