Table 1.
Top Anxiety Biomarkers: Convergent Functional Evidence (CFE).
| Symbol/Gene Name | Probesets | Step 1 Discovery (Direction of Change in High Anxiety) Method/ Score/% | Step 2 Prioritization Convergent Functional Genomics (CFG) Evidence For Involvement in Anxiety Score | Step 3 Validation ANOVA p-value/Score | Step 4 Significant Predictions of High Anxiety State ROC AUC/ p-value 3 pts ALL 2pts Gender 1pts Gender /Dx | Step 4 Significant Predictions of High STAI State ROC AUC/ p-value 3 pts ALL 2pts Gender 1pts Gender /Dx | Step 4 Significant Prediction of First Year Hosp. for Anxiety ROC AUC/p-value 3 pts ALL 2pts Gender 1pts Gender/Dx | Step 4 Significant Predictions of Future Hosp for Anxiety OR/p-value 3 pts ALL 2pts Gender 1pts Gender /Dx | Other Psychiatric and Related Disorders Evidence | Drugs that Modulate the Biomarker in Opposite Direction to High Anxiety | CFE Polyevidence Score for Involvement in Anxiety (Based on Steps 1–4) |
|---|---|---|---|---|---|---|---|---|---|---|---|
|
GAD1 Glutamate Decarboxylase 1 |
205278_at |
(I) DE/4 62.3% |
11 |
6.79E-01/0 Not Stepwise |
ALL C: (42/486) 0.58/3.94E-02 Gender Females C: (17/88) 0.65/2.75E-02 Gender-dx F-PSYCHOSIS C: (5/28) 0.77/2.94E-02 F-SZ C: (4/8) 0.94/2.17E-02 |
Gender-dx M-PSYCHOSIS C: (7/74) 0.69/4.73E-02 M-SZA C: (3/32) 0.79/4.96E-02 |
ALL C: (70/318) 1.3/5.52E-03 Gender Males C: (59/273) 1.34/2.80E-03 Gender-dx M-BP C: (13/96) 1.69/2.12E-02 M-PSYCHOSIS C: (37/121) 1.33/9.36E-03 M-SZA C: (23/58) 1.58/9.14E-03 |
Alcohol Withdrawal Autism BP Depression Intellectual Disability MDD Mood Disorders NOS Phencyclidine PTSD Suicide SZ |
Carbamazepine Lithium Omega-3 fatty acids Valproate |
22 | |
|
NTRK3 Neurotrophic Receptor Tyrosine Kinase 3 |
215311_at |
(I) DE/4 53.2% |
4 |
3.26E-01/2 Stepwise |
Gender Males L: (4/246) 0.77/2.98E-02 Gender-dx M-PSYCHOSIS L: (2/102) 0.9/2.83E-02 M-SZA L: (2/46) 0.85/4.75E-02 |
ALL C: (42/486) 0.59/3.04E-02 L: (21/291) 0.61/4.83E-02 Gender Females C: (17/88) 0.68/1.20E-02 L: (10/52) 0.7/2.85E-02 Gender-dx F-BP C: (4/31) 0.89/6.66E-03 M-MDD L: (4/31) 0.82/1.96E-02 |
Gender-dx F-PSYCHOSIS C: (2/13) 0.91/3.78E-02 Gender-dx F-SZA C: (2/6) 1/3.20E-02 |
ALL C: (70/318) 1.23/9.38E-03 Gender Females C: (11/45) 1.84/1.60E-02 |
Aging Alcohol Alzheimer’s Disease Bipolar II BP Longevity MDD Mood Disorders NOS Pain PTSD Risky Behavior SAD Social Isolation Stress Subsyndromal symptomatic depression Suicide SZ |
Clozapine | 19 |
|
ADRA2A Adrenoceptor Alpha 2A |
209869_at |
(I) AP/4 50% |
4 |
9.07E-01/0 Not Stepwise |
Gender-dx M-MDD C: (2/57) 0.88/3.43E-02 |
Gender Females C: (17/88) 0.63/4.91E-02 F-SZ C: (4/8) 0.88/4.07E-02 L: (3/5) 1/4.16E-02 |
ALL C: (18/236) 0.65/1.80E-02 Gender Males C: (15/199) 0.67/1.44E-02 Gender-dx M-PSYCHOSIS C: (7/74) 0.81/3.22E-03 M-PTSD C: (3/10) 0.86/4.37E-02 M-SZ C: (4/42) 0.91/3.47E-03 |
ALL C: (70/318) 1.41/4.65E-04 Gender Males C: (59/273) 1.44/5.74E-04 Gender-dx M-PSYCHOSIS C: (37/121) 1.52/3.60E-03 M-PTSD C: (5/12) 2.59/2.08E-02 M-SZ C: (14/63) 2.14/1.61E-04 |
Alcohol Bipolar COVID-19 Depression MDD Pain PTSD Suicide SZ |
Carbamazepine Clozapine Norfluoxetine Valproate |
17 |
|
FZD10 Frizzled Class Receptor 10 |
219764_at |
(I) DE/4 53.2% |
2 |
3.57E-01/2 Stepwise |
ALL C: (42/486) 0.6/1.39E-02 L: (21/291) 0.64/1.43E-02 Gender Females C: (17/88) 0.69/7.42E-03 L: (10/52) 0.68/3.88E-02 F-BP C: (4/31) 0.85/1.26E-02 F-SZA C: (1/20) 1/4.97E-02 F-SZ L: (3/5) 1/4.16E-02 |
ALL C: (18/236) 0.67/7.66E-03 Gender Males C: (15/199) 0.68/1.22E-02 L: (4/113) 0.75/4.52E-02 Gender-dx M-PSYCHOSIS C: (7/74) 0.75/1.64E-02 L: (1/39) 1/4.57E-02 M-SZ C: (4/42) 0.87/8.21E-03 L: (1/22) 1/4.90E-02 |
ALL C: (70/318) 1.34/3.63E-03 Gender Males C: (59/273) 1.34/6.61E-03 Gender-dx M-PSYCHOSIS C: (37/121) 1.55/2.70E-03 M-SZ C: (14/63) 1.92/5.16E-03 |
Alcohol Alzheimer’s BP Circadian abnormalities MDD PTSD |
Aripiprazole Fluoxetine Gamma Frequency |
17 | |
|
GRK4 G Protein-Coupled Receptor Kinase 4 |
210600_s_at |
(I) DE/6 81.8% |
0 |
3.40E-01/2 Stepwise |
Gender-dx M-MDD C: (2/57) 0.87/3.77E-02 |
Gender Females C: (17/88) 0.64/3.26E-02 Gender-dx F-BP C: (4/31) 0.86/1.08E-02 M-MDD L: (4/31) 0.85/1.26E-02 |
ALL C: (18/236) 0.62/4.27E-02 Gender Males C: (15/199) 0.64/4.06E-02 |
ALL C: (70/318) 1.32/4.46E-03 Gender Males C: (59/273) 1.32/8.99E-03 Gender-dx F-MDD C: (2/15) 1.87/4.51E-02 Gender-dx M-PSYCHOSIS C: (37/121) 1.34/2.11E-02 |
Autism Bipolar Cannabis Depression PTSD Stress |
Clozapine Gamma Frequency |
17 |
|
ATP1B2 ATPase Na+/K+ Transporting Subunit Beta 2 |
204311_at |
(I) DE/2 39% |
4 |
1.65E-01/2 Stepwise |
Gender-dx M-MDD C: (2/57) 0.9/2.81E-02 |
Gender Females C: (17/88) 0.64/3.75E-02 Gender-dx F-BP C: (4/31) 0.84/1.46E-02 F-PSYCHOSIS C: (5/28) 0.77/3.37E-02 |
Gender Males C: (15/199) 0.63/4.18E-02 Gender-dx M-PSYCHOSIS C: (7/74) 0.79/5.55E-03 M-PTSD C: (3/10) 0.86/4.37E-02 M-SZ C: (4/42) 0.86/9.22E-03 |
ALL C: (70/318) 1.59/1.91E-05 Gender Females C: (11/45) 1.68/2.97E-02 Males C: (59/273) 1.56/1.33E-04 Gender-dx F-MDD C: (2/15) 3.16/3.10E-02 M-BP C: (13/96) 1.61/1.79E-02 M-PSYCHOSIS C: (37/121) 1.98/4.84E-05 M-SZ C: (14/63) 2.39/7.75E-04 M-SZA C: (23/58) 1.68/1.24E-02 |
Alcohol Alzheimer’s MDD PTSD Stress Substance Abuse Suicide SZ |
Acetyldigitoxin Clozapine Deslanoside Digitoxin Digoxin Haloperidol Lithium Valproate |
16 |
|
CLIC6 Chloride Intracellular Channel 6 |
242913_at |
(I) AP/6 84.2% |
2 |
5.06E-01/0 Not Stepwise |
Gender Females C: (17/88) 0.67/1.68E-02 Gender-dx F-BP C: (4/31) 0.8/2.97E-02 F-PSYCHOSIS C: (5/28) 0.85/8.20E-03 F-SZ C: (4/8) 0.97/1.47E-02 F-SZA C: (1/20) 1/4.97E-02 |
ALL C: (18/236) 0.62/4.11E-02 Gender-dx M-PSYCHOSIS C: (7/74) 0.71/3.17E-02 Gender-dx M-SZ C: (4/42) 0.8/2.44E-02 |
ALL C: (70/318) 1.32/6.89E-03 Gender Females C: (11/45) 1.59/4.32E-02 Males C: (59/273) 1.27/2.51E-02 Gender-dx M-SZ C: (14/63) 1.68/1.04E-02 |
Aging Alcohol Cocaine MDD Phencyclidine Restraint Stress Suicide |
Clozapine Omega-3 fatty acids Gamma Frequency |
16 | |
|
EFNA5 Ephrin A5 |
1559360_at |
(I) DE/6 80.5% (I) AP/4 51.3% |
2 |
2.02E-04/4 Nominal |
Gender Females C: (17/88) 0.63/4.85E-02 Gender-dx M-SZ C: (6/90) 0.71/4.03E-02 |
ALL L: (5/133) 0.74/3.34E-02 Gender Males L: (4/113) 0.75/4.67E-02 Gender-dx F-SZA C: (2/6) 1/3.20E-02 M-SZA C: (3/32) 0.79/4.96E-02 |
Gender-dx M-BP C: (13/96) 1.41/2.92E-02 |
Alcohol Alzheimer’s BP Cannabis Chronic Fatigue Syndrome Depression Insomnia Intellect Longevity MDD Morphine Pain Stress Suicide SZ |
Omega-3 fatty acids Gamma Frequency |
18 | |
|
GPX7 Glutathione Peroxidase 7 |
213170_at |
(D) DE/4 64.3% |
2 |
4.64E-01/2 Stepwise |
ALL C: (19/495) 0.63/2.63E-02 |
Gender-dx F-BP C: (4/31) 0.86/1.08E-02 F-SZA C: (1/20) 1/4.97E-02 M-MDD L: (4/31) 0.86/1.08E-02 |
Gender-dx M-PSYCHOSIS C: (7/74) 0.71/3.17E-02 M-SZ C: (4/42) 0.82/1.99E-02 |
ALL C: (70/318) 1.42/6.50E-03 Gender Males C: (59/273) 1.47/7.12E-03 Gender-dx M-PSYCHOSIS C: (37/121) 1.5/2.40E-02 M-SZ C: (14/63) 1.9/4.95E-02 |
Aging MDD Neuropathic pain SZA |
Mianserin S-adenosyl methionine (SAM) |
16 |
|
NTRK3 Neurotrophic Receptor Tyrosine Kinase 3 |
215025_at |
(I) DE/2 35.1% |
4 |
6.58E-01/2 Stepwise |
Gender-dx M-BP L: (2/93) 0.9/2.83E-02 |
ALL C: (42/486) 0.61/9.05E-03 L: (21/291) 0.64/1.43E-02 Gender Females C: (17/88) 0.72/2.51E-03 Males L: (11/239) 0.67/2.55E-02 Gender-dx F-BP C: (4/31) 0.86/1.08E-02 F-PSYCHOSIS C: (5/28) 0.77/2.93E-02 F-SZ C: (4/8) 0.94/1.92E-02 M-BP L: (2/92) 0.93/1.84E-02 |
Gender-dx M-PSYCHOSIS C: (7/74) 0.7/4.55E-02 Gender-dx M-SZ C: (4/42) 0.82/1.99E-02 L: (1/22) 1/4.90E-02 |
ALL C: (70/318) 1.36/5.70E-03 Gender Males C: (59/273) 1.4/4.76E-03 Gender-dx M-BP C: (13/96) 1.95/1.24E-02 M-PSYCHOSIS C: (37/121) 1.4/1.87E-02 M-SZ C: (14/63) 1.93/3.78E-03 |
Aging Alcohol Alzheimer’s Disease Bipolar I BP Depression Longevity MDD Mood Disorders NOS Pain PTSD Risky Behavior SAD Social Isolation Stress Subsyndromal symptomatic depression Suicide SZ |
Clozapine | 16 |
|
SLC6A2 Solute Carrier Family 6 Member 2 |
217214_s_at |
(I) DE/2 40.3% |
4 |
3.40E-01/2 Stepwise |
Gender-dx F-PSYCHOSIS L: (4/17) 0.81/3.50E-02 F-SZA L: (4/12) 0.81/4.47E-02 |
ALL C: (42/486) 0.63/2.37E-03 L: (21/291) 0.62/3.78E-02 Gender Females C: (17/88) 0.76/4.78E-04 Gender-dx F-MDD C: (7/21) 0.77/2.62E-02 F-PSYCHOSIS C: (5/28) 0.8/1.92E-02 F-SZ C: (4/8) 0.94/2.17E-02 M-SZ C: (6/90) 0.71/4.63E-02 |
Gender-dx M-PSYCHOSIS C: (7/74) 0.72/2.92E-02 M-SZA C: (3/32) 0.87/1.78E-02 M-PSYCHOSIS L: (1/39) 1/4.57E-02 M-SZ L: (1/22) 1/4.90E-02 |
ALL C: (70/318) 1.33/4.74E-03 Gender Males C: (59/273) 1.34/6.73E-03 Gender-dx M-BP C: (13/96) 1.61/4.50E-02 M-PSYCHOSIS C: (37/121) 1.31/2.54E-02 |
Alcohol Depression MDD Postpartum Depression PTSD Suicide |
Fluoxetine Norfluoxetine | 16 |
|
SLC6A4 Solute Carrier Family 6 Member 4 |
242009_at |
(I) DE/2 35.1% |
10 |
8.51E-01/0 Not Stepwise |
Gender-dx F-PSYCHOSIS C: (2/13) 0.91/3.76E-02 F-SZA C: (2/6) 1/3.20E-02 M-PTSD C: (3/10) 0.86/4.37E-02 M-SZ C: (4/42) 0.76/4.74E-02 |
ALL C: (70/318) 1.21/1.15E-02 Gender Males C: (59/273) 1.19/2.77E-02 Gender-dx M-PTSD C: (5/12) 2.54/3.24E-02 |
Aging Alcohol Anxiety BPD Depression Early Life Stress MDD MSK Neuropathic pain Pain Postpartum Depression PTSD Stress Suicide |
Agomelatine Benzodiazepines Citalopram Clozapine Omega-3 fatty acids Oxycodone Sertraline Vortioxetine |
16 | ||
|
TMEM138 Transmembrane Protein 138 |
223113_at |
(D) DE/4 63% |
4 |
8.63E-01/0 Not Stepwise |
Gender Males L: (11/239) 0.66/4.12E-02 Gender-dx F-BP C: (4/31) 0.86/1.08E-02 |
ALL L: (5/129) 0.72/4.61E-02 Gender-dx M-PTSD C: (3/10) 0.86/4.37E-02 |
ALL C: (70/318) 1.3/1.46E-02 Gender Males C: (59/273) 1.34/1.20E-02 Gender-dx M-PSYCHOSIS C: (37/121) 1.5/6.57E-03 M-PTSD C: (5/12) 3.71/4.13E-02 M-SZA C: (23/58) 1.51/2.83E-02 |
Alcohol Brain arousal Depression |
Antidepressants | 16 | |
|
ANKRD28 Ankyrin Repeat Domain 28 |
229307_at |
(I) DE/6 80.5% |
0 |
6.20E-01/2 Stepwise |
ALL C: (42/486) 0.62/5.30E-03 Gender Males C: (25/398) 0.72/1.31E-04 Gender-dx M-MDD C: (7/57) 0.89/3.97E-04 Gender-dx M-PSYCHOSIS C: (12/165) 0.72/5.72E-03 Gender-dx M-SZ C: (6/90) 0.84/3.13E-03 |
Gender-dx F-PSYCHOSIS C: (2/13) 0.91/3.76E-02 Gender-dx F-SZA C: (2/6) 1/3.20E-02 |
ALL C: (70/318) 1.22/2.96E-02 Gender-dx F-MDD C: (2/15) 3.09/3.59E-02 Gender Males C: (59/273) 1.21/4.06E-02 Gender-dx M-PSYCHOSIS C: (37/121) 1.42/7.30E-03 Gender-dx M-SZA C: (23/58) 1.61/1.24E-03 |
Alcohol ASD BP Childhood Trauma Depression MDD Mood instability PTSD Stress Suicide |
N/A | 15 | |
|
CCKBR Cholecystokinin B Receptor |
210381_s_at |
(I) DE/2 48% |
4 |
4.37E-01/2 Stepwise |
Gender-dx F-BP C: (4/31) 0.8/2.97E-02 Gender-dx M-BP C: (5/139) 0.74/3.70E-02 Gender-dx F-BP L: (3/18) 0.82/4.29E-02 |
ALL C: (18/236) 0.63/3.01E-02 Gender-dx F-PSYCHOSIS C: (2/13) 0.91/3.78E-02 Gender-dx F-SZA C: (2/6) 1/3.20E-02 Gender Males C: (15/199) 0.63/4.48E-02 Gender-dx M-PTSD C: (3/10) 0.86/4.37E-02 Gender-dx M-SZ C: (4/42) 0.76/4.74E-02 |
ALL C: (70/318) 1.33/4.28E-03 Gender Males C: (59/273) 1.32/9.50E-03 Gender-dx M-PSYCHOSIS C: (37/121) 1.3/3.14E-02 |
Alcohol BP Chronic Stress MDD Phencyclidine Suicide SZ |
Clozapine | 15 | |
|
DYNLL2 Dynein Light Chain LC8-Type 2 |
229106_at |
(D) DE/2 39.3% |
4 |
1.96E-01/2 Stepwise |
Gender Males L: (4/246) 0.78/2.79E-02 Gender-dx M-BP L: (2/93) 0.85/4.50E-02 |
Gender-dx F-SZA C: (1/20) 1/4.97E-02 |
ALL L: (5/129) 0.74/3.36E-02 |
Gender-dx M-SZA C: (23/58) 1.49/4.09E-02 |
Aging Alcohol Alzheimer’s Disease Methamphetamine Stress SZ |
Benzodiazepines Valproate |
15 |
| Hs.550187 | 240253_at |
(I) DE/6 88.3% |
0 |
2.74E-01/2 Stepwise |
Gender Females C: (17/88) 0.72/2.59E-02 Gender-dx F-BP C: (4/31) .84/1.46E-02 |
Gender Females C: (3/37) 0.8/4.23E-02 Gender-dx F-SZA C: (2/6) 1/3.20E-02 M-PSYCHOSIS C: (7/74) 0.71/3.44E-02 M-SZA C: (3/32) 0.9/1.29E-02 |
ALL C: (70/318) 1.19/3.48E-02 Gender-dx M-PSYCHOSIS C: (37/121) 1.23/2.54E-02 M-SZ C: (14/63) 1.27/3.90E-02 |
Suicide | N/A | 15 | |
|
NRG1 Neuregulin 1 |
208232_x_at |
(I) DE/4 65.8% |
4 |
6.66E-01/2 Stepwise |
Gender-dx M-MDD C: (2/57) 0.93/2.08E-02 M-BP L: (2/93) 0.85/4.50E-02 |
Gender-dx F-BP C: (4/31) 0.81/2.59E-02 Gender-dx M-PSYCHOSIS C: (12/165) 0.73/3.69E-03 M-SZ C: (6/90) 0.7/4.79E-02 M-SZA C: (6/75) 0.76/1.66E-02 |
ALL C: (70/318) 1.2/3.99E-02 Gender Males C: (59/273) 1.27/1.37E-02 Gender-dx M-BP C: (13/96) 1.66/1.80E-02 M-PSYCHOSIS C: (37/121) 1.25/4.26E-02 M-SZA C: (23/58) 1.32/4.07E-02 |
Aging Alcohol Alzheimer’s BP Chronic Stress Cocaine COVID-19 Depression Longevity MDD Memory Methamphetamine Psychosis PTSD Suicide SZ |
Ketamine Antipsychotics Valproate Lithium |
15 | |
|
TFRC Transferrin Receptor |
207332_s_at |
(D) DE/4 56% |
2.00 |
7.11E-01/2 Stepwise |
Gender Females L: (4/52) 0.82/1.66E-02 Gender-dx F-PSYCHOSIS C: (4/28) 0.77/4.39E-02 L: (4/17) 0.85/2.08E-02 F-SZA L: (4/12) 0.84/3.09E-02 |
Gender-dx F-BP C: (4/31) 0.88/7.85E-03 |
Gender-dx M-PTSD C: (3/10) 0.9/2.64E-02 |
ALL C: (70/318) 1.29/2.21E-02 Gender Males C: (59/273) 1.35/1.46E-02 Gender-dx M-SZA C: (23/58) 1.54/3.73E-02 |
Aging Alcohol Alzheimer’s BP Cocaine Depression Longevity MDD (Recurrent) Neuropathic Pain SZ |
Valproate | 15 |
After Step 4 Testing in independent cohorts for state and trait predictive ability. For Step 4 Predictions, C: -cross-sectional (using levels from one visit), L: -longitudinal (using levels and slopes from multiple visits). In ALL, by Gender, and personalized by Gender and Diagnosis (Gender/Dx). M-Males, F-Females. MDD-depression, BP-bipolar, SZ-schizophrenia, SZA-schizoaffective, PSYCHOSIS- schizophrenia and schizoaffective combined, PTSD-post-traumatic stress disorder.