Table 3.
Replicated loci from primary analyses of vitamin K pathway-related variants
| Gene | SNP | HWEa | Cohort | Modelb | Effect Size (±SE) | P-valuec |
|---|---|---|---|---|---|---|
| ACSM6, Uncharacterized LOC107984257 | chr10:95205120:G:A (rs650243)d | 1.00 | Tucson | PC | 11.03 (±3.799) | 4.29×10−3 |
| 0.22 | San Juan | PC | 9.737 (±3.634) | 8.74×10−3 | ||
| Tucson | IWPC | 4.74 (±2.7) | 0.08 | |||
| San Juan | IWPC | 7.37 (±3.51) | 0.04 | |||
| COX10 | chr17:14207584:A:C (rs11078234) | 1.80×10−3 | Tucson | PC | 6.454 (±2.21) | 4.10×10−3 |
| 0.42 | San Juan | PC | 5.706 (±2.009) | 5.56×10−3 | ||
| Tucson | IWPC | 4.1 (±1.54) | 8.95×10−3 | |||
| San Juan | IWPC | 4.08 (±2.27) | 0.08 | |||
| VKORC1 | chr16:31093188:C:A (rs8050894) | 0.87 | Tucson | PC | −8.745 (±1.743) | 1.6×10−6 |
| 0.51 | San Juan | PC | −4.92 (±1.633) | 3.36×10−3 | ||
| Tucson | IWPC | −7.42 (±5.29) | 0.16 | |||
| San Juan | IWPC | −6.09 (±1.94) | 2.30×10−3 | |||
| VKORC1 | chr16:31093557:G:A (rs9934438) | 0.61 | Tucson | PC | −9.011 (±1.804) | 1.78×10−6 |
| 0.10 | San Juan | PC | −4.727 (±1.605) | 4.10×10−3 | ||
| Tucson | IWPC | - | - | |||
| San Juan | IWPC | - | - |
--hardy in plink1.9 tells the null hypothesis that observed genotype frequencies are not significantly different from those predicted for a population in equilibrium
Model refers to the regression that produced the outlined result, where PC stands for adjustment for the top three principal components, and IWPC stands for adjustment for the variables included in the IWPC dose prediction algorithm38 IWPC models were adjusted for age, height, weight, genotypes at VKORC1 and CYP2C9, amiodarone use and enzyme inducer use.
Hypotheses were tested with --linear of PLINK1.9, and with lm() from the stats package in R in IWPC adjusted models, a p-value less than 0.0125 is summarized as p < 0.0125
chr10:95197958:T:A (rs619297), in complete linkage, was also replicated
SNP indicates single nucleotide polymorphism; HWE, Hardy Weinberg Equilibrium; SE, standard error; ACSM6, Acyl-CoA Synthetase Medium Chain Family Member 6; COX10, Cytochrome C Oxidase Assembly Factor Heme A:Farnesyltransferase; VKORC1, Vitamin K epoxide reductase complex subunit 1; PC, principal components; and IWPC, international warfarin pharmacogenetics consortium