Table 1.
Top feedforward (FF) ANS expressed genes affecting electrocardiogram (ECG) activity
| Gene identifier | Mouse ECG phenotype | Mouse behavioral phenotype | Human neuropsychiatric disease (NPD) association from GWAS catalog 2019 and MGI enriched terms |
|---|---|---|---|
| Psmc6 | HR ↑ HRV↓ | Hyperactivity, decreased thigmotaxis | Limited or no NPD annotations |
| 1700086L19Rik | rMSSD, HRV↓ | Hyperactivity | Limited or no NPD annotations |
| Mpst | PQ ↓,HR ↑,PR ↓ | Decreased exploration of a novel environment, increased latency to center entry, hypoactivity | Limited or no NPD annotations |
| Mdp1 | HR ↑ | Increased latency to the first transition into the dark in light/dark box, decreased % prepulse inhibition | Bipolar disorder, mood disorder |
| Gsg1l | HR ↓ (F),HR ↑ (M),RR ↑ (F),RR ↓ (M) | Hyperactivity, decreased startle response | Limited or no NPD annotations |
| Cdc26 | HR ↑ | Increased prepulse inhibition | Limited or no NPD annotations |
| Chmp2b | HR, RR ↑ | Abnormal freezing behavior in fear conditioning | Tourette's syndrome or obsessive–compulsive disorder, frontotemporal dementia |
| Pitx3 | HR ↑,ST, RR, QTc ↓ | Hyperactivity, Increased coping response, decreased vertical activity, decreased exploration of a novel environment | Cognitive ability, Parkinson’s disease |
| Prokr1 | HR ↑,RR ↓, rMSSD ↑ | No | Limited or no NPD annotations |
| Arid4b | HR,QRS ↑ | Decreased centre time | Limited or no NPD annotations |
| Zfp395 | HR ↑ST,RR ↓ | Hyperactivity | Limited or no NPD annotations |
| Stx1a | PQ↑,HR↓,ST,rMSSD,RR ↑HR_TTE ↓ | No | Disease of mental health |
| Hipk3 | HR ↓,RR, HRV ↑ | Decreased startle, hypoactivity, decreased prepulse inhibition, increased acoustic brainstem response thresholds | Limited or no NPD annotations |
| Srsf11 | HRV ↑ | Decreased prepulse inhibition | Limited or no NPD annotations |
| Tnnc1 | HRV ↑ | No | Feeling worry, Bipolar disorder, Autism spectrum disorder or schizophrenia |
| Kbtbd7 | HR ↓,RR ↑ | Hyperactivity, decreased thigmotaxis | Limited or no NPD annotations |
| Rasgef1a | HR ↓, RR↑ | Increased vertical activity | Recurrent major depressive disorder |
| Cap2 | HR↓,ST, rMSSD, RR, QTc ↑ | No | Limited or no NPD annotations |
| Bclaf1 | rMSSD ↑ | Hyperactivity | Limited or no NPD annotations |
| Entpd1 | rMSSD ↑ | No | Limited or no NPD annotations |
| 4931406C07Rik | HR ↓ rMSSD, HRV ↑ | No | Limited or no NPD annotations |
| Fbxl16 | ST, RR, QTc, HR_TTE ↑ HR_TTE ↓, HRV ↑ | Unresponsive to tactile stimuli | Attention deficit hyperactivity disorder |
| Atn1 | rMSSD, HRV ↑ | Limb grasping, decreased exploration of novelty | Limited or no NPD annotations |
| Lpin3 | HR ↓,RR ↑ | No | Limited or no NPD annotations |
| Dnase1l2 | HR ↓,RR ↑,LVIDd, LVIDs ↓ | Abnormal vocalisation, decreased grip strength, abnormal motor capabilities/coordination/movement, hypoactivity, small superior vagus ganglion | Limited or no NPD annotations |
| Spred3 | HRV ↑ | Increased freezing behavior, decreased prepulse inhibition | Limited or no NPD annotations |
| Grm7 | HR ↓,RR ↑ | Hyperactivity, increased grip, decreased anxiety-related behavior, limb grasping | Recurrent major depressive disorder, Clozapine-induced agranulocytosis/granulocytopenia in treatment-resistant schizophrenia, Personality traits in bipolar disorder, Major depressive disorder (broad), Panic disorder, Neurodevelopmental disorder with seizures, hypotonia, and brain abnormalities |
| Cyp27a1 | HR,QRS↓,RR ↑ | No | Limited or no NPD annotations |
| Agpat1 | HR ↓,rMSSD, RR, HRV ↑ | No | Clozapine-induced agranulocytosis/granulocytopenia in treatment-resistant schizophrenia, Autism spectrum disorder or schizophrenia |
| Ctsd | ST,RR ↑ | No | neuronal ceroid lipofuscinosis |
| P3h1 | HR ↓,RR ↑ | Decreased grip strength | Limited or no NPD annotations |
| Pnmt | QTc Dispersion, rMSSD ↑ | Increased startle response, decreased exploration of novel environment, decreased breath rate during sleep | Limited or no NPD annotations |
Table shows the top ECG genes with the highest expression in the cluster FF-ANS representing feedforward central autonomic network (CAN) brain structures from Allen Brain Atlas. Also shown are the ECG and behavioral phenotypes associated with the mouse knockout (KO) lines for each gene as well as the human neuropsychiatric disease annotations
HR heart rate, HRV heart rate variability, RR R-R interval, ST, QTc, QRS ST, QTc, QRS intervals in electrocardiogram (ECG), TTE transthoracic echocardiography, rMSSD root mean square of successive differences between heart beats, shaded indicates increased HR and/or decreased HRV phenotypes in the corresponding knockout mouse line in IMPC. Neuropsychiatric disease associations are italicised