Table 1.
Main Previous Findings about the Genetics of Suicide Behavior in Affective Disorders.
| References | Sample | Main Findings | Type of Study |
|---|---|---|---|
| [16] | 79 individuals with bipolar I 30 individuals with bipolar II 86 healthy controls |
No association between bipolar disorder and the SERT gene. No association was found between suicidal behavior and the SERT gene. | Candidate gene, cases and controls |
| [17] | 67 individuals with depressive disorders 28 individuals with bipolar disorder 106 healthy controls |
No association between the 5-HT2A polymorphism 1438G/A and the patient group or suicide attempts. | Candidate gene, cases and controls |
| [18] | 46 individuals with depressive disorders 34 individuals with bipolar disorder 92 healthy controls |
No association between the serotonin transporter polymorphism in SLC6A4 gene and mood disorders or suicide attempts. | Candidate gene, cases and controls |
| [19] | 70 individuals with a history of suicide attempts and various psychiatric disorders 42 individuals with MDD 10 individuals with bipolar disorder 97 healthy controls |
No association between the G2457A polymorphism in ABCG1 gene and affective disorders or suicidal behavior. | Candidate gene, cases and controls |
| [20] | 2025 affected relative pairs with depressive disorders and mood disorders | Significant association between regions at 2p, 5q, 6q, 11q and Xq and suicide attempt. Strongest evidence for the phenotype Depression Spectrum Disorder was found at D8S1145 marker at 8p22-p21. Significant association between recurrent, early-onset major depressive disorder (RE-MDD) and Xq at DXS1047 marker. For all depressive phenotypes significant correlation with D8S1145 and suicide attempt. | Genome-wide linkage |
| [21] | 9265 individuals, probands with alcohol dependence and biological relatives | Significant association for the phenotype “ever tried suicide” and chromosome 2 near D2S1790. Some association between the quantitative suicidality index and chromosome 1 near D1S1602, and chromosome 3 near D1S1602. | Genome-wide linkage |
| [22] | 106 individuals with completed suicide and MDD or depression not otherwise specified 152 controls with MDD |
The variants 5-HTTLPR and STin2 in 5-HTT were considered. A significant association was found between suicide completion and having at least one copy of the STin2 10 allele. Added a positive family history of suicide risk increases the risk of suicide 5.56 times after adjustment for other clinical risk factors. |
Candidate gene, cases and controls |
| [23] | 1060 individuals with bipolar disorder from 154 multiplex families | Genome-wide significance between 6q25.2 at D6S2436 and suicidal behavior. Suggestive linkage was observed on 2q24.1 at D2S1353, 4p16.1 at D4S2366, 6q24.3 at D6S1848 and 10q25.3 at D10S1237. | Genome-wide linkage |
| [24] | 162 individuals, multiplex bipolar pedigrees | Suggestive linkage signal between 2p12 and suicide attempt; from D2S1394 on 2p13 to D2S2972 on 2q11, including TACR1 and TGOLN2. The second suggestive association was found at 6q26 at D6S1277. |
Genome-wide linkage |
| [25] | 154 individuals with MDD 154 healthy, age and gender matched controls |
No association between the Val66Met polymorphism of the BDNF and development of MDD. Significant association between the dose of the Met allele and the clinical features psychotic and suicidal behavior, which suggest association with severe MDD. |
Candidate gene, cases and controls |
| [26] | 3117 individuals with bipolar disorder 1273 individuals with MDD |
Suicide attempts in the bipolar sample were associated with following SNPs: rs1466846 (TBL1XR1), rs924134 (IRX2), rs6548036 (CAPN13), rs1457463 (ZNF409), rs11130703 (FLJ42117). Suicide attempts in the MDD sample were associated with following SNPs: rs2576377 (ABI3BP), rs2601098 (SLC4A4), rs1417259 (LRRC44), rs7655668 (SLC4A4), rs12462673 (HAS1), rs6737169 (ARL6IP2). None of these results were replicated. Modest support was found for candidate genes FKBP5 and NGFR (p75NTR). |
Genome-wide association study |
| [27] | 2023 individuals with MDD | The quantitative SSU score showed suggested association for rs4751955 (GFRA1). For the discrete trait of serious suicidal attempts suggested association was found at rs203136 (KIAA1244). None of these results were replicated. Candidate gene analysis supported the association of a polymorphism in NTRK2 with suicidality. |
Genome-wide association study |
| [28] | 2836 individuals with bipolar disorder | Associated SNP (rs300774) on 2p25 related to the ACP1 gene was marginally associated with suicide risk. | Genome-wide association study |
| [29] | 250 individuals with treatment resistant MDD | No association was found between genotyped SNPs in the COMT gene and suicide attempts and suicide risk. Significant association between suicide risk and non-responders to antidepressant treatment was found. | Candidate gene, genome-wide association study |
| [12] | 4047 individuals with MDD, recurrent MDD, and bipolar disorder | Suggestive significance for suicide attempt and Rs935194. Meta-analysis found SNPs with suggestive significance: rs17173608 (RARRES2), rs17387100 (PROM1), rs3781878 (NCAM1), rs17010519 (HK2), rs13049531 (RCAN1), rs9394433 (RNF8). Polygenic scores for MDD significantly predicted suicidal ideation, this was also found for suicide attempt in a validation dataset. |
Genome-wide association study, polygenic score analysis, meta-analysis. |
| [30] | 959 individuals with bipolar disorder | Associated genes with suicide severity were found at chromosome 8q12 (LINC000968/PENK), and at chromosome 10p11.2 (CCDC7/C10orf6/ITGB1) Suggestive genes associated with suicide attempt were found at 8q12-q21 (IL7) and at 18q22 (TMX3). |
Genome-wide association study, meta-analysis. |
| [31] | 475 individuals, suicide attempters and suicides 1133 controls, with MDD or healthy |
No association between suicidal behavior and CNV was found at genome-wide significant level. Highlighted results were CNVs at 6p22.2 including a H1 gene cluster and at 12q12 (LRRK2). |
Cases and controls, PCR. |
| [13] | 577 individuals, suicide attempters and suicides 1233 individuals, non-attempter psychiatric and healthy controls |
Comparing suicidal behavior (SB) to no SB, no SNPs reached genome wide significance, five SNPs had significant levels; rs11852984 (intergenic), rs6480463 (ADAMTS14), rs4575 (PSME2/RNF31), rs336284 (TBX20) and rs3019286 (STK3). Pathway analysis identified: “Cellular assembly and organization”, “nervous system development and function”, “cell death and survival”, “immunological disease”, “infectious disease” and “inflammatory response”. |
Genome-wide association study, pathway analysis |
| [32] | 660 individuals with severe suicide attempt 88 individuals with SCZ-related diagnoses 85 individuals with MDD 489 healthy individuals |
The top polygenes associated with neurodevelopment and suicide attempt were: CDH4, CDH12, CDH11, CDH13, CDH20, NRXN1, NRXN3, FGF12, NELL1, EPHB2, EPHA6, GLI2, MIXL1, MAML2, MS12, NTRK3, NPAS3, ODZ4, MYCBP2. Support evidence of a polygenic neurodevelopmental etiology in SB, also in absence of major psychiatric diagnoses. |
Genome-wide association study, polygenic risk scores |
| [11] | GWAS: 473 individuals, cases 9778 individuals, controls Including psychiatric disorders and suicide attempters Clinical case-control: 51 individuals, suicide attempters 112 controls |
Meta-analysis found significant association between suicide attempt and a locus on chromosome 6, near MRAP2 and CEP162, this consisted of 12 SNPs, peak SNP rs12524136-T, this was replicated in a meta-analysis of all studies and ancestral subgroups. Suggestive association was found for suicide attempt and bipolar disorder regarding the polygenic risk scores. |
Genome-wide association study, meta-analysis, cases and controls |
| [33] | 1780 individuals with schizophrenia 1768 healthy matched controls |
A 10 times higher mortality rate as well as high risk of multiple suicide attempts was replicated for persons with schizophrenia compared to the controls. No genetic overlap was found between PRS and mortality, or between PRS and multiple suicide attempts. Family history of mental disorders was found to be associated with higher mortality and multiple suicide attempts. | Cases and controls, polygenic risk scores |
| [9] | 6569 individuals with psychiatric disorders, all suicide attempters 17232 individuals with psychiatric disorders, all non-attempters |
Three significant loci were found: for MDD a SNP rs45593736 (an intron of the ARL5B), for BD an insertion-deletion polymorphism chr4_23273116_D (an intronic variant in the noncoding RNA LOC105374524). Polygenic risk scores for MDD were significantly associated with suicide attempt in MDD (R2 = 0.25%), BD (R2 = 0.24%) and schizophrenia (R2 = 0.40%). |
Genome-wide association study, polygenic risk scores |
| [34] | 6320 individuals with psychiatric disorders and SUD. | One genome-wide significant SNP s1677091 (LDHB). Other associations were rs683813 (ARNTL2), rs72740082 (FAH) and s11876255. Significant genetic overlap between MDD and suicide attempt severity was estimated up to 0.7% using PRS. |
Genome-wide association study, polygenic risk scores |
| [10] | 2433 individuals, all attempters, including psychiatric disorders 334766 controls 61676 individuals from electronic health records |
For suicide attempt significant heritability from common variation was estimated to 4%, and significant genetic correlation was found for depressive symptoms, neuroticism, MDD, schizophrenia and insomnia. For one sample two genomic regions with genome-wide significance were identified on chromosomes 5 and 19, the most significant SNPs being rs12972617 and rs12972618. | Genome-wide association study, polygenic risk scores, machine learning |
| [14] | 6024 individuals, all attempters, including psychiatric disorders 44240 controls, non-attempters, including psychiatric disorders |
Suggestive associations between SNPs, rs6880062 and rs6880461, and suicide attempt. Adjusted for mental disorders three significant associations were found on chromosome 20; rs4809706, rs4810824 and rs6019297. Heritability was found to be 4.6%, adjusted for mental disorders heritability was 1.9%. |
Genome-wide association study |