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 3 Results from meta-analysis, FEV_1/FVC 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	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	0.10	0.14	−++	−0.02	0.79	+ − +	−0.01	0.79	– − +	0.00	0.82	+ − –
cg25042671	94,849,061	Body	−0.59	0.04	−0.09	0.29	− + −	− 0.12	0.22	– – –	−0.12	0.03	+ − –	0.00	0.62	+ − +
cg20267408	94,849,703	5UTR	−0.44	0.21	−0.05	0.57	– – –	0.05	0.59	−++	0.01	0.88	+ − +	0.00	0.78	−++
cg26938334	94,849,747	5UTR	1.16	0.42	0.10	0.24	− + −	−0.10	0.47	−++	0.01	0.84	++−	−0.01	0.33	– − +
cg10832639	94,850,965	5UTR	−0.25	0.72	0.16	0.14	+ − +	0.02	0.86	− + −	0.08	0.18	+++	0.01	0.32	+++
cg02126235	94,855,034	5UTR	−0.30	0.58	0.26	0.06	+++	0.06	0.71	− + −	0.06	0.41	++−	0.00	0.90	– − +
cg09968361	94,855,344	5UTR	−0.33	0.44	0.11	0.23	+++	0.00	0.99	++−	0.05	0.25	++−	−0.01	0.37	– − +
cg13826459	94,855,505	TSS1500	−0.08	0.76	0.07	0.34	+ − +	0.15	0.05	+ − +	0.04	0.32	+++	0.01	0.24	−++
cg25968219	94,855,590	TSS1500	−1.81	0.05	0.31	0.02	+++	−0.16	0.43	– − +	− 0.01	0.90	−++	0.00	0.59	+ − +
cg01606800	94,855,990	TSS1500	−1.08	0.001	0.17	0.05	+ − +	0.01	0.96	– − +	0.00	0.97	– − +	0.00	0.73	++−
cg02181506	94,856,984	1stExon	−0.78	0.08	−0.01	0.89	+ − –	0.05	0.64	+ − –	−0.03	0.58	+ − –	0.00	0.80	++−
cg10070185	94,857,151	TSS200	−0.05	0.91	0.07	0.45	+++	0.19	0.09	−++	−0.01	0.81	– − +	0.00	0.63	– − +
cg24621042	94,857,275	TSS1500	−0.68	0.04	0.18	0.02	+++	0.16	0.08	+++	0.07	0.09	+++	−0.01	0.09	+ − –
cg00802237	94,858,066	TSS1500	−0.07	0.81	0.03	0.71	+ − +	−0.14	0.09	– – –	0.00	0.96	−++	0.00	0.50	+ − –
cg04179148	94,858,339	TSS1500	−0.70	0.06	0.20	0.03	+++	0.04	0.73	++−	0.12	0.02	+++	0.00	0.57	– – –

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
Results from Meta-Analysis of Lung Function Association of Methylation of CpGs in the SERPINA1* Gene with FEV1/FVC 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 × x10^-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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