Table 1.
Application to DCCT/EDIC genetics study: Regression analysis and gene‐based analysis results for association of the HDL trait with 10 SNPS in the CETP gene
| Regression Analysis Results | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Joint Analysis | Marginal Analysis | |||||||||
| SNP | rs ID | bp Position | Cluster Allocation | MAF | Beta | P‐Value | LC‐B per Cluster | Wald per Cluster | Beta | P‐Value |
| SNP1 | rs17245715 | 56961078 | 1 | 0.082 | –0.040 | 0.075 | 0.17 | 5.56 | 0.006 | 0.709 |
| SNP8 | rs12720898 | 56977331 | 1 | 0.068 | 0.048 | 0.058 | (P = 0.682) | (P = 0.135) | 0.037 | 0.043 |
| SNP10 | rs1801706 | 56983750 | 1 | 0.166 | –0.018 | 0.556 | 0.014 | 0.262 | ||
| SNP3 | rs708273 | 56966037 | 2 | 0.299 | 0.001 | 0.985 | 0.372 | 0.482 | –0.012 | 0.230 |
| SNP6 | rs289717 | 56975476 | 2 | 0.347 | –0.011 | 0.497 | (P = 0.542) | (P = 0.786) | –0.012 | 0.206 |
| SNP4 | rs12720922 | 56966973 | 3 | 0.173 | –0.063 | 0.001 | 10.5 | 12.6 | –0.080 | 4.33 × 10−11 |
| SNP5 | rs11076176 | 56973534 | 3 | 0.193 | –0.008 | 0.767 | (P = 0.001) | (P=5.00 × 10−8) | –0.067 | 5.34 × 10−9 |
| SNP7 | rs736274 | 56975857 | 4 | 0.109 | 0.011 | 0.690 | 0.789 | 0.813 | 0.045 | 0.002 |
| SNP9 | rs5882 | 56982180 | 4 | 0.304 | 0.003 | 0.893 | (P = 0.374) | (P = 0.666) | 0.032 | 0.001 |
| SNP2 | rs3816117 | 56962246 | 5 | 0.469 | 0.035 | 0.173 | 1.86 | 1.86 | 0.055 | 1.45 × 10−9 |
| (P = 0.172) | (P = 0.172) | |||||||||
| Gene‐Based Analysis Results | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Joint Analysis | Marginal Analysis | |||||||||||
| Walda | MLC‐B | MLC‐Z | MinP‐J | PC80 | LC‐B | LC‐Z | SSB | SSBw | SKAT | SKAT‐O | MinP‐M | |
| Stat | 71.6 | 62.5 | 60.9 | 10.76 | 60.4 | 32.7 | 32.5 | 0.019 | 146.45 | – | – | 45.46 |
| df | 10 | 5 | 5 | – | 4 | 1 | 1 | – | – | – | – | – |
| P | 2.18 × 10−11 | 3.69 × 10−12 | 7.96 × 10−12 | 0.009 | 2.39 × 10−12 | 1.09 × 10−8 | 1.17 × 10−8 | 1.98 × 10−9 | 2.83 × 10−12 | 5.402 × 10−11 | 2.16 × 10−10 | 1.40 × 10−10 |
List of test statistics: Wald: generalized Wald test (10 df); MLC‐B: MLC test using beta coefficients; MLC‐Z: MLC test using Z statistics; LC‐B: linear combination test using beta coefficients; LC‐Z: linear combination test using Z statistics; MinP‐J: minimum P‐value test based on joint regression analysis; MinP‐M: minimum P‐value test based on marginal regression analysis; PC80: global test based on regression using the minimum number of principal components capturing 80% of variance (Gauderman et al., 2007); SSB: sum of squared marginal beta coefficients (Pan, 2009); SSBw: Sum of squared marginal beta coefficients with inverse variance weights (Pan, 2009); SKAT: SKAT for common variants with weights obtained from Beta(0.5,0.5) density function (Ionita‐Laza et al., 2013); SKAT‐O: Linear combination of SKAT and burden test with optimized mixing proportion (Lee et al., 2012).