Table 1.
Unweighted and weighted genetic risk scores - trait associations at baseline (Nmax=2,585)
| Trait (units) | GRS | N | β | SE | P | 95% CI LL |
95% CI UL |
PwGRS | β inv | SEinv | Pinv | PwGRSinv |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ApoB (g/l) | ApoB GRS | 2,567 | 0.014 | 0.002 | 1.9E-10 | 0.01 | 0.018 | 2.2E-25 | 0.058 | 0.009 | 8.0E-11 | 4.3E-26 |
| ApoB (g/l) | LDL-C GRS | 2,567 | 0.007 | 0.001 | 2.8E-11 | 0.005 | 0.009 | 1.4E-14 | 0.03 | 0.004 | 1.9E-11 | 4.0E-15 |
| ApoB (g/l) | TC GRS | 2,567 | 0.006 | 0.001 | 4.2E-12 | 0.005 | 0.008 | 1.6E-18 | 0.027 | 0.004 | 2.1E-12 | 6.5E-19 |
| HDL size (nm) |
HDL size GRS |
1,714 | −0.018 | 0.004 | 1.3E-05 | −0.026 | −0.01 | 5.7E-08 | −0.04 | 0.01 | 8.6E-05 | 6.4E-07 |
| HDL-C (mmol/l) |
HDL-C GRS | 2,584 | −0.007 | 0.001 | 1.9E-12 | −0.01 | −0.005 | 4.2E-31 | −0.027 | 0.003 | 1.6E-14 | 1.8E-36 |
| IDL-C (nmol/l) |
IDL-C GRS | 1,710 | −1.568 | 1.409 | 2.7E-01 | −4.332 | 1.197 | 4.6E-01 | −0.011 | 0.013 | 4.1E-01 | 4.4E-01 |
| large HDL (μmol/l) |
HDL-C GRS | 1,712 | −0.052 | 0.01 | 5.6E-07 | −0.073 | −0.032 | 6.6E-15 | −0.023 | 0.004 | 4.8E-08 | 4.4E-16 |
| large HDL (μmol/l) |
large HDL GRS |
1,712 | −0.151 | 0.026 | 5.7E-09 | −0.202 | −0.1 | 4.9E-13 | −0.06 | 0.01 | 6.2E-09 | 1.2E-12 |
| large LDL (nmol/l) |
HDL-C GRS | 1,632 | −4.903 | 1.152 | 2.2E-05 | −7.162 | −2.644 | 4.2E-12 | −0.021 | 0.005 | 7.2E-06 | 4.4E-13 |
| large LDL (nmol/l) |
large LDL GRS |
1,632 | 13.644 | 2.257 | 1.8E-09 | 9.217 | 18.072 | 8.8E-12 | 0.053 | 0.009 | 4.4E-09 | 6.0E-11 |
| large VLDL (nmol/l) |
large VLDL GRS |
1,714 | 0.353 | 0.088 | 6.9E-05 | 0.179 | 0.526 | 1.5E-04 | 0.049 | 0.012 | 2.4E-05 | 1.7E-05 |
| large VLDL (nmol/l) |
TG GRS | 1,714 | 0.261 | 0.045 | 9.3E-09 | 0.172 | 0.349 | 2.0E-17 | 0.035 | 0.006 | 3.5E-09 | 2.4E-18 |
| LDL size (nm) |
HDL-C GRS | 2,585 | −0.073 | 0.011 | 1.7E-11 | −0.094 | −0.052 | 1.7E-16 | −0.023 | 0.004 | 1.1E-10 | 9.6E-16 |
| LDL size (nm) |
LDL size GRS |
2,585 | 0.172 | 0.023 | 5.2E-14 | 0.127 | 0.216 | 2.8E-12 | 0.055 | 0.008 | 6.8E-13 | 1.2E-11 |
| LDL size (nm) |
TG GRS | 2,585 | −0.119 | 0.015 | 2.8E-15 | −0.149 | −0.09 | 5.3E-18 | −0.039 | 0.005 | 5.8E-15 | 7.1E-18 |
| LDL-C (mmol/l) |
LDL-C GRS | 2,584 | 0.027 | 0.004 | 1.4E-12 | 0.02 | 0.034 | 4.2E-18 | 0.032 | 0.004 | 7.7E-13 | 2.6E-18 |
| medium HDL (μmol/l) |
medium HDL GRS |
1,714 | −0.045 | 0.077 | 5.6E-01 | −0.196 | 0.105 | 4.0E-01 | −0.009 | 0.014 | 5.4E-01 | 4.0E-01 |
| medium VLDL (nmol/l) |
medium VLDL GRS |
1,707 | 1.113 | 0.236 | 2.5E-06 | 0.651 | 1.575 | 6.5E-03 | 0.056 | 0.012 | 1.3E-06 | 7.3E-03 |
| medium VLDL (nmol/l) |
TG GRS | 1,707 | 0.483 | 0.123 | 9.1E-05 | 0.241 | 0.725 | 1.1E-11 | 0.024 | 0.006 | 5.6E-05 | 5.0E-12 |
| small HDL (μmol/l) |
small HDL GRS |
1,713 | −0.366 | 0.056 | 6.2E-11 | −0.475 | −0.257 | 6.8E-19 | −0.076 | 0.012 | 7.9E-11 | 9.6E-19 |
| small LDL (nmol/l) |
HDL-C GRS | 1,714 | 8.772 | 1.793 | 1.1E-06 | 5.256 | 12.289 | 1.2E-11 | 0.022 | 0.004 | 6.3E-07 | 6.4E-12 |
| small LDL (nmol/l) |
small LDL GRS |
1,714 | 26.807 | 4.017 | 3.4E-11 | 18.929 | 34.685 | 1.2E-09 | 0.067 | 0.01 | 3.2E-11 | 1.3E-09 |
| small VLDL (nmol/l) |
small VLDL GRS |
1,708 | 0.83 | 0.182 | 5.6E-06 | 0.473 | 1.187 | 6.3E-08 | 0.045 | 0.01 | 1.6E-05 | 2.0E-07 |
| TC (mmol/l) |
TC GRS | 2,584 | 0.029 | 0.004 | 2.4E-16 | 0.022 | 0.036 | 2.2E-24 | 0.031 | 0.004 | 2.1E-16 | 2.2E-24 |
| TG (mmol/l) |
TG GRS | 2,584 | 0.043 | 0.005 | 2.5E-15 | 0.033 | 0.054 | 6.0E-24 | 0.041 | 0.005 | 1.1E-16 | 1.7E-26 |
| total HDL (μmol/l) |
HDL-C GRS | 1,711 | −0.051 | 0.027 | 5.7E-02 | −0.103 | 0.002 | 1.2E-04 | −0.01 | 0.004 | 2.8E-02 | 4.4E-05 |
| total HDL (μmol/l) |
total HDL GRS |
1,711 | −0.517 | 0.094 | 4.7E-08 | −0.702 | −0.332 | 1.6E-10 | −0.087 | 0.015 | 1.9E-08 | 7.0E-11 |
| total LDL (nmol/l) |
LDL-C GRS | 1,714 | 9.782 | 2.064 | 2.3E-06 | 5.734 | 13.829 | 5.0E-08 | 0.027 | 0.005 | 9.9E-07 | 3.0E-08 |
| total LDL (nmol/l) |
TC GRS | 1,714 | 8.442 | 1.786 | 2.5E-06 | 4.94 | 11.945 | 3.9E-09 | 0.023 | 0.005 | 1.1E-06 | 1.7E-09 |
| total LDL (nmol/l) |
total LDL GRS |
1,714 | 14.083 | 3.67 | 1.3E-04 | 6.884 | 21.281 | 3.1E-08 | 0.037 | 0.01 | 1.1E-04 | 2.9E-08 |
| total VLDL (nmol/l) |
TG GRS | 1,714 | 0.885 | 0.205 | 1.6E-05 | 0.483 | 1.286 | 3.8E-11 | 0.026 | 0.006 | 1.7E-05 | 5.4E-11 |
| total VLDL (nmol/l) |
total VLDL GRS |
1,714 | 2.467 | 0.362 | 1.3E-11 | 1.757 | 3.177 | 1.2E-08 | 0.072 | 0.011 | 1.1E-11 | 1.5E-08 |
| VLDL size (nm) |
TG GRS | 1,648 | 0.255 | 0.054 | 2.4E-06 | 0.149 | 0.361 | 1.4E-11 | 0.029 | 0.006 | 8.0E-06 | 5.8E-11 |
| VLDL size (nm) |
VLDL size GRS |
1,648 | 0.579 | 0.131 | 1.0E-05 | 0.323 | 0.835 | 9.5E-08 | 0.066 | 0.015 | 1.9E-05 | 1.6E-07 |
95% CI LL - 95% confidence interval lower limit; 95% CI UL - 95% confidence interval upper limit; ApoB - apolipoprotein B; β - beta effect estimate; βinv – beta effect estimate for inverse normalized traits; DPP - Diabetes Prevention Program; GRS - genetic risk score per GRS risk allele; HDL - high density lipoprotein; IDL - intermediate density lipoprotein; inv – inverse normalized traits; LDL - low density lipoprotein; N - sample size; Pinv – P value for inverse normalized traits; PwGRS – P value for weighted genetic risk score associations; PwGRSinv – P value for weighted genetic risk score associations undertaken with the inverse normalized traits; SE - standard error; SEinv – standard error for inverse normalized traits; TC - total cholesterol; TG - triglyceride; VLDL - very low density lipoprotein; wGRS - weighted genetic risk score.
P values are based on linear regression models. SNP associations were tested by fitting the genetic risk scores as the independent variables with the different lipoprotein subfractions at baseline as dependent variables. β coefficients reflect the association of one genetic risk score unit (effect allele) with the trait (expressed in native units and inverse normalized units).
Age, age2, sex and genomic principal components were used as covariates in all models.