Table 1.

Results of pathway and functional analysis in ARIC discovery meta-analysis and TFAM knockout methylation and expression datasets with combined P value and ARIC P value < 0.05. TFAM integrated (INT) P value represents combined methylation and expression results. Combined P value represents combined ARIC and TFAM methylation and expression results

		ARIC P value	TFAM METH P value	TFAM RNA P value	TFAM INT P value	Combined pathway P value (ARIC, TFAM-METH, TFAM-RNA)
A. KEGG pathways sorted by combined P value
Pathway	Name
path:hsa04080	Neuroactive ligand receptor interaction	5.24E−12	4.41E−04	4.30E−04	8.77E−06	8.96E−16
path:hsa05033	Nicotine addiction	8.99E−04	6.30E−05	9.32E−04	7.72E−06	1.61E−08
path:hsa04024	cAMP signaling pathway	1.29E−05	2.32E−02	2.23E−01	3.25E−01	1.03E−05
path:hsa04614	Renin-angiotensin system	1.04E−05	5.11E−02	1.00E+ 00	1.00E+ 00	6.37E−05
path:hsa04723	Retrograde endocannabinoid signaling	1.89E−04	1.84E−02	1.56E−01	3.66E−03	6.48E−05
path:hsa05032	Morphine addiction	1.26E−02	4.38E−02	5.15E−02	1.40E−03	1.88E−03
path:hsa05031	Amphetamine addiction	3.54E−02	9.64E−02	4.23E−01	1.19E−01	4.18E−02
path:hsa04724	Glutamatergic synapse	1.80E−02	9.49E−02	1.00E+ 00	1.00E+ 00	4.73E−02
B. GO pathways sorted by combined P value
Function	Name
GO:0007267	Cell-cell signaling	1.42E−03	1.71E−05	1.19E−02	1.42E−02	7.63E−08
GO:0099537	Trans-synaptic signaling	1.88E−03	1.06E−05	6.27E−02	1.92E−02	2.89E−07
GO:0099536	Synaptic signaling	1.88E−03	1.08E−05	6.34E−02	1.92E−02	2.97E−07
GO:0007268	Chemical synaptic transmission	1.88E−03	2.22E−05	6.05E−02	1.87E−02	5.47E−07
GO:0098916	Anterograde trans-synaptic signaling	1.88E−03	2.22E−05	6.05E−02	1.87E−02	5.47E−07
GO:0099095	Ligand-gated anion channel activity	4.30E−02	8.02E−04	1.23E−04	3.74E−07	8.74E−07
GO:0045202	Synapse	1.98E−04	9.81E−05	2.74E−01	5.92E−03	1.07E−06
GO:0045211	Postsynaptic membrane	8.33E−03	1.03E−04	1.45E−01	6.19E−04	1.78E−05