Table 5. Interaction between obesity SNPs or GRS and glycemic transition on baseline BMI and change in BMI.
| Gene | SNP | Risk Allele | SNP Main effectb | NGT to IFG/IGT Interaction | NGT to T2D Interaction | IFG/IGT to T2D Interaction | Change in FPG Interaction | Change in 2hPG Interaction |
|---|---|---|---|---|---|---|---|---|
| BMI AT BASELINE | ||||||||
| APOE | rs2075650 | G | 0.01 ± 0.02 (0.15) | 0.003 ± 0.081 (0.97) | 0.06 ± 0.15 (0.69) | −0.09 ± 0.06 (0.14) | 0.0002 ± 0.0194 (0.99) | −0.01 ± 0.02 (0.54) |
| BDNF | rs6265 | C | 0.02 ± 0.01 (0.19) | −0.04 ± 0.07 (0.53) | 0.06 ± 0.16 (0.68) | −0.07 ± 0.05 (0.21) | −0.01 ± 0.02 (0.51) | 0.005 ± 0.019 (0.81) |
| BDNF | rs1401635 | G | 0.02 ± 0.01 (0.11) | −0.10 ± 0.06 (8.3 × 10−2) | −0.02 ± 0.12 (0.84) | −0.05 ± 0.05 (0.30) | −0.004 ± 0.014 (0.79) | 0.001 ± 0.016 (0.94) |
| CDKAL1 | rs2206734 | C | 0.04 ± 0.01 (3.9 × 10−3) | –0.02 ± 0.07 (0.72) | −0.12 ± 0.14 (0.37) | −0.03 ± 0.05 (0.57) | −0.03 ± 0.02 (4.8 × 10−2) | 0.001 ± 0.018 (0.93) |
| FANCL | rs12617233 | C | 0.01 ± 0.01 (0.28) | 0.01 ± 0.05 (0.80) | −0.01 ± 0.11 (0.91) | −0.07 ± 0.04 (0.10) | −0.01 ± 0.01 (0.29) | 0.01 ± 0.01 (0.50) |
| FTO | rs7203521 | A | 0.01 ± 0.01 (0.48) | 0.04 ± 0.05 (0.38) | 0.05 ± 0.10 (0.62) | 0.05 ± 0.04 (0.27) | 0.01 ± 0.01 (0.39) | −0.01 ± 0.01 (0.58) |
| FTO | rs9939609 | A | 0.08 ± 0.01 (1.4 × 10−14) | 0.04 ± 0.05 (0.44) | −0.01 ± 0.11 (0.94) | 0.06 ± 0.04 (0.15) | 0.03 ± 0.01 (4.8 × 10−2) | −0.001 ± 0.015 (0.97) |
| GIPR | rs11671664 | G | 0.03 ± 0.02 (0.11) | 0.05 ± 0.09 (0.57) | −0.03 ± 0.18 (0.85) | −0.02 ± 0.06 (0.78) | −0.01 ± 0.02 (0.54) | −0.005 ± 0.023 (0.84) |
| ITIH4 | rs2535633 | G | −0.002 ± 0.015 (0.13) | −0.004 ± 0.052 (0.94) | −0.07 ± 0.11 (0.52) | −0.0004 ± 0.0427 (0.99) | −0.01 ± 0.01 (0.52) | 0.01 ± 0.01 (0.53) |
| KAT8 | rs749767 | A | 0.01 ± 0.01 (0.39) | 0.01 ± 0.05 (0.80) | 0.04 ± 0.11 (0.75) | 0.05 ± 0.04 (0.25) | 0.002 ± 0.013 (0.89) | −0.01 ± 0.01 (0.34) |
| LEPR | rs1011527 | A | −0.01 ± 0.02 (0.72) | −0.10 ± 0.08 (0.17) | −0.30 ± 0.16 (6.4 × 10−2) | −0.14 ± 0.06 (3.3 × 10−2) | 0.03 ± 0.02 (0.11) | −0.01 ± 0.02 (0.74) |
| MAPK25 | rs997295 | T | 0.01 ± 0.02 (0.41) | 0.02 ± 0.05 (0.73) | 0.15 ± 0.11 (0.17) | −0.04 ± 0.04 (0.38) | 0.01 ± 0.01 (0.62) | −0.01 ± 0.01 (0.68) |
| NPC1 | rs1805081 | A | 0.02 ± 0.01 (0.15) | −0.02 ± 0.05 (0.72) | −0.09 ± 0.12 (0.44) | 0.01 ± 0.04 (0.87) | 0.004 ± 0.014 (0.78) | −0.01 ± 0.02 (0.46) |
| NT5C2 | rs3824755 | C | 0.03 ± 0.01 (3.5 × 10−2) | −0.11 ± 0.07 (0.12) | −0.23 ± 0.14 (9.7 × 10−2) | −0.01 ± 0.06 (0.88) | 0.01 ± 0.02 (0.71) | −0.03 ± 0.02 (0.11) |
| NTRK2 | rs1211166 | A | 0.01 ± 0.01 (0.28) | −0.11 ± 0.06 (8.2 × 10−2) | 0.11 ± 0.14 (0.43) | 0.03 ± 0.05 (0.05) | 0.01 ± 0.02 (0.58) | 0.02 ± 0.02 (0.16) |
| PCSK1 | rs6232 | C | 0.02 ± 0.03 (0.32) | 0.01 ± 0.13 (0.93) | −0.36 ± 0.29 (0.21) | −0.13 ± 0.10 (0.20) | 0.04 ± 0.03 (0.25) | −0.03 ± 0.03 (0.44) |
| PCSK1 | rs6235 | G | 0.002 ± 0.012 (0.85) | 0.06 ± 0.06 (0.27) | −0.12 ± 0.12 (0.31) | 0.04 ± 0.05 (0.44) | 0.004 ± 0.015 (0.78) | 0.001 ± 0.017 (0.97) |
| POMC | rs7605927 | G | −0.01 ± 0.01 (0.24) | −0.03 ± 0.05 (0.52) | −0.03 ± 0.12 (0.77) | 0.004 ± 0.044 (0.93) | 0.02 ± 0.01 (0.17) | −0.0004 ± 0.0153 (0.98) |
| TAL1 | rs2984618 | T | 0.04 ± 0.01 (1.8 × 10−5) | −0.05 ± 0.05 (0.28) | −0.11 ± 0.11 (0.32) | −0.04 ± 0.04 (0.38) | −0.004 ± 0.013 (0.76) | −0.01 ± 0.01 (0.36) |
| TCF7L2 | rs7903146 | C | 0.05 ± 0.01 (1.7 × 10−6) | 0.04 ± 0.06 (0.47) | −0.04 ± 0.11 (0.70) | 0.01 ± 0.04 (0.75) | −0.01 ± 0.01 (0.60) | −0.02 ± 0.02 (0.16) |
| TFAP2B | rs2272903 | G | 0.02 ± 0.01 (0.13) | 0.09 ± 0.07 (0.19) | 0.11 ± 0.14 (0.46) | 0.08 ± 0.06 (0.20) | 0.004 ± 0.018 (0.83) | −0.005 ± 0.021 (0.83) |
| TNN13K | rs1514176 | G | 0.03 ± 0.01 (5.6 × 10−3) | 0.01 ± 0.05 (0.85) | −0.23 ± 0.11 (3.0 × 10−2) | 0.001 ± 0.042 (0.99) | 0.01 ± 0.01 (0.28) | −0.01 ± 0.01 (0.49) |
| USP37 | rs611203 | G | −0.002 ± 0.010 (0.83) | 0.01 ± 0.05 (0.87) | 0.06 ± 0.11 (0.56) | 0.01 ± 0.04 (0.78) | 0.003 ± 0.014 (0.85) | 0.002 ± 0.014 (0.85) |
| Genotype score | 0.018 ± 0.002 (6.4 × 10−14) | −0.004 ± 0.012 (0.73) | −0.03 ± 0.03 (0.19) | −0.004 ± 0.009 (0.69) | 0.003 ± 0.003 (0.35) | −0.004 ± 0.003 (0.26) | ||
| CHANGE IN BMIa | ||||||||
| APOE | rs2075650 | G | −0.01 ± 0.02 (0.56) | 0.07 ± 0.09 (0.42) | −0.06 ± 0.18 (0.73) | 0.13 ± 0.07 (8.9 × 10−2) | 0.05 ± 0.02 (3.3 × 10−2) | 0.03 ± 0.02 (0.19) |
| BDNF | rs6265 | C | 0.01 ± 0.02 (0.48) | −0.08 ± 0.07 (0.27) | −0.24 ± 0.17 (0.16) | 0.13 ± 0.06 (3.4 × 10−2) | 0.03 ± 0.01 (7.8 × 10−2) | 0.04 ± 0.02 (7.2 × 10−2) |
| BDNF | rs1401635 | G | 0.02 ± 0.02 (0.16) | −0.09 ± 0.06 (0.16) | −0.02 ± 0.14 (0.89) | −0.01 ± 0.05 (0.87) | −0.01 ± 0.02 (0.43) | 0.02 ± 0.02 (0.15) |
| CDKAL1 | rs2206734 | C | −0.05 ± 0.02 (3.4 × 10−3) | −0.01 ± 0.07 (0.92) | −0.13 ± 0.16 (0.43) | 0.02 ± 0.06 (0.73) | −0.02 ± 0.02 (0.34) | 0.0002 ± 0.0193 (0.99) |
| FANCL | rs12617233 | C | −0.03 ± 0.01 (2.8 × 10−2) | −0.03 ± 0.06 (0.55) | 0.10 ± 0.12 (0.42) | −0.04 ± 0.05 (0.39) | −0.01 ± 0.02 (0.70) | −0.03 ± 0.02 (8.9 × 10−2) |
| FTO | rs7203521 | A | 0.01 ± 0.01 (0.64) | 0.03 ± 0.05 (0.53) | 0.07 ± 0.12 (0.59) | 0.09 ± 0.05 (7.4 × 10−2) | 0.01 ± 0.02 (0.41) | 0.01 ± 0.02 (0.46) |
| FTO | rs9939609 | A | −0.0001 ± 0.0150 (0.99) | −0.02 ± 0.06 (0.70) | −0.10 ± 0.12 (0.42) | −0.06 ± 0.05 (0.20) | −0.02 ± 0.01 (0.20) | −0.03 ± 0.02 (0.11) |
| GIPR | rs11671664 | G | −0.001 ± 0.024 (0.95) | 0.07 ± 0.09 (0.46) | −0.30 ± 0.21 (0.15) | 0.02 ± 0.08 (0.82) | 0.01 ± 0.02 (0.54) | −0.01 ± 0.03 (0.58) |
| ITIH4 | rs2535633 | G | 0.003 ± 0.015 (0.83) | 0.09 ± 0.06 (9.5 × 10−2) | 0.22 ± 0.12 (6.9 × 10−2) | −0.04 ± 0.05 (0.40) | 0.01 ± 0.01 (0.33) | 0.03 ± 0.02 (3.4 × 10−2) |
| KAT8 | rs749767 | A | 0.01 ± 0.02 (0.35) | −0.05 ± 0.06 (0.34) | −0.22 ± 0.13 (0.10) | −0.05 ± 0.05 (0.36) | −0.01 ± 0.01 (0.45) | 0.002 ± 0.016 (0.92) |
| LEPR | rs1011527 | A | −0.02 ± 0.02 (0.41) | −0.14 ± 0.09 (0.11) | 0.03 ± 0.18 (0.85) | 0.05 ± 0.08 (0.52) | −0.03 ± 0.02 (0.21) | −0.02 ± 0.03 (0.51) |
| MAPK25 | rs997295 | T | 0.002 ± 0.015 (0.99) | 0.05 ± 0.05 (0.35) | 0.09 ± 0.12 (0.46) | −0.02 ± 0.05 (0.75) | 0.02 ± 0.01 (0.15) | 0.02 ± 0.02 (0.26) |
| NPC1 | rs1805081 | A | 0.003 ± 0.016 (0.83) | −0.04 ± 0.06 (0.44) | 0.08 ± 0.14 (0.58) | −0.08 ± 0.05 (0.13) | −0.001 ± 0.016 (0.96) | −0.01 ± 0.02 (0.40) |
| NT5C2 | rs3824755 | C | 0.02 ± 0.02 (0.31) | −0.07 ± 0.08 (0.36) | −0.07 ± 0.16 (0.64) | 0.01 ± 0.07 (0.85) | −0.02 ± 0.02 (0.44) | 0.01 ± 0.02 (0.73) |
| NTRK2 | rs1211166 | A | −0.002 ± 0.018 (0.92) | −0.03 ± 0.07 (0.68) | 0.07 ± 0.16 (0.65) | −0.04 ± 0.06 (0.48) | 0.03 ± 0.02 (9.3 × 10−2) | −0.02 ± 0.02 (0.38) |
| PCSK1 | rs6232 | C | −0.03 ± 0.04 (0.49) | 0.28 ± 0.14 (4.9 × 10−2) | 0.44 ± 0.31 (0.15) | −0.07 ± 0.12 (0.57) | −0.06 ± 0.04 (0.12) | −0.02 ± 0.04 (0.64) |
| PCSK1 | rs6235 | G | −0.002 ± 0.017 (0.93) | 0.07 ± 0.06 (0.24) | −0.04 ± 0.13 (0.77) | −0.06 ± 0.06 (0.26) | −0.003 ± 0.017 (0.86) | −0.01 ± 0.02 (0.51) |
| POMC | rs7605927 | G | −0.01 ± 0.02 (0.51) | 0.02 ± 0.06 (0.75) | 0.05 ± 0.13 (0.70) | 0.01 ± 0.05 (0.87) | −0.01 ± 0.02 (0.57) | 0.001 ± 0.017 (0.93) |
| TAL1 | rs2984618 | T | −0.01 ± 0.01 (0.38) | 0.05 ± 0.05 (0.32) | 0.05 ± 0.13 (0.70) | −0.04 ± 0.05 (0.36) | −0.02 ± 0.01 (0.20) | 0.01 ± 0.02 (0.35) |
| TCF7L2 | rs7903146 | C | 0.02 ± 0.02 (0.20) | −0.003 ± 0.062 (0.97) | 0.19 ± 0.13 (0.15) | −0.06 ± 0.05 (0.21) | −0.01 ± 0.02 (0.35) | 0.001 ± 0.017 (0.97) |
| TFAP2B | rs2272903 | G | −0.03 ± 0.02 (0.13) | 0.11 ± 0.08 (0.17) | −0.004 ± 0.160 (0.98) | 0.09 ± 0.07 (0.22) | 0.02 ± 0.02 (0.29) | −0.002 ± 0.023 (0.92) |
| TNN13K | rs1514176 | G | −0.02 ± 0.01 (0.29) | 0.10 ± 0.05 (6.0 × 10−2) | 0.15 ± 0.12 (0.22) | −0.03 ± 0.05 (0.55) | 0.02 ± 0.01 (0.14) | 0.01 ± 0.02 (0.53) |
| USP37 | rs611203 | G | −0.02 ± 0.01 (0.24) | 0.04 ± 0.06 (0.50) | −0.12 ± 0.12 (0.33) | 0.01 ± 0.05 (0.89) | 0.02 ± 0.01 (0.19) | −0.002 ± 0.016 (0.88) |
| Genotype score | −0.004 ± 0.003 (0.24) | 0.01 ± 0.01 (0.37) | 0.01 ± 0.03 (0.65) | −0.01 ± 0.01 (0.41) | 0.003 ± 0.003 (0.34) | 0.002 ± 0.004 (0.49) | ||
Data are indicated as B ± SE (P). Adjusted for sex, age, population stratification/ethnicity and arandomization to thiazolidinedione after baseline. P < 4.1 × 10−4 (0.05/120) are statistically significant interactions. P < 2.1 × 10−3 (0.05/24) are statistically significant main effects (without interaction term in model)b. Genotype score was calculated by summing the alleles predisposing to increased BMI/obesity for the 23 SNPs.