Table 2.

Step 1 Mendelian Randomization Results for the Association Between Current 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
BDNF-AS
rs4074134	−0.64	−0.84, −0.45	3.9 × 10−10	−0.21	−0.27, −0.15	1.7 × 10−10
rs4923457	−0.64	−0.84, −0.45	4.0 × 10−10	−0.21	−0.27, −0.15	1.7 × 10−10
rs4923460	−0.65	−0.85, −0.45	4.7 × 10−10	−0.21	−0.27, −0.15	3.0 × 10−10
IREB2
rs1964678	−0.47	−0.65, −0.29	6.5 × 10−7	−0.20	−0.26, −0.14	9.4 × 10−11
HYKK
rs952216	−0.47	−0.65, −0.29	6.2 × 10−7	−0.20	−0.26, −0.15	1.7 × 10−11
rs11636131	−0.48	−0.67, −0.29	7.9 × 10−7	−0.21	−0.27, −0.15	1.4 × 10−11
rs11632604	−0.48	−0.67, −0.29	8.1 × 10−7	−0.21	−0.27, −0.15	1.4 × 10−11
rs12910289	−0.49	−0.68, −0.30	6.6 × 10−7	−0.22	−0.28, −0.16	1.1 × 10−11
rs1504546	−0.48	−0.67, −0.29	8.8 × 10−7	−0.21	−0.27, −0.15	1.5 × 10−11
rs12916999	−0.48	−0.67, −0.29	9.1 × 10−7	−0.21	−0.27, −0.15	1.5 × 10−11
PSMA4
rs12915366	−0.48	−0.66, −0.29	9.6 × 10−7	−0.21	−0.27, −0.15	1.5 × 10−11
rs12916483	−0.48	−0.66, −0.29	9.7 × 10−7	−0.21	−0.27, −0.15	1.5 × 10−11
rs3813571	−0.46	−0.64, −0.27	1.8 × 10−6	−0.21	−0.27, −0.15	2.2 × 10−11
CHRNA3
rs1317286	—c	—	—	−0.18	−0.25, −0.11	5.2 × 10−7
GRSd	−0.18	−0.30, −0.07	2.4 × 10−3	−0.11	−0.15, −0.07	1.5 × 10−7

Abbreviations: BDNF-AS, brain-derived neurotrophic factor antisense RNA; CHRNA3, cholinergic receptor, nicotinic α 3; 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; HYKK, hydroxylysine kinase; IREB2, iron-responsive element binding protein 2; PSMA4, proteasome subunit α 4; 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 (current 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 = [rs4074134 + (2 − rs1964678) + (2 − rs952216) + (2 − rs12915366) + (2 − rs1317286)]/5. When the coded allele was negatively associated with current smoking status, we coded for the other allele by subtracting the allele dosage from 2.