Abnormal DNA methylation within genes of the steroidogenesis pathway two years after paediatric critical illness and association with stunted growth in height further in time

Table 3 Association with stunted growth in height of long-term abnormal DNA methylation within steroidogenic genes in former PICU patients

Gene	CpG site	Gene section ^a,b	Percentage of significant iterations ^c	Median (IQR) P-value ^d	Direction of association ^e
CYP11A1	cg23808031	Promoter/ 1stExon	100	2.8E-26 (1.8E-26–3.7E-26)	Harm
POR	cg10738873	5'UTR	100	2.2E-11 (1.7E-11–2.9E-11)	Harm
	cg17115737	5'UTR	100	6.3E-13 (5.0E-13–8.1E-13)	Harm
	cg27372063	Body	100	1.2E-24 (8.4E-25–1.5E-24)	Harm
CYB5A	cg18274065	Promoter	100	4.6E-29 (3.5E-29–6.4E-29)	Harm
HSD17B1	cg02363277	Body	100	1.7E-10 (1.4E-10–2.0E-10)	Harm
HSD17B2	cg09894383	Promoter	100	8.6E-40 (5.2E-40–1.2E-39)	Harm
	cg11515282	Promoter	100	8.3E-87 (4.7E-87–1.2E-86)	Harm
	cg20373326	Promoter	100	1.9E-75 (1.2E-75–3.0E-75)	Harm
	cg19807685	5'UTR/ 1stExon	100	1.5E-37 (1.0E-37–2.0E-37)	Harm
	cg26315602	1stExon	100	8.1E-28 (5.6E-28–1.3E-27)	Harm
	cg00365986	Body	100	6.4E-32 (4.3E-32–9.6E-32)	Harm
	cg05315365	Body	100	2.6E-80 (1.6E-80–5.0E-80)	Harm
	cg13740036	Body	100	2.5E-80 (1.6E-80–4.5E-80)	Harm
HSD17B3	cg18014207	Body	100	1.3E-25 (9.3E-26–1.7E-25)	Harm
HSD17B6	cg21922731	5'UTR/ 1stExon	100	8.7E-07 (6.6E-07–1.0E-06)	Harm
HSD17B10	cg26323797	Promoter	100	0.014 (0.013–0.016)	Harm
HSD17B12	cg14262884	Body	100	3.0E-20 (2.1E-20–4.2E-20)	Harm
	cg21077321	Body	100	7.3E-27 (5.6E-27–1.0E-26)	Harm
CYP19A1	cg12009872	Body	100	4.5E-14 (3.3E-14–6.1E-14)	Harm
	cg14424631	Body	100	8.9E-07 (7.2E-07–1.0E-06)	Harm
CYP21A2	cg11675917	Promoter	100	5.9E-09 (4.9E-09–6.8E-09)	Harm
CYP11B2	cg14389499	Promoter	100	4.7E-10 (3.8E-10–6.0E-10)	Harm

This table summarises the results of the multivariable linear regression analyses assessing associations between abnormal DNA methylation within genes involved in steroidogenesis 2 years after critical illness and height at 4-year follow-up, adjusted for baseline risk factors and technical variation
UTR untranslated region
^aA CpG site can be located within multiple 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
^cPercentage of the 100 iterations for which the Fisher P-values across the 10 test folds is significant (P < 0.05)
^dMedian and interquartile range of the Fisher P-values across the 10 test folds obtained for the 100 iterations
^eThe label “Harm” for robust associations (significant in at least 50% of the iterations) indicates that the observed abnormal DNA methylation correlates with a shorter height (based on the mean coefficient from the multivariable models)

ISSN: 1868-7083