Abnormal DNA methylation within HPA-axis genes years after paediatric critical illness

Coppens, Grégoire; Vanhorebeek, Ilse; Güiza, Fabian; Derese, Inge; Wouters, Pieter J.; Téblick, Arno; Dulfer, Karolijn; Joosten, Koen F.; Verbruggen, Sascha C.; Van den Berghe, Greet

doi:10.1186/s13148-024-01640-y

Clinical Epigenetics

Table 2 Abnormal DNA methylation within the HPA-axis

From: Abnormal DNA methylation within HPA-axis genes years after paediatric critical illness

Gene	CpG site	Gene section^a,b	Former PICU patients versus healthy children						Former PICU patients: GC versus No CG treatment
			Methylation status^c	Log Fold Change [Confidence Interval]^d	Absolute mean difference^e	p value^f			p value^f
			Methylation status^c	Log Fold Change [Confidence Interval]^d	Absolute mean difference^e	Pt vs Ctrl^g	Int. sex	Int. age	p value^f
CRHR1	cg15607306	Body	Hypo	− 0.066 [− 0.108 to − 0.023]	0.004	0.049	0.87	0.91	0.77
POMC	cg09672383	5’UTR	Hypo	− 0.082 [− 0.135 to − 0.03]	0.018	0.049	0.70	0.62	0.11
MC2R	cg26344168	Body	Hypo	− 0.07 [− 0.113 to − 0.027]	0.011	0.049	0.44	0.52	0.83
NR3C1	cg26720913	5’UTR/1stExon	Hypo	− 0.163 [− 0.265 to − 0.062]	0.037	0.049	0.46	0.27	0.14
	cg01967637	Promoter/5’UTR/1stExon	Hyper	0.1 [0.037 – 0.163]	0.02	0.049	0.33	0.84	0.080
	cg15910486	Promoter/5’UTR	Hyper	0.09 [0.039 – 0.141]	0.02	0.033	0.64	0.87	0.62
FKBP5	cg23416081	5’UTR	Hypo	− 0.292 [− 0.432 to − 0.152]	0.055	0.0052	0.54	0.48	0.017
	cg15929276	5’UTR	Hypo	− 0.252 [− 0.397 to − 0.107]	0.051	0.037	0.36	0.83	0.0045
	cg03591753	5’UTR	Hypo	− 0.132 [− 0.176 to − 0.088]	0.031	< 0.00001	0.58	0.0060	0.26
	cg20813374	Promoter/5’UTR	Hypo	− 0.126 [− 0.183 to − 0.07]	0.02	0.0019	0.91	0.055	0.60
	cg03546163	5’UTR	Hypo	− 0.178 [− 0.248 to − 0.108]	0.029	0.00012	0.97	0.00063	0.92
	cg01839003	5’UTR	Hypo	− 0.077 [− 0.125 to − 0.029]	0.007	0.049	0.37	0.11	0.036
	cg22363520	Body	Hypo	− 0.253 [− 0.338 to − 0.167]	0.017	< 0.00001	0.83	0.10	0.068
HSD11B1	cg06571187	Promoter/5’UTR	Hypo	− 0.108 [− 0.177 to − 0.039]	0.017	0.049	0.94	0.027	0.18
HSD11B1	cg14139038	Promoter/5’UTR	Hypo	− 0.078 [− 0.118 to − 0.039]	0.01	0.0098	0.42	0.0020	0.49
SRD5A1	cg22911074	Promoter	Hyper	0.081 [0.031 – 0.13]	0.01	0.049	0.72	0.90	0.018
AKR1D1	cg02118020	Body	Hyper	0.188 [0.067 – 0.31]	0.047	0.049	0.25	0.25	0.017
	cg05082563	Body	Hypo	− 0.127 [− 0.208 to − 0.046]	0.024	0.049	0.81	0.67	0.11
	cg27250318	Body	Hypo	− 0.181 [− 0.29 to − 0.071]	0.033	0.049	0.70	0.42	0.16
	cg09373725	Body	Hypo	− 0.098 [− 0.159 to − 0.038]	0.015	0.049	0.82	0.22	0.45
DUSP1	cg00593243	Body	Hyper	0.184 [0.071 – 0.297]	0.042	0.049	0.28	0.34	0.11
TSC22D3	cg26954928	Body	Hypo	− 0.099 [− 0.161 to − 0.037]	0.002	0.049	0.38	0.061	0.41
TSC22D3	cg11907074	Promoter/Body	Hyper	0.114 [0.052 – 0.176]	0.008	0.020	0.86	0.56	0.69
TNF	cg10650821	1stExon	Hypo	− 0.059 [− 0.09 to − 0.029]	0.014	0.012	0.82	0.45	0.17
	cg26729380	1stExon	Hypo	− 0.052 [− 0.085 to − 0.019]	0.01	0.049	0.75	0.80	0.66
	cg08553327	1stExon	Hypo	− 0.062 [− 0.099 to − 0.025]	0.01	0.049	0.89	0.49	0.28

GC glucocorticoid, PICU paediatric intensive care unit, UTR untranslated region, Pt vs Ctrl former PICU vs healthy control children, Int. interaction with
^aA CpG site can be located within multiple genes or splice variants and thus can be situated within multiple gene sections
^bPromoter is defined as 0 to 1500 base pairs upstream of the transcription start site
^cThe methylation status of the former PICU patients compared to Healthy control children. ‘Hypo’ refers to the former PICU patients showing less methylation in a given CpG site (hypomethylated) compared to the healthy controls. ‘Hyper’ refers to the former PICU patients showing more methylation in a given CpG site (hypermethylated)
^dLog FC: Log fold change in M values between former PICU patients and healthy controls adjusted for risk factors. The 95% confidence interval is shown
^e The absolute mean difference is the (unadjusted) absolute difference between the mean beta value of a given CpG within the Former PICU patients and the mean beta value of a given CpG within the healthy control children
^f p values extracted from multivariable linear regression models, adjusted for baseline risk factors and technical variation. All p values come from separate models
^g Adjusted for multiple testing using a false discovery rate smaller than or equal to 0.05

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