TABLE 4.

Candidate gene analysis of hypothalamic–pituitary–adrenal axis gene methylation and cortisol levels

Gene	Genomic region (hg19)	# EPIC probes a	Correlated CpGs b	CpG	Location (hg19)	r	H.adj.p
Brain derived neurotrophic factor (BDNF)	Chr11: 27670031–27747452	87	4	cg02386994	chr11:27723290	−0.20	0.029*
				cg27193031	chr11:27721088	0.26	0.004**
				cg25328597	chr11:27722638	0.21	0.022*
				cg04672351	chr11:27722889	0.23	0.012*
Corticotropin releasing hormone (CRH)	Chr8: 67088055–67091520	13	1	cg21240762	chr8:67089388	−0.23	0.011*
Corticotropin releasing hormone receptor 1 (CRHR1)	Chr17: 43853226–43926706	53	4	cg15834779	chr17:43919576	−0.18	0.046*
				cg10106856	chr17:43880210	0.20	0.028*
				cg03323388	chr17:43888776	−0.20	0.027*
				cg15844800	chr17:43916233	0.23	0.012*
Corticotropin releasing hormone receptor 2 (CRHR2)	Chr7: 30682632–30750930	47	2	cg26262196	chr7: 30696540	0.19	0.035*
				cg09797340	chr7:30749389	−0.23	0.012*
FK506‐binding proteins (FKBP) prolyl isomerase 5 (FKBP5)	Chr6: 35501361–35700207	57	1	cg26868354	chr6:35699952	0.20	0.026*
Nuclear receptor subfamily 3 group C member 1 (NR3C1)	Chr5: 142640230–142851250	85	3	cg14939152	chr5:142783831	0.27	0.003**
				cg21209684	chr5:142783848	−0.22	0.018*
				cg17349736	chr5:142802329	−0.25	0.007**
Nuclear receptor subfamily 3 group C member 1 (NR3C2)	Chr4: 148912932–149414546	67	4	cg09143276	chr4:149066518	−0.22	0.016*
				cg07335874	chr4:149136507	0.21	0.023*
				cg06240648	chr4:149289762	−0.19	0.039*
				cg23329208	chr4:149360981	0.23	0.011*
Total	‐	407	19

Abbreviations: CpG, cytosine‐phosphate‐guanine; EPIC, Infinium MethylationEPIC array; H.adj.p, Holm multiple testing adjusted p‐value; hg19, Homo sapiens (human) genome assembly GRCh37; r, correlation coefficient.

* p < 0.05, ** p < 0.01.

^a total number of CpG probes in the gene region (after removal of cross reactive and failed probes).

^b probes with methylation significantly correlated with continuous cortisol levels after adjustment for multiple testing using the Holm method.