Table 3.
Step 1 Mendelian Randomization Results for the Association Between Ever Smoking Status and the DNA Methylation Levels of cg03636183 in the F2RL3 Gene and cg19859270 in the GPR15 Gene, GENOA Study, Jackson, Mississippi, 2000–2005
| Gene and Instrument SNPa |
Cytosine-Phosphate-Guanine Site | |||||
|---|---|---|---|---|---|---|
| cg03636183 in F2RL3 | cg19859270 in GPR15 | |||||
| βb | 95% CI | P Value | βb | 95% CI | P Value | |
| CHRNB4 | ||||||
| rs9920506 | −0.62 | −0.82, −0.41 | 9.1 × 10−9 | −0.22 | −0.29, −0.16 | 3.1 × 10−11 |
| rs8023822 | −0.57 | −0.76, −0.38 | 1.1 × 10−8 | −0.20 | −0.26, −0.14 | 4.3 × 10−10 |
| LOC105370913 | ||||||
| rs4887077 | −0.54 | −0.73, −0.34 | 1.8 × 10−7 | −0.20 | −0.26, −0.14 | 6.8 × 10−10 |
| rs11638372 | −0.55 | −0.75, −0.35 | 9.0 × 10−8 | −0.20 | −0.26, −0.14 | 4.2 × 10−10 |
| rs922692 | −0.57 | −0.77, −0.37 | 4.8 × 10−8 | −0.20 | −0.27, −0.14 | 3.7 × 10−10 |
| rs11072791 | −0.57 | −0.77, −0.37 | 2.8 × 10−8 | −0.21 | −0.27, −0.15 | 5.3 × 10−11 |
| ADAMTS7 | ||||||
| rs12286 | −0.47 | −0.65, −0.29 | 5.0 × 10−7 | −0.19 | −0.25, −0.14 | 1.7 × 10−10 |
| rs1809420 | −0.41 | −0.59, −0.24 | 3.8 × 10−6 | −0.18 | −0.23, −0.12 | 1.2 × 10−9 |
| rs7174367 | −0.45 | −0.63, −0.28 | 5.9 × 10−7 | −0.18 | −0.24, −0.13 | 5.0 × 10−10 |
| rs3825807 | —c | — | — | −0.21 | −0.27, −0.15 | 7.8 × 10−11 |
| rs7177699 | — | — | — | −0.21 | −0.27, −0.15 | 1.1 × 10−10 |
| GRSd | −0.41 | −0.59, −0.24 | 3.0 × 10−6 | −0.17 | −0.22, −0.11 | 5.6 × 10−9 |
Abbreviations: ADAM, a disintegrin and metalloproteinase; ADAMTS7, ADAM metallopeptidase with thrombospondin type 1 motif 7; CHRNB4, cholinergic receptor, nicotinic β 4; CI, confidence interval; F2RL3, coagulation factor II (thrombin) receptor-like 3; GENOA, Genetic Epidemiology Network of Arteriopathy; GPR15, G protein-coupled receptor 15; GRS, genetic risk score; LOC105370913, uncharacterized LOC105370913; SNP, single nucleotide polymorphism.
a The instrument SNPs were identified in previous genome-wide association studies of cigarette smoking in an independent cohort and satisfied the assumptions of Mendelian randomization in GENOA.
b β coefficient for the exposure (ever smoking status) in the second stage of 2-stage least-squares regression analysis. In all models, results were adjusted for age, sex, plate, 4 principal components, 5 cell proportions, and random intercepts for family.
c Missing data for the Mendelian randomization results because of the violation of assumption 2.
d GRS = [rs9920506 + rs4887077 + rs12286]/3. When the coded allele was negatively associated with ever smoking status, we coded for the other allele by subtracting the allele dosage from 2.