DNA methylation links prenatal smoking exposure to later life health outcomes in offspring

Wiklund, Petri; Karhunen, Ville; Richmond, Rebecca C.; Parmar, Priyanka; Rodriguez, Alina; De Silva, Maneka; Wielscher, Matthias; Rezwan, Faisal I.; Richardson, Tom G.; Veijola, Juha; Herzig, Karl-Heinz; Holloway, John W.; Relton, Caroline L.; Sebert, Sylvain; Järvelin, Marjo-Riitta

doi:10.1186/s13148-019-0683-4

Clinical Epigenetics

Table 2 Association results for the leading CpG sites from each locus selected for the sensitivity and downstream analyses

From: DNA methylation links prenatal smoking exposure to later life health outcomes in offspring

			Meta-analysis			Sensitivity and downstream analyses
			5 studies, N = 2821			Never-smokers, N = 1298			Paternal smoking, N = 1774			Dose-response analysis, N = 1134
CpG	Chr	Gene	β	SE	P value	β	SE	P value	β	SE	P value	β	SE	P value
cg15325070	1		0.014	0.003	9.23E−08	0.009	0.004	1.92E−02	0.000	0.003	9.16E−01	0.168	0.034	6.81E−07
cg25189904	1	GNG12	− 0.020	0.003	1.28E−10	− 0.018	0.004	1.87E−05	− 0.004	0.003	1.52E−01	− 0.146	0.032	5.85E−06
cg14179389	1	GFI1	− 0.028	0.003	5.00E−20	− 0.027	0.004	1.07E−09	− 0.004	0.003	1.77E−01	− 0.214	0.031	4.92E−12
cg04749740	2		0.015	0.003	9.21E−08	0.015	0.004	9.64E−04	0.004	0.003	1.03E−01	0.061	0.034	6.98E−02
cg06635952	2	ANXA4	0.011	0.002	5.54E−08	0.011	0.003	1.88E−04	0.001	0.002	9.53E−01	0.073	0.029	1.12E−02
cg11025974	2	CACNB4	0.016	0.002	9.06E−11	0.018	0.004	1.57E−07	− 0.001	0.002	6.41E−01	0.169	0.033	2.19E−07
cg14157435	2	NRP2	− 0.046	0.006	1.15E−13	− 0.042	0.008	6.01E−07	− 0.014	0.006	2.80E−02	− 0.201	0.033	9.33E−10
cg05783384	2		0.021	0.004	2.59E−08	0.014	0.005	1.15E−02	0.003	0.004	3.92E−01	0.097	0.033	3.26E−03
cg05204104	2	ARL4C	0.017	0.003	4.81E−12	0.016	0.004	6.02E−05	0.006	0.003	7.96E−02	0.036	0.033	2.73E−01
cg00174179	3	RHOA	− 0.006	0.001	7.01E−09	− 0.006	0.002	3.22E−04	− 0.002	0.001	5.21E−02	− 0.104	0.029	3.89E−04
cg16449012	4	FAM184B	0.014	0.002	3.10E−08	0.021	0.004	4.42E−08	0.003	0.002	1.62E−01	0.119	0.03	7.81E−05
cg05575921	5	AHRR	− 0.019	0.002	3.53E−18	− 0.011	0.003	1.19E−04	− 0.008	0.003	2.75E−03	− 0.134	0.027	5.91E−07
cg21253335	5		0.017	0.003	1.25E−08	0.014	0.004	1.12E−03	0.004	0.003	1.17E−01	0.108	0.033	1.04E−03
cg01952185	5		0.019	0.003	3.31E−12	0.017	0.004	5.81E−05	0.005	0.003	4.49E−02	0.128	0.03	1.67E−05
cg05634495	6		0.016	0.003	3.14E−08	0.014	0.005	2.54E−03	0.002	0.003	5.00E−01	0.088	0.033	6.86E−03
cg00794911	6		− 0.012	0.002	5.20E−10	− 0.007	0.003	1.25E−02	− 0.005	0.002	1.15E−02	− 0.115	0.034	6.42E−04
cg25879142	7		0.018	0.003	1.79E−08	0.013	0.004	3.05E−03	0.003	0.003	3.73E−01	0.121	0.031	1.23E−04
cg20117519	7		0.022	0.004	2.39E−08	0.022	0.006	1.70E−04	0.007	0.004	4.08E−02	0.112	0.033	6.72E−04
cg19089201	7	MYO1G	0.035	0.003	1.18E−31	0.030	0.004	5.75E−12	0.007	0.003	1.51E−02	0.225	0.032	2.24E−12
cg04598670	7		− 0.019	0.003	8.33E−08	− 0.016	0.005	4.54E−03	− 0.007	0.003	3.95E−02	− 0.178	0.034	1.54E−07
cg25949550	7	CNTNAP2	− 0.007	0.001	5.41E−27	− 0.007	0.001	1.45E−14	− 0.002	0.001	6.57E−03	− 0.157	0.022	1.65E−12
cg11207515	7	CNTNAP2	− 0.023	0.003	1.03E−13	− 0.020	0.004	2.75E−06	− 0.011	0.003	2.46E−04	− 0.145	0.032	7.02E−06
cg15578140	7	MIR548F3	0.011	0.002	7.54E−09	0.014	0.003	7.89E−06	− 0.001	0.002	5.70E−01	0.152	0.031	1.12E−06
cg17199018	8	ZNF395	− 0.017	0.003	3.85E−09	− 0.016	0.004	7.10E−05	− 0.003	0.003	3.10E−01	− 0.121	0.033	2.63E−04
cg14563637	9		0.016	0.003	1.19E−09	0.016	0.004	9.26E−05	0.003	0.002	1.69E−01	0.092	0.031	3.26E−03
cg14540913	9	PRRX2	0.013	0.002	7.57E−09	0.015	0.003	1.81E−05	0.001	0.002	5.79E−01	0.148	0.032	2.62E−06
cg13822849	9	OLFM1	0.007	0.001	2.87E−08	0.007	0.002	5.84E−05	0.003	0.002	2.90E−02	0.126	0.03	3.24E−05
cg11813497	10	FRMD4A	0.026	0.003	9.27E−19	0.022	0.004	1.46E−07	− 0.001	0.003	6.26E−01	0.117	0.032	2.81E−04
cg05697249	11	C11orf52	0.015	0.002	1.30E−11	0.015	0.003	8.68E−06	0.003	0.002	1.54E−01	0.136	0.035	8.25E−05
cg18493761	11		0.037	0.004	7.30E−21	0.032	0.006	4.99E−08	0.008	0.004	2.60E−02	0.154	0.034	4.82E−06
cg05549655	15	CYP1A1	0.010	0.001	1.04E−28	0.009	0.001	6.03E−13	0.002	0.001	4.28E−02	0.230	0.028	1.92E−16
cg13834112	15		0.013	0.002	3.55E−08	0.018	0.004	6.39E−07	0.001	0.002	8.10E−01	0.120	0.031	1.24E−04
cg00253658	16		0.037	0.004	3.44E−19	0.032	0.006	6.54E−08	0.005	0.005	2.81E−01	0.166	0.033	4.83E−07
cg04358214	16	C16orf70	0.022	0.004	9.56E−08	0.021	0.006	5.93E−04	0.005	0.004	2.42E−01	0.090	0.031	3.94E−03
cg12984635	19	ETHE1	0.015	0.002	2.17E−09	0.014	0.003	5.87E−05	0.001	0.002	7.33E−01	0.116	0.031	1.49E−04
cg06758350	21	RUNX1	0.030	0.005	1.68E−10	0.016	0.007	2.03E−02	0.002	0.005	7.09E−01	0.140	0.034	3.92E−05

The analyses were conducted separately in each participating cohort, adjusted for study-specific covariates as necessary, and combined using inverse-variance weighted fixed-effects meta-analysis. The effect size estimates for the dose-response analysis represent the difference in blood DNA methylation (in standard deviation units) per three additional cigarettes smoked per day in pregnancy
Chr chromosome, β effect size estimate, SE standard error

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ISSN: 1868-7083

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