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Trypthophan Hydroxylase 1 (TPH1)
| Variant | Association | Phenotype | Sample Information | Author |
|---|---|---|---|---|
| rs4537731 rs211105 rs1800532 rs1799913 rs7933505 | Genotypic: ns Allelic: ns Haplotypic: ns |
Suicide attempts among patients | 837 Scandinavian patients: schizophrenia (n = 734); schizoaffective disorder (n = 87);schizophreniform disorder (n = 16), according to ICD-10 (DK) or DSM-III-R/DSM-IV (NO and SE) | Saetre, 2009 |
| 1,473 controls | ||||
rs4537731 rs684302 rs211105 rs1800532 rs1799913 rs7933505 |
Haplotypic: +, ACGCCG in borderline personality disoder participants with a low IGT χ2[1, N = 42] = 5.4, p < 0.02 | Suicide attempts | Ethnicity: Caucasian, Stockholm County | Maurex, 2009 |
| Cases:42 women with borderline personality disorder (BPD) and a history of suicide attempts | ||||
| The Iowa Gambling Task (IGT) was used to examine (i) social decision-making in women | ||||
| TPH-1 haplotype displayed a significantly higher frequency in BPD participants with impaired decision making (35%), compared to BPD participants with normal scores (12%) |
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| A218C | Genotypic: ns | Suicide attempts | Ethnicity: Brazilian, mostly Caucasian | Viana, 2006 |
| Cases: n: 248 (F:106; 84 suicide attempters); mean age: 37.2±8.8 | ||||
| Nonpsychiatric controls: n: 63(F:27), mean age: 34.3±8.9 | ||||
| Notes: No association with lethality or suicide attempt method | ||||
G7180T C7065T G6526A A218C A779C |
Allelic: ns Genotypic: ns Haplotypic: several |
Suicide attempts | Ethnicity: Han Chinese | Liu, 2006 |
| Cases: suicide attempters: F:126, M:171, mean age: 46.10±13.41 | ||||
| Nonattempters: F:112, M:217;mean age: 43.22±12.27 and healthy controls: F:86, M:98; mean age: 42.85±14.46 | ||||
| Notes: TCAAA haplotype asociated with suicidal behavior & psychosis | ||||
rs4537731 rs684302 rs211105 rs1800532 rs1799913 rs7933505 |
Allelic: ns Genotypic:ns Haplotypic: several |
Suicide attempts | Ethnicity: Caucasian, Stockholm County |
|
| Cases: 95 omen with borderline diagnosis and suicide attempts: mean age: 30.5±8.1 | ||||
| 98 female, healthy, matched controls: mean age: 44.0±13.8 | ||||
| Notes: most strongly associated haplotypes mapping to region between promoter and intron 3; Bonferroni-adjusted analyses | ||||
A6526G G5806T A779C |
Allelic: ns Genotypic: ns Haplotypic: ns |
Suicide attempts | Ethnicity: German, M: 258 (mean age: 42.6±9.6); F: 63 (mean age: 42.8±9.8) | Koller, 2005 |
| Cases: 80 alcohol-dependent patients with suicide attempt history (F:63) | ||||
| Controls: 241 alcohol-dependent without suicide attempt history | ||||
| Notes: no association between haplotypes and the number of suicide attempts | ||||
| A218C | Allelic: ns Genotypic: ns |
Suicide reattempts | Ethnicity: West Europe, Caucasian | Courtet, 2004 |
| Cases: suicide attempters: 103 (repeaters: F:17(85%), mean age: 34.05 ±11.71; nonrepeaters: F:47 (84%), mean age: 37.89±14.42) | ||||
| Notes: SS genotypes more impulsive | ||||
| A218C | Allelic: ns Genotypic:ns | Suicide attempts | Ethnicity: German | Rujescu,2003 |
| Cases: suicide attempters: n:147 (F:95, 54 violent attempters); mean age:40±14 | ||||
| Healthy controls with no family or personal history of Axis I or II diseases or mental disorder: F:178, M:148;mean age:46±15 | ||||
| Notes: their metanalysis showed overrepresentation of A218 allele (OR: 1.33, 95% CI: 1.17-1.50) and genotypes (OR:1.48, 95% CI: 1.22-1.79) in Caucasian suicide attempters and victims | ||||
A218C A779C |
Allelic: ns Genotypic: ns |
Suicide attempts | Ethnicity: German | Rujescu, 2002 |
| Cases: suicide attempters: F:59, M:27, mean age: 39.0±15 | ||||
| Healthy volunteers: F:88, M:66, mean age: 48.0±16 | ||||
| Notes: U allele carriers in attempters exhibited anger-related traits; interaction found between genotype and diagnosis | ||||
| A218C | Allelic: ns Genotypic: ns |
Violent suicide attempts | Nationality: Belgium (n:120), Bulgaria(n:113), Croatia (n:102), Germany(n:61), Greece (n:46), Israel (n:88), Italy (n:130), Sweden (n:83), the UK (n:184) | Souery,2001 |
| Cases: 527 bipolar and 400 unipolar depressive patients, including 167 suicide attempters (48 violent attempters) | ||||
| Sex, age, and ethnogeographically matched controls (n:927) | ||||
| Notes: lower CC frequency in unipolar depressive attempters; no association with depressive disorders; Bonferroni-adjusted | ||||
| Introns 7-9 | Allelic: +, 1, OR:1.54 95% CI 1.19-1.98 Genotypic:+,11, OR:2.49 5% CI 1.43-4.33 |
Suicide attempts
|
Cases: suicide attempters:F:126, mean age: 36.20±14.15; M:105, mean age:35.90±13.04; violent attempters (75.32%) | Abbar, 2001 |
Allelic: +, 1, OR:1.85 95% CI 1.23-2.77 Genotypic:+,11, OR:3.69 5% CI 1.64-8.29
|
Violent suicide attempts | Non-attempting controls with no family history of attempts or selected diagnoses:F:111; M:170; mean age:43.07±8.67 | ||
| Notes: highest ORs associated with violent suicide attempts with MDD history; Bonferroni adjusted | ||||
T1606C T3792A Intron 3; 217 |
Allelic: ns Genotypic: ns |
Suicide attempts | ||
| 3` region (CT)m(CA)n(CT)p | Allelic: +, 194, OR:1.61 95% CI 1.24-2.09; |
Violent suicide attempts | ||
| Genotypic:+, 194/194, OR:2.00 95% CI 1.18-3.41 | ||||
| Haplotypic: multiple | Violent suicide attempts | |||
| A218C | Genotypic: ns | Suicide attempts | Ethnicity: Han Chinese, Taiwan | Hong, 2001 |
| Cases: schizophrenic inpatients: n:196(F:54%), mean age: 35.3±12.1 | ||||
| Nonpsychiatric controls: n:251(F:51%), mean age: 33.8±7.4 | ||||
| Notes: 218A allele and genotypes associated with schizophrenia | ||||
| A218C | Allelic: ns | Suicide attempts | Cases: recent adolescent suicide attempters: F:48, M:40, mean age: 17.4±2.3; 84 Jewish (56% Askhenazi, 39% NonAshkenazi), and 4 (5%) Muslim participants | Zalsman, 2001 |
| Controls 1: probands’ parent(s) (80 trios and12 duos: n:92); 2: healthy Jewish controls from another study (n:172; 112 (65%) Askhenazi, 60 Non-Ashkenazi Jews; mean age: 40.9±10.30) | ||||
| Notes: used haplotype relative risk and TDT methods | ||||
intron 7 RFLP |
Genotypic: ns | Suicide attempts | Ethnicity: English, Caucasian | Ho, 2000 |
Cases: bipolar (M:58, F: 73) and unipolar patients (M:53, F: 86) |
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| Notes: uncorrected for multiple testing | ||||
| A218C | Allelic: +, C, OR:2.12 95% CI 1.18-3.82 | Suicide attempts | Ethnicity: Korean | Paik, 2000 |
| Schizophrenic patients:M:107, F:110; mean age: 30.0±9.0, including 27 suicide attempters | ||||
| Healthy controls: F:112, M:124; mean age: 29.6±3 | ||||
| Genotypic: +, CC, OR:3.01 5% CI 1.23-7.33 | Notes: no association with schizophrenia | |||
| A218C | Allelic: ns Genotypic: ns |
Suicide attempts | Ethnicity: European Caucasian, mostly Swedish | Geijer, 2000 |
| Cases: suicide attempters: F:108, M:57; mean age: 41±17 | ||||
| Nonpsychiatric controls: n:99 (F:95, mean age: 38±6) | ||||
| Notes: pooling with TPH data from previous studies showed a significant association of allele A and attempts | ||||
| A218C | Allelic:+, A, p=.015 | Suicide attempts | Ethnicity: Chinese | Tsai, 1999 |
| Cases: bipolar (F:50, M:33) and major-depressive patients (F:44, M:24; mean age: 36.8±1) | ||||
| Healthy controls: F:109, M:91;mean age: 36.4±0.4) | ||||
| Genotypic: +, AA, in major-depressive patients, p=.031 | Notes: A genotypes associated with major depression | |||
A779C A218C |
Allelic: ns Genotypic: ns |
Suicide attempts | Ethnicity: Japanese | Kunugi, 1999 |
| Cases: patients with bipolar [n:141(F:88); mean age: 46.7±13.8] or unipolar major depression [n:73 (F:48); mean age: 55.0±14.6], including suicide attempters: n:46 (F:37); mean age:45.7±12.8] | ||||
| Healthy controls: n:208 (F:113); mean age:32.1±13.3 | ||||
| Notes: no association either with uni- or bipolar depression | ||||
T7180G C7065T G5806T |
Allelic: ns Genotypic: ns |
Suicide attempts | Cases: violent offender males: impulsive (n:113) and nonimpulsive (n:54), including 97 suicide attempters | Rotondo, 1999 |
| Notes: 1. Screening for TPH promoter variants: n:260 [Caucasian: Italian (n:69), American (n:65), Finnish (n:126) 2. Genotyping for A6526G: n:772 [Caucasian: Finish (n:320), Italian (n:237), American (n:174), Southwest American Indians (n:41); 3. Estimating linkage disequilibrium of A6526G and TPH IVS7+C779A: Finnish male offenders (n:167), 153 Finnish controls, Italian controls (n:84), Southwest American Indians (n:41); applied correction for multiple tests | ||||
| A6526G | Allelic: +,G, impulsive (p<0.0002) & pooled (p<0.0006) offenders | |||
| Genotypic: +, G-, impulsive (p<0.0003) & pooled offenders (p<0.0016) | ||||
| IVS7+C779A | Allelic: +, C779, p<.0003 in offenders & p<0.0002 in impulsive offenders Genotypic: +, C779C, in impulsive (p<0.0001), nonimpulsive (p<0.017), pooled offenders (p<0.0008) | |||
| Haplotypic:+, (IVS7+C779, 6526G), impulsive (p<0.0009) and pooled offenders (p<0.0003) | ||||
| A218C | Allelic: ns Genotypic: ns |
Suicide attempts | Ethnicity: French | Bellivier, 1998 |
| Cases: patients with bipolar disorder(F:84, M:68; mean age:46.9±15.3; attempters: N:52) | ||||
| Healthy controls with no personal or family history of suicide attempts or mood disorders (F:37,M:57;mean age:43.7±5.6) | ||||
| Notes: no association with the violence of the method; Significant association with manic depression | ||||
| A779C | Replication: Genotypic: +,779C carriers, impulsive offenders, Cramer V=.34; Combined sample: Genotypic: +,779C carriers, impulsive offenders, Cramer V=.34 | Suicide attempts | Cases: alcoholic violent offenders [185 males; mean age:31±10; impulsive (n:122)] and combined sample [offenders: 268 males; mean age: 31±9; impulsive (n:168)] | Nielsen, 1998 |
| Replication: Genotypic: -,779C carriers, (Cramer V=.33), nonimpulsive group; Combined sample: Genotypic: +,779C carriers, pooled offenders (Cramer V=.18) | Suicide attempts | Matched controls [236 males; mean age:32±11); Relatives of offenders or controls: n:280 [M:60%; mean age:42±15); Combined controls (n:256;mean age:32±11) | ||
| Replication: Genotypic: +,779C carriers, (Cramer V=.39); Combined sample: Genotypic: +,779C carriers, impulsive, non-impulsive, and pooled offenders (Cramer V=.37, .29, .20), respectively | Severe suicide attempts | Notes: the variant also associated with alcoholism & socialization | ||
| A218C | Allelic: ns Genotypic: ns |
Suicide attempts | Ethnicity: East Anglian, English Caucasian | Furlong, 1998 |
| Cases: Patients with bipolar disorder: F:63, M:55, attempters:56 OR unipolar depression: F:78, M:47, attempters:69 | ||||
| Healthy controls: F:225, M: 212 | ||||
| Notes: Bonferroni adjusted; no association with affective disorders. | ||||
| A779C | Allelic: +, U, p<.009 | Suicide attempts | Ethnicity: Caucasian, European | Mann, 1997 |
| Cases: patients with major depression with 29 suicide attempters (F:55%; mean age:35.3±14) and 22 nonattempters (F:73%; mean age:41.0±16.6) | ||||
| Notes: analyses adjusted for depression and presence of borderline personality disorder; depression more severe in LL and UL genotypes | ||||
| Genotypic: +, UU, OR=12.5, 95% 1.6-142.9 | ||||
| Ava II | Genotypic:ns | Suicide attempts | Ethnicity: Caucasian, European origin | Abbar, 1995 |
| Cases: Suicide attempters (M:31, mean age:31.5±11.8; F:31, mean age:36.1±12.2) | ||||
| Healthy controls: n:52 (F:24);mean age:52.9±18.9 | ||||
| Notes: no association with suicide intent, onset, number, and violence of suicide attempts | ||||
| Intron 7 | Genotypic: -,UU, p=.016 | Suicide attempts | Ethnicity: Finnish, Caucasian | Nielsen, 1994 |
| Cases: Impulsive (n:56;mean age:30±1) and non-impulsive (n: 14; mean age:31±2) alcoholic violent offenders, including 36 suicide attempters | ||||
| 20 controls without mental diagnoses (mean age: 33±2) | ||||
| Allelic: +, L | Repeated suicide attempts | Notes: no association with impulsive behavior | ||
| A218C | Allelic: ns (comparison 1 or 2) | Suicide | Ethnicity: Croatian, Slavic | Stefulj, 2006 |
| Genotypic: +, CC, in individuals over 65 , OR 2.77 95% CI 1.25-6.16 (comparison 1) | Completed suicides: n: 247 (all males; 74 above 65 years of age); | |||
| Genotypic: +, CC, OR 2.44 95% CI 1.46-4.08 (comparison 2) | Nonpsychiatric controls: n:278 (42 above 65 years of age) | |||
| Notes: Bonferoni-adjusted analyses; Older suicides compared to age-stratified (comparison 1) or the entire control group (comparison 2) | ||||
C7065T A218C |
Allelic: ns Genotypic: ns Haplotypic: ns |
Violent suicide | Ethnicity: Croatian/Slavic | Stefulj, 2005 |
| Cases: 160 violent male suicides (mean age:48±19) | ||||
| Nonpsychiatric controls: 284 male controls (mean age: 44±13) | ||||
| Notes: the two loci are in LD; Bonferroni-adjusted | ||||
| A218C | Combined CC and 1010 (SLC6A4-VNTR2) genotypes: +, p=.00156
|
Suicide | Ethnicity: Croatian | Jernej, 2004 |
| Cases: 192 suicides: F: 25%,mean age:52±19 | ||||
| 377 nonpsychiatric controls: F:21%,mean age:43±12 | ||||
| Notes: examined combinations of suspected risk genotypes (SLC6A4's VNTR2 1010 & TPH's CC); Found a dose effect: carriers of either CC or 1010 genotypes [OR:1.45 95%CI:1.0-2.1]; Carriers of both CC & 1010 genotypes [OR:2.57 95%CI:1.2-5.4] | ||||
A779C A218C |
Allelic: ns Genotypic: ns |
Suicide | Ethnicity: Japanese | Ohtani, 2004 |
| Cases: suicide completers (F:39,mean age ± SD, 63.5±16.2; M: 95,mean age ± SD, 55.4±16.1) | ||||
| Healthy controls: F:154, mean age ± SD: 48.9±15.9; M: 171, mean age ± SD: 48.1±14.8 | ||||
| A779C | Allelic: +, C, p=.045 | Suicide | Ethnicity: Swedish | Roy, 2001 |
| Cases: surviving MZ co-twins of suicide completers:F:9, M:15; mean age: 68.8±8.8 | ||||
| General population controls:F:81, M:77; mean age:56.7±15.8 | ||||
| Genotypic: ns | ||||
A6526G G5806T A218C |
Allelic: ns Genotypic: ns |
Suicide | Cases: Suicide completers: n:101, mean age: 32.20±9.38 | Turecki, 2001 |
| Healthy volunteers: n:129, mean age: 34±10.56 | ||||
| Notes: associated haplotype especially prevalent in violent (38.17%) relative to non-violent suicides (25%); corrected for multiple testing | ||||
Haplotypic:+,6526G-5806T-218C, OR 2.0 CI: 1.3-3.6 |
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| A6526GA218C | Allelic: ns Genotypic: ns |
Suicide | Ethnicity: Japanese | Ono, 2000 |
| Suicide completers: F:42, M:90; mean age:48.3±18.0 | ||||
| Healthy controls: F:42, M:90; mean age:47.2±15.7 | ||||
A218C A779C |
Allelic: ns Genotypic: ns |
Suicide | Ethnicity: Caucasian, Utah | |
| Recent male suicide completers: n: 47 (14 between 10-21 and 33 cases betwen 22-31 years of age) | ||||
| Controls: variant frequencies used from two previous studies | ||||
| Notes: no association even if cases stratified by age or method | ||||
| A218C | Allelic: ns Genotypic: ns |
Suicide | Geographic origin: Budapest | Faludi, 2000 |
| Cases: depressed suicide completers: N:32 | ||||
| Controls dying of causes unrelated to central nervous system: N:57 | ||||
| A218C | Allelic: ns Genotypic: ns |
Suicidal ideation | Ethnicity: White Caucasian, 75% West European | Du, 2001 |
| Cases: patients with major depression: F:79, M:56, mean age: 40.08±9.43 | ||||
| Unrelated controls: F:108; M:88, mean age: 36.26±12.12 | ||||
| Bonferroni adjusted; AA genotypes had highest somatic anxiety scores |
Notes: += positive,significant; - =negative,significant; ns= nonsignificant; F=females; M=males; A218C=rs1800532, A779C=rs1799913