Table 4.
Associations Between BMI/FMI and FT3 and FT4 Levels at Age 7 as Tested Both by Conventional Epidemiological Approaches and Through the Application of Instrumental Variable Analyses
| Adiposity | Model | n | Linear Regression |
Instrumental Variable Regression (Weighted Allelic Score With 31 SNPs) |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| B (95% CI) | β-(std) (95% CI) | P Value | F-Statistic | Partial R2 | B (95% CI) | β-(std) (95% CI)a | P Value | P Value (DWH) | |||
| 31 SNPs (all SNPs excluding FTO) | |||||||||||
| FT3 age 7 | |||||||||||
| BMI (kg/m2) | Model 1 | 3014 | 0.05 (0.04, 0.06) | 0.13 (0.10, 0.16) | 5.30 × 10−16 | 73.6 | 0.008 | 0.19 (0.04, 0.33) | 0.30 (0.07, 0.53) | .01 | .17 |
| Age 7 | Model 2 | 3014 | 0.05 (0.04, 0.06) | 0.16 (0.13, 0.19) | 6.61 × 10−21 | 75.1 | 0.10 | 0.19 (0.05, 0.32) | 0.30 (0.08, 0.52) | .007 | .21 |
| Model 3a | 2538 | 0.04 (0.03, 0.05) | 0.12 (0.08, 0.16) | 3.08 × 10−13 | 57.9 | 0.07 | 0.20 (0.03, 0.38) | 0.33 (0.04, 0.61) | .02 | .14 | |
| FMI (kg/m2)a | Model 1 | 3014 | 0.22 (0.17, 0.27) | 0.17 (0.13, 0.20) | 1.56 × 10−22 | 98.1 | 0.04 | 0.16 (0.04, 0.29) | 0.26 (0.06, 0.46) | .01 | .45 |
| Age 9 | Model 2 | 3014 | 0.23 (0.19, 0.27) | 0.19 (0.16, 0.23) | 2.16 × 10−18 | 98.6 | 0.12 | 0.17 (0.05, 0.28) | 0.27 (0.08, 0.46) | .06 | .43 |
| Model 3a | 2538 | 0.17 (0.12, 0.22) | 0.13 (0.09, 0.17) | 3.59 × 10−18 | 77.6 | 0.10 | 0.17 (0.03, 0.32) | 0.28 (0.04, 0.51) | .02 | .26 | |
| FT4 age 7 | |||||||||||
| BMI (kg/m2) | Model 1 | 3014 | −0.07 (−0.10, −0.03) | −0.05 (−0.08, −0.02) | .001 | 71.9 | 0.01 | 0.03 (−0.35, 0.41) | 0.02 (−0.21, 0.25) | .88 | .51 |
| Age 7 | Model 2 | 3014 | −0.12 (−0.16, −0.08) | −0.10 (−0.13, −0.06) | 1.64 × 10−08 | 69.9 | 0.11 | −0.14 (−0.51, 0.23) | −0.09 (−0.31, 0.14) | .46 | .90 |
| Model 3a | 2538 | −0.09 (−0.14, −0.05) | −0.08 (−0.12, −0.04) | .00003 | 48.7 | 0.10 | −0.06 (−0.54 0.41) | −0.04 (−0.33, 0.25) | .79 | .79 | |
| FMI (kg/m2)a | Model 1 | 3014 | −0.01 (−0.02, −0.001) | −0.04 (−0.07, −0.002) | .04 | 105 | 0.01 | −0.003 (−0.33, 0.32) | −0.01 (−0.20, 0.20) | .99 | .70 |
| Age 9 | Model 2 | 3014 | −0.03 (−0.04, −0.02) | −0.09 (−0.13, −0.06) | 2.42 × 10−07 | 103 | 0.11 | −0.16 (−0.49, 0.17) | −0.10 (−0.29, 0.10) | .35 | .99 |
| Model 3a | 2538 | −0.02 (−0.03, −0.01) | −0.07 (−0.11, −0.03) | .002 | 74.2 | 0.10 | −0.05 (−0.45, 0.35) | −0.03 (−0.27, 0.21) | .80 | .70 | |
| FTO SNP alone | |||||||||||
| FT3 age 7 | |||||||||||
| BMI (kg/m2) | Model 1 | 3014 | 0.05 (0.04, 0.06) | 0.13 (0.10, 0.16) | 5.30 × 10−16 | 10.6 | 0.64 | 0.61 (0.12, 1.09) | 0.97 (0.20, 1.75) | .01 | .006 |
| Age 7 | Model 2 | 3014 | 0.05 (0.04, 0.06) | 0.16 (0.13, 0.19) | 6.61 × 10−21 | 11.8 | 0.61 | 0.63 (0.15, 1.11) | 1.02 (0.25, 21.80) | .01 | .003 |
| Model 3a | 2538 | 0.04 (0.03, 0.05) | 0.12 (0.08, 0.16) | 3.08 × 10−13 | 9.52 | 0.67 | 0.72 (0.02, 1.43) | 1.17 (0.03, 2.30) | .04 | .007 | |
| FMI (kg/m2) | Model 1 | 3014 | 0.22 (0.17, 0.27) | 0.17 (0.13, 0.20) | 1.56 × 10−22 | 9.87 | 0.31 | 0.48 (0.14, 0.82) | 0.78 (0.23, 1.32) | .006 | .01 |
| Age 9 | Model 2 | 3014 | 0.23 (0.19, 0.27) | 0.19 (0.16, 0.23) | 2.16 × 10−78 | 15.9 | 0.26 | 0.50 (0.17, 0.84) | 0.82 (0.28, 1.36) | .003 | .008 |
| Model 3a | 2538 | 0.17 (0.12, 0.22) | 0.13 (0.09, 0.17) | 3.59 × 10−18 | 14.6 | 0.24 | 0.52 (0.10, 0.94) | 0.84 (0.16, 1.52) | .008 | .02 | |
| FT4 age 7 | |||||||||||
| BMI (kg/m2) | Model 1 | 3014 | −0.07 (−0.10, −0.03) | −0.05 (−0.08, −0.02) | .001 | 10.6 | 0.01 | −0.21 (−1.20, 0.79) | −0.13 (−0.73, 0.47) | .68 | .82 |
| Age 7 | Model 2 | 3014 | −0.12 (−0.16, −0.08) | −0.10 (−0.13, −0.06) | 1.64 × 10−08 | 7.95 | 0.02 | −0.77 (−1.96, 0.41) | −0.47 (−1.18, 0.25) | .20 | .28 |
| Model 3a | 2538 | −0.09 (−0.14, −0.05) | −0.08 (−0.12, −0.04) | .00003 | 5.27 | 0.01 | −0.68 (−2.16, 0.83) | −0.41 (−1.33, 0.50) | .37 | .45 | |
| FMI (kg/m2) | Model 1 | 3014 | −0.01 (−0.02, −0.001) | −0.04 (−0.07, −0.002) | .04 | 18.1 | 0.01 | −0.20 (−1.00, 0.60) | −0.12 (−0.61, 0.31 | .63 | .74 |
| Age 9 | Model 2 | 3014 | −0.03 (−0.04, −0.02) | −0.09 (−0.13, −0.06) | 2.42 × 10−07 | 14.2 | 0.03 | −0.65 (−1.56, 0.26) | −0.39 (−0.94, 0.16) | .16 | .27 |
| Model 3a | 2538 | −0.02 (−0.03, −0.01) | −0.07 (−0.11, −0.03) | .002 | 11.2 | 0.07 | −0.50 (−1.55, 0.56) | −0.30 (−0.93, 0.35) | .36 | .49 | |
P (DWH) is the P value of the Durbin form of the DWH test, which examines the difference between the estimates from linear regression and instrumental variable analysis. Model 1 adjusted for age and sex; model 2 adjusted for model 1 and other thyroid hormone parameters; model 3 adjusted for model 2 and height markers of social class and early life environment (home ownership, maternal age at birth of child, maternal highest educational qualification, maternal smoking in pregnancy, family adversity index, and parents and home score). B, β-coefficient; P, strength of evidence against the null hypothesis of no association.
A total of 476 individuals with missing data.