SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts

Beckmeyer-Borowko, Anna; Imboden, Medea; Rezwan, Faisal I.; Wielscher, Matthias; Amaral, Andre F. S.; Jeong, Ayoung; Schaffner, Emmanuel; Auvinen, Juha; Sebert, Sylvain; Karhunen, Ville; Bettschart, Robert; Turk, Alexander; Pons, Marco; Stolz, Daiana; Kronenberg, Florian; Arathimos, Ryan; Sharp, Gemma C.; Relton, Caroline; Henderson, Alexander J.; Jarvelin, Marjo-Riitta; Jarvis, Deborah; Holloway, John W.; Probst-Hensch, Nicole M.

doi:10.1186/s12931-018-0850-8

Table 2 Results from Meta-Analyses, FEV₁ and AAT, Adult Cohorts

From: SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts

CpG	CpG Position	Gene Group	SAPALDIA		Meta- Analysis of Lung Function Association in SAPALDIA, NFBC and ECRHS
			Circulating AAT		Cross-Sectional T1			Cross-Sectional T2			Repeat Cross-Sectional			Change
			Coef.	P.value^a	Coef.	P.value^a	Direction^b	Coef.	P.value^a	Direction^b	Coef.	P.value^a	Direction^b	Coef.	P.value^a	Direction^b
cg10761141	94,844,776	3UTR	−0.30	0.25	0.75	0.13	+++	0.63	0.21	+ − +	−0.04	0.84	+ − –	0.02	0.48	+++
cg25042671	94,849,061	Body	−0.59	0.04	−0.72	0.25	− + −	− 0.80	0.21	– − −	−0.22	0.52	++−	−0.03	0.44	− + −
cg20267408	94,849,703	5UTR	−0.44	0.21	−0.15	0.82	++−	−0.05	0.94	++−	0.10	0.79	++−	0.00	0.97	+ − –
cg26938334	94,849,747	5UTR	1.16	0.42	− 0.01	0.99	− + −	− 0.35	0.74	− + −	− 0.33	0.34	– − +	− 0.01	0.71	– – –
cg16110645	94,850,433	5UTR	− 0.64	0.34	0.39	0.67	−++	0.55	0.59	+ − +	0.08	0.85	+ − +	−0.02	0.75	– − +
cg10832639	94,850,965	5UTR	−0.25	0.72	1.24	0.16	+++	0.01	0.99	−++	0.18	0.61	−++	0.00	0.95	++−
cg02126235	94,855,034	5UTR	−0.30	0.58	0.76	0.45	+++	0.67	0.55	++−	− 0.26	0.55	– – –	0.02	0.69	++−
cg22828990	94,855,099	5UTR	−0.09	0.82	0.19	0.79	– − +	0.30	0.68	– − +	0.69	0.03	+ − +	−0.09	0.04	– – –
cg09968361	94,855,344	5UTR	−0.33	0.44	1.43	0.04	+++	0.65	0.36	−++	0.72	0.02	+++	−0.10	0.01	–
cg13826459	94,855,505	TSS1500	−0.08	0.76	0.16	0.76	−++	0.98	0.05	+++	−0.05	0.83	− + −	0.04	0.15	+++
cg25968219	94,855,590	TSS1500	−1.81	0.05	3.29	0.003	+++	−1.29	0.37	– − +	0.37	0.59	++−	− 0.08	0.15	– − +
cg01606800	94,855,990	TSS1500	−1.08	0.001	0.47	0.47	−++	−0.13	0.85	– − +	− 0.11	0.73	– − +	− 0.01	0.75	– − +
cg02181506	94,856,984	1stExon	−0.78	0.08	0.11	0.89	– − +	0.65	0.40	+ − +	0.28	0.47	+ − +	0.02	0.71	+ − –
cg10070185	94,857,151	TSS200	−0.05	0.91	0.37	0.59	– − +	1.08	0.16	+++	0.24	0.39	−++	0.04	0.29	+ − +
cg24621042	94,857,275	TSS1500	−0.68	0.04	0.87	0.14	+++	1.16	0.06	+++	−0.15	0.60	− + −	− 0.01	0.87	+ − +
cg00802237	94,858,066	TSS1500	−0.07	0.81	−0.01	0.99	+ − –	− 0.48	0.40	– − +	0.12	0.67	+ − +	−0.03	0.35	– − +
cg04179148	94,858,339	TSS1500	−0.70	0.06	1.80	0.01	+++	0.29	0.67	+++	0.36	0.25	+++	−0.03	0.47	– – –

Cross-sectional and repeat cross-sectional models adjusted for: study center, age, age2, education, height, height2, sex, sex*age, (sex*age) 2, sex*height, (sex*height)2, Bcell, CD4T, CD8T, Eos, Mono, NK. Repeat cross-sectional in addition ran with a random intercept on the subject. In predictive models, annual change in lung function was computed as the difference between T2 and T1 divided by time of follow-up: (T2-T1)/follow-up models adjusted for covariates from T1
Sample size for circulating AAT for SAPALDIA n = 561. Cross-sectional and prediction models (change) n = 1076, and n = 1122 for repeat cross-sectional models
Meta-Analysis of Lung Function Association of Methylation of CpGs in the SERPINA1* Gene with FEV1 Level and Decline in Adult Ever-Smokers from SAPALDIA, ECRHS and NFBC and with Circulating AAT Concentrations in SAPALDIA
From SERPINA gene cluster located on chromosome 14 between positions: 94′641’781 and 95′235’125 (human genome build 37/hg19)
^aNominal P-values, Bonferroni corrected significance level for 119 tests is P-value 4.6 × 10^− 4
^bDirection of effect for SAPALDIA, ECRHS and NFBC. A positive sign indicates that an increase in methylation is associated with higher level of lung function (cross-sectional models) and with an attenuation of lung function decline, respectively (change model)
Statistically significant results are highlighted in bold

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ISSN: 1465-993X

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