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)

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

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