Table 3.
Age-stratified observational and IV analysis based on a genetic score of the association of adiposity with cardiovascular risk factors
| <55 years |
≥55 years | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| n | β (95% CI) | P* | PIV-obs* | n | β (95% CI) | P* | PIV-obs* | Pdiff* | |
| Observational analyses | |||||||||
| Diastolic blood pressure | 71,588 | 0.29 (0.26–0.32) | 2.7 × 10−98 | 48,210 | 0.23 (0.19–0.27) | 4.4 × 10−35 | 0.01 | ||
| Systolic blood pressure | 71,753 | 0.25 (0.22–0.27) | 2.3 × 10−85 | 48,596 | 0.22 (0.18–0.26) | 2.0 × 10−26 | 0.19 | ||
| Fasting glucose | 45,047 | 0.16 (0.13–0.20) | 7.3 × 10−21 | 25,089 | 0.24 (0.20–0.27) | 4.7 × 10−37 | 0.005 | ||
| 2-h post-OGTT glucose | 13,778 | 0.18 (0.10–0.25) | 3.1 × 10−6 | 8,426 | 0.21 (0.09–0.32) | 4.6 × 10−4 | 0.66 | ||
| HbA1c | 14,824 | 0.13 (0.07–0.20) | 1.1 × 10−4 | 14,397 | 0.18 (0.12–0.24) | 8.8 × 10−9 | 0.35 | ||
| ln fasting insulin | 26,322 | 0.48 (0.44–0.52) | 1.8 × 10−118 | 14,815 | 0.50 (0.45–0.54) | 1.6 × 10−97 | 0.57 | ||
| ln CRP | 41,854 | 0.40 (0.37–0.43) | 2.5 × 10−175 | 30,090 | 0.30 (0.26–0.33) | 2.4 × 10−68 | 2.51 × 10−6 | ||
| ln IL-6 | 6,719 | 0.16 (0.06–0.26) | 0.001 | 5,159 | 0.14 (0.08–0.21) | 1.9 × 10−5 | 0.73 | ||
| HDL-C | 57,672 | −0.28 (−0.30 to −0.27) | 1.1 × 10−304 | 36,171 | −0.28 (−0.31 to −0.25) | 9.1 × 10−99 | 0.83 | ||
| LDL-C | 56,392 | 0.16 (0.13–0.18) | 4.4 × 10−33 | 31,499 | 0.02 (0.00–0.04) | 0.08 | 9.73 × 10−16 | ||
| Total cholesterol | 69,736 | 0.12 (0.10–0.15) | 9.8 × 10−23 | 39,112 | 0.00 (−0.02 to 0.02) | 0.96 | 1.0 × 10−12 | ||
| ln triglycerides | 68,777 | 0.33 (0.31–0.35) | 4.3 × 10−224 | 34,061 | 0.27 (0.25–0.29) | 9.4 × 10−181 | 2.4 × 10−5 | ||
| ln ALT | 27,956 | 0.24 (0.18–0.30) | 1.1 × 10−13 | 17,517 | 0.19 (0.17–0.21) | 3.1 × 10−69 | 0.2 | ||
| ln GGT | 47,202 | 0.25 (0.22–0.28) | 4.5 × 10−50 | 24,657 | 0.18 (0.16–0.20) | 4.5 × 10−65 | 5.5 × 10−4 | ||
| IV analyses | |||||||||
| Diastolic blood pressure | 35,518 | 0.21 (0.09–0.33) | 8.0 × 10−4 | 0.20 | 32,596 | 0.01 (−0.16 to 0.18) | 0.93 | 0.01 | 0.06 |
| Systolic blood pressure | 35,681 | 0.21 (0.12–0.30) | 2.5 × 10−6 | 0.41 | 32,989 | 0.06 (−0.14 to 0.26) | 0.56 | 0.13 | 0.17 |
| Fasting glucose | 20,742 | 0.10 (−0.01 to 0.22) | 0.09 | 0.29 | 17,380 | 0.04 (−0.11 to 0.19) | 0.58 | 0.01 | 0.54 |
| 2-h post-OGTT glucose | 2,077 | −0.01 (−0.41 to 0.39) | 0.97 | 0.38 | 2,519 | 0.13 (−0.27 to 0.53) | 0.53 | 0.71 | 0.64 |
| HbA1c | 13,614 | 0.10 (−0.05 to 0.24) | 0.19 | 0.65 | 13,287 | 0.25 (0.01–0.48) | 0.04 | 0.58 | 0.29 |
| ln fasting insulin | 15,985 | 0.26 (0.10–0.42) | 0.001 | 0.01 | 9,526 | 0.32 (0.12–0.52) | 0.002 | 0.09 | 0.64 |
| ln CRP | 25,822 | 0.35 (0.23–0.48) | 7.5 × 10−8 | 0.48 | 21,943 | 0.18 (0.01–0.35) | 0.04 | 0.17 | 0.10 |
| ln IL-6 | 5,368 | 0.37 (0.12–0.61) | 0.004 | 0.13 | 4,917 | 0.13 (−0.13 to 0.40) | 0.32 | 0.96 | 0.21 |
| HDL-C | 32,977 | −0.36 (−0.47 to −0.25) | 3.4 × 10−10 | 0.20 | 26,425 | −0.28 (−0.40 to −0.17) | 1.2 × 10−6 | 0.97 | 0.36 |
| LDL-C | 32,016 | 0.15 (0.05–0.25) | 0.004 | 0.92 | 21,851 | −0.10 (−0.32 to 0.12) | 0.38 | 0.30 | 0.04 |
| Total cholesterol | 33,002 | 0.10 (−0.05 to 0.24) | 0.20 | 0.73 | 27,344 | −0.19 (−0.36 to −0.01) | 0.04 | 0.04 | 0.015 |
| ln triglycerides | 33,018 | 0.28 (0.16–0.41) | 1.3 × 10−5 | 0.45 | 22,438 | 0.12 (0.00–0.25) | 0.05 | 0.02 | 0.09 |
| ln ALT | 11,215 | 0.22 (0.05–0.39) | 0.01 | 0.84 | 12,712 | −0.10 (−0.39 to 0.19) | 0.50 | 0.05 | 0.06 |
| ln GGT | 13,915 | 0.24 (0.10–0.38) | 0.001 | 0.87 | 12,916 | −0.01 (−0.24 to 0.21) | 0.92 | 0.10 | 0.07 |
All models were adjusted for sex and age. β (95% CI), effect per SD change of BMI on trait (SD scale); Pdiff, difference between the two strata (only significant P values are shown); PIV-obs, P value from test of difference between observational and IV analyses.
*A nominal P value of <0.022 is considered significant at a 5% FDR level.