SUPPLEMENTARY MATERIAL

S1 - Literature Search Strategy

EMBASE Search Strategy (1980 – July 2011) – 216 results- 1 exp suicide/ or exp suicide gene/ or exp suicide attempt/- 2 (5HTR1A or 5HTR1B or 5HTR1D or 5HTR1E or 5HTR1F or 5HTR2A or 5HTR2C or

5HTR5A or 5HTR6 or ABCG1 or ADRA2A or APOE or BDNF or CCK or COMT or CRHR1 or DCP1 or DHCR7 or DRD2 or DRD4 or ESR1 or GABRA3 or GS3KB or HMGCR or LDLR or LPL or MAOA or NTRK2 or SCN8A or SLC6A4 or TPH or TH or VAMP4 or WFS1 or RGS2).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]

- 3 1 and 2

MEDLINE Search Strategy (1960 – July 2011) - 262 results- 1 exp Suicide/ or exp Genes, Transgenic, Suicide/ or exp Suicide, Attempted/- 2 (5HTR1A or 5HTR1B or 5HTR1D or 5HTR1E or 5HTR1F or 5HTR2A or 5HTR2C or

5HTR5A or 5HTR6 or ABCG1 or ADRA2A or APOE or BDNF or CCK or COMT or CRHR1 or DCP1 or DHCR7 or DRD2 or DRD4 or ESR1 or GABRA3 or GS3KB or HMGCR or LDLR or LPL or MAOA or NTRK2 or SCN8A or SLC6A4 or TPH or TH or VAMP4 or WFS1 or RGS2).mp. [mp=protocol supplementary concept, rare disease supplementary concept, title, original title, abstract, name of substance word, subject heading word, unique identifier]

- 3 1 and 2

PsycINFO Search Strategy (1806 – July 2011) – 40 results- 1exp Attempted Suicide/ or exp Suicide/- 2(5HTR1A or 5HTR1B or 5HTR1D or 5HTR1E or 5HTR1F or 5HTR2A or 5HTR2C or

5HTR5A or 5HTR6 or ABCG1 or ADRA2A or APOE or BDNF or CCK or COMT or CRHR1 or DCP1 or DHCR7 or DRD2 or DRD4 or ESR1 or GABRA3 or GS3KB or HMGCR or LDLR or LPL or MAOA or NTRK2 or SCN8A or SLC6A4 or TPH or TH or VAMP4 or WFS1 or RGS2).mp. [mp=title, abstract, heading word, table of contents, key concepts, original title, tests & measures]

- 3 1 and 2

PubMed Search Strategy (1950 – July 2011) – 19499 results- 1 Search 5HTR1A OR 5HTR1B OR 5HTR1D OR 5HTR1E OR 5HTR1F OR 5HTR2A

OR 5HTR2C OR 5HTR5A OR 5HTR6 OR ABCG1 OR ADRA2A OR apoe OR bdnf OR CCK OR comt OR CRHR1 OR DCP1 OR DHCR7 OR DRD2 OR DRD4 OR ESR1 OR GABRA3 OR GS3KB OR mgbr OR ldlr OR LPL OR maoa OR NTRK2 OR SCN8A OR SLC6A4 OR TPH OR TH OR VAMP4 OR WFS1 OR RGS2

- 2 Search suicide OR suicide attempt OR suicide ideation OR suicide completion OR suicidal

- 3 #1 AND #2

S2 – Modified Newcastle-Ottawa Rating Scale for Study Quality – Study characteristics and quality assessment of the ten most common genetic variants (with at least ten studies relating a genetic variant to suicidal behaviour) associated with suicidal behaviour using a modified Newcastle-Ottawa Rating Scale (studies with at least four stars are included in the meta-analyses) (n=112)

Author Year Design Selection of Controls

Definition of Controls

Age Above 18

Definition of Outcome

Ascertainment of Outcome

Study Quality

Abbar 2001 CC Y Y Y Y Y ******Akar 2010 CC Y Y Y Y Y ******Arango 2003 CC N N N N N *Arias 2001 CC Y Y Y Y Y ******Baca-Garcia 2002 CC Y Y ? Y Y *****Baca-Garcia 2004 CC Y Y Y N Y *****Baca-Garcia 2005 CC Y Y Y Y Y ******Bah 2008 CC N Y Y Y Y *****Baud 2007 CC Y Y Y Y Y ******Bayle 2003 CC Y Y Y N Y *****Bellivier 1998 CC Y Y Y Y Y ******Bellivier 2000 CC Y Y Y Y Y ******Bennett 2000 CC Y Y N Y Y *****Bondy 2000 CC Y Y Y N Y *****Campi-Azevedo 2003 CC Y Y ? Y Y *****Chen 2007 CC N Y Y Y Y *****Chong 2000 CC N Y Y Y Y *****Courtet 2001 CC Y Y Y Y Y ******Courtet 2003 CC Y Y Y Y Y ******Courtet 2004 CC N N Y Y Y ****Courtet 2005 CC Y Y Y Y Y ******Crawford 2000 CC Y Y ? Y Y *****De Lara 2006 CC N Y Y N Y ****De Luca 2005 NCC N N Y N Y **

De Luca 2006 NCC N N Y N Y **De Luca 2007 CC N N Y N Y ***De Luca (A) 2008 CC N Y Y Y Y *****De Luca (B) 2008 NCC N N Y N Y **Du 1999 CC Y Y Y N Y *****Du (A) 2000 CC Y Y Y Y Y ******Du (B) 2000 CC Y Y ? Y Y *****Du 2001 CC Y Y Y Y Y ******Ertugrul 2004 CC N Y Y N Y ****Fanous 2009 NCC N N ? Y Y **Fitch 2001 CC Y Y ? N Y ****Furlong 1998 NCC N N ? N Y *Geijer 2000 CC Y Y Y Y Y ******Gorwood 2000 CC Y Y Y N N ****Ho 2000 CC N Y Y Y Y *****Hong 2001 CC Y Y Y Y Y ******Hranilovic 2003 CC Y Y Y N Y *****Huang 1999 CC Y Y Y Y Y ******Huang 2003 CC Y Y Y Y Y ******Huang 2004 CC Y Y Y N Y *****Huang 2007 CC Y Y N Y Y *****Hwang 2006 CC Y Y Y N Y *****Jernej 2004 CC Y Y Y Y N *****Khait 2005 CC Y Y Y N Y *****Kirov 1999 CC N N Y N N **Koller 2005 CC N Y Y Y Y *****Kunugi 1999 CC Y Y Y N Y *****Lee 2010 CC Y Y Y Y Y ******Lemonde 2003 CC Y Y Y Y Y ******Limosin 2005 CC Y Y Y N Y *****Liu 2006 CC Y Y Y N Y *****Lung 2011 CC Y Y Y N Y *****Mann 2000 CC Y Y Y Y Y ******

Murphy 2011 CC Y Y Y Y Y ******Nedic 2010 CC Y Y Y N Y *****Neves 2008 CC Y Y ? Y Y *****New 2001 CC N Y Y Y Y *****Nielsen 1998 CC Y Y Y Y Y ******Nishigushi 2001 CC Y Y Y Y Y ******Nolan 2000 CC N Y Y Y Y *****Ohara 1998 CC N Y Y Y Y *****Ohtani 2004 CC Y N N N Y ***Ono 2000 CC Y N Y N Y ****Ono 2002 CC Y Y Y N Y *****Ono 2004 CC Y Y Y N Y *****Paik 2000 CC Y Y Y Y Y *****Pivac 2011 CC Y N Y N Y ****Pooley 2003 CC Y Y Y Y Y ******Preuss 2000 CC Y Y Y Y Y ******Preuss 2001 CC Y Y Y N Y *****Rujescu 2001 CC Y Y Y N Y *****Rujescu 2002 CC Y Y Y N Y *****Rujescu 2003 CC Y Y Y Y Y ******Russ 2000 CC N Y Y Y Y *****Saiz 2008 CC Y Y Y Y Y ******Saiz 2011 CC Y Y Y Y Y ******Segal 2006 CC Y Y Y Y Y *****Serretti 2007 CC Y Y Y Y Y ******Serretti 2009 CC Y Y Y Y Y ******Shen 2004 CC Y Y Y Y Y *****Souery 2001 CC Y Y ? Y Y *****Spalletta 2010 CC N N Y N N **Stefulj 2004 CC Y Y Y Y Y ******Stefulj 2005 CC Y Y Y Y Y *****Stefulj 2006 CC Y Y ? Y Y *****Tan 2002 CC N Y ? Y Y ****

Tsai (A) 1999 CC Y N Y Y Y ****Tsai (B) 1999 CC Y Y Y N Y *****Turecki 1999 CC Y Y Y N Y *****Turecki 2001 CC Y Y Y Y Y ******Turecki 2003 CC Y Y ? Y Y *****Vaquero-Lorenzo 2008 CC Y N Y Y Y *****Viana 2006 CC N Y Y Y Y *****Videtic 2009 CC N Y Y Y N ****Vincze 2008 CC Y Y Y Y Y *****Wang 2009 N N N Y Y Y ***Wasserman 2006 N N N Y Y Y ***Yoon 2008 CC Y Y Y Y Y ******Yoon 2009 CC Y Y Y Y Y ******Zai 2011 CC N N ? N Y **Zalsman 2001 CC Y Y N Y Y *****Zalsman 2005 NCC Y Y N Y Y ****Zalsman 2006 CC Y Y Y N Y *****Zalsman 2008 CC Y Y Y Y Y ******Zalsman 2011 CC Y N N Y Y ****Zhang 1997 CC Y Y Y Y Y ******Zhang 2008 CC N Y Y N Y ****Zouk 2007 CC Y Y Y Y Y ******

1. Abbar M, Courtet P, Bellivier F, Leboyer M, Boulenger JP, Castelhau D, et al. Suicide attempts and the tryptophan hydroxylase gene. Molecular psychiatry. 2001;6(3):268-73.2. Akar T, Sayin A, Bakkaloglu Z, Cabuk DK, Kucukyildirim S, Demirel B, et al. Investigation of serotonin transporter gene promoter (5-HTTLPR) and intron 2 (variable number of tandem repeats) polymorphisms with suicidal behavior in a Turkish population. DNA Cell Biol. 2010;29(8):429-34.3. Arango V, Huang Y-y, Underwood MD, Mann JJ. Genetics of the serotonergic system in suicidal behavior. Journal of psychiatric research. 2003;37(5):375-86.

4. Arias B, Gastó C, Catalán R, Gutiérrez B, Pintor L, Fañanás L. The 5-HT2A receptor gene 102T/C polymorphism is associated with suicidal behavior in depressed patients. American journal of medical genetics. 2001;105(8):801-4.5. Baca-Garcia E, Vaquero C, Diaz-Sastre C, Saiz-Ruiz J, Fernandez-Piqueras J, de Leon J. A gender-specific association between the serotonin transporter gene and suicide attempts. Neuropsychopharmacology. 2002;26(5):692-5.6. Baca-Garcia E, Vaquero C, Diaz-Sastre C, Garcia-Resa E, Saiz-Ruiz J, Fernandez-Piqueras J, et al. Lack of association between the serotonin transporter promoter gene polymorphism and impulsivity or aggressive behavior among suicide attempters and healthy volunteers. Psychiatry Res. 2004;126(2):99-106.7. Baca-Garcia E, Salgado BR, Segal HD, Lorenzo CV, Acosta MN, Romero MA, et al. A pilot genetic study of the continuum between compulsivity and impulsivity in females: the serotonin transporter promoter polymorphism. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(5):713-7.8. Bah J, Lindstrom M, Westberg L, Manneras L, Ryding E, Henningsson S, et al. Serotonin transporter gene polymorphisms: effect on serotonin transporter availability in the brain of suicide attempters. Psychiatry Res. 2008;162(3):221-9.9. Baud P, Courtet P, Perroud N, Jollant F, Buresi C, Malafosse A. Catechol-O-methyltransferase polymorphism (COMT) in suicide attempters: a possible gender effect on anger traits. American journal of medical genetics Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2007;144B(8):1042-7. Epub 2007/05/19.10. Bayle FJ, Leroy S, Gourion D, Millet B, Olie JP, Poirier MF, et al. 5HTTLPR polymorphism in schizophrenic patients: further support for association with violent suicide attempts. Am J Med Genet B Neuropsychiatr Genet. 2003;119B(1):13-7.11. Bellivier F, Leboyer M, Courtet P, Buresi C, Beaufils B, Samolyk D, et al. Association between the tryptophan hydroxylase gene and manic-depressive illness. Arch Gen Psychiatry. 1998;55(1):33-7.12. Bellivier F, Szoke A, Henry C, Lacoste J, Bottos C, Nosten-Bertrand M, et al. Possible association between serotonin transporter gene polymorphism and violent suicidal behavior in mood disorders. Biol Psychiatry. 2000;48(4):319-22.13. Bennett PJ, McMahon WM, Watabe J, Achilles J, Bacon M, Coon H, et al. Tryptophan hydroxylase polymorphisms in suicide victims. Psychiatr Genet. 2000;10(1):13-7.14. Bondy B, Kuznik J, Baghai T, Schule C, Zwanzger P, Minov C, et al. Lack of association of serotonin-2A receptor gene polymorphism (T102C) with suicidal ideation and suicide. Am J Med Genet. 2000;96(6):831-5.15. Campi-Azevedo AC, Boson W, De Marco L, Romano-Silva MA, Correa H. Association of the serotonin transporter promoter polymorphism with suicidal behavior. Mol Psychiatry. 2003;8(11):899-900.16. Chen CK, Lin SK, Huang MC, Su LW, Hsiao CC, Chiang YL, et al. Analysis of association of clinical correlates and 5-HTTLPR polymorphism with suicidal behavior among Chinese methamphetamine abusers. Psychiatry Clin Neurosci. 2007;61(5):479-86.17. Chong SA, Lee WL, Tan CH, Tay AH, Chan AO, Tan EC. Attempted suicide and polymorphism of the serotonin transporter gene in Chinese patients with schizophrenia. Psychiatry Res. 2000;97(2-3):101-6.18. Courtet P, Baud P, Abbar M, Boulenger JP, Castelnau D, Mouthon D, et al. Association between violent suicidal behavior and the low activity allele of the serotonin transporter gene. Mol Psychiatry. 2001;6(3):338-41.

19. Courtet P, Buresi C, Abbar M, Baud P, Boulenger JP, Castelnau D, et al. No association between non-violent suicidal behavior and the serotonin transporter promoter polymorphism. Am J Med Genet B Neuropsychiatr Genet. 2003;116B(1):72-6.20. Courtet P, Picot MC, Bellivier F, Torres S, Jollant F, Michelon C, et al. Serotonin transporter gene may be involved in short-term risk of subsequent suicide attempts. Biol Psychiatry. 2004;55(1):46-51.21. Courtet P, Jollant F, Buresi C, Castelnau D, Mouthon D, Malafosse A. The monoamine oxidase A gene may influence the means used in suicide attempts. Psychiatr Genet. 2005;15(3):189-93.22. Crawford J, Sutherland GR, Goldney RD. No evidence for association of 5-HT2A receptor polymorphism with suicide. Am J Med Genet. 2000;96(6):879-80.23. Lopez de Lara C, Dumais A, Rouleau G, Lesage A, Dumont M, Chawky N, et al. STin2 variant and family history of suicide as significant predictors of suicide completion in major depression. Biol Psychiatry. 2006;59(2):114-20. Epub 2005 Aug 25.24. De Luca V, Tharmalingam S, Sicard T, Kennedy JL. Gene-gene interaction between MAOA and COMT in suicidal behavior. Neurosci Lett. 2005;383(1-2):151-4. Epub 2005/06/07.25. De Luca V, Tharmalingam S, Muller DJ, Wong G, de Bartolomeis A, Kennedy JL. Gene-gene interaction between MAOA and COMT in suicidal behavior: analysis in schizophrenia. Brain research. 2006;1097(1):26-30. Epub 2006/05/27.26. De Luca V, Likhodi O, Kennedy JL, Wong AH. Differential expression and parent-of-origin effect of the 5-HT2A receptor gene C102T polymorphism: analysis of suicidality in schizophrenia and bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2007;144B(3):370-4.27. De Luca V, Tharmaligam S, Strauss J, Kennedy JL. 5-HT2C receptor and MAO-A interaction analysis: no association with suicidal behaviour in bipolar patients. European archives of psychiatry and clinical neuroscience. 2008;258(7):428-33. Epub 2008/05/28.28. De Luca V, Strauss J, Kennedy JL. Power based association analysis (PBAT) of serotonergic and noradrenergic polymorphisms in bipolar patients with suicidal behaviour. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(1):197-203. Epub 2007 Aug 19.29. Du L, Faludi G, Palkovits M, Demeter E, Bakish D, Lapierre YD, et al. Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims. Biol Psychiatry. 1999;46(2):196-201.30. Du L, Bakish D, Lapierre YD, Ravindran AV, Hrdina PD. Association of polymorphism of serotonin 2A receptor gene with suicidal ideation in major depressive disorder. Am J Med Genet. 2000;96(1):56-60.31. Du L, Faludi G, Palkovits M, Bakish D, Hrdina PD. Tryptophan hydroxylase gene 218A/C polymorphism is not associated with depressed suicide. Int J Neuropsychopharmacol. 2000;3(3):215-20.32. Du L, Bakish D, Hrdina PD. Tryptophan hydroxylase gene 218A/C polymorphism is associated with somatic anxiety in major depressive disorder. J Affect Disord. 2001;65(1):37-44.33. Ertugrul A, Kennedy JL, Masellis M, Basile VS, Jayathilake K, Meltzer HY. No association of the T102C polymorphism of the serotonin 2A receptor gene (HTR2A) with suicidality in schizophrenia. Schizophr Res. 2004;69(2-3):301-5.34. Fanous AH, Chen X, Wang X, Amdur R, O'Neill FA, Walsh D, et al. Genetic variation in the serotonin 2A receptor and suicidal ideation in a sample of 270 Irish high-density schizophrenia families. Am J Med Genet B Neuropsychiatr Genet. 2009;150B(3):411-7.35. Fitch D, Lesage A, Seguin M, Trousignant M, Bankelfat C, Rouleau GA, et al. Suicide and the serotonin transporter gene. Mol Psychiatry. 2001;6(2):127-8.

36. Furlong RA, Ho L, Rubinsztein JS, Walsh C, Paykel ES, Rubinsztein DC. No association of the tryptophan hydroxylase gene with bipolar affective disorder, unipolar affective disorder, or suicidal behaviour in major affective disorder. Am J Med Genet. 1998;81(3):245-7.37. Geijer T, Frisch A, Persson ML, Wasserman D, Rockah R, Michaelovsky E, et al. Search for association between suicide attempt and serotonergic polymorphisms. Psychiatr Genet. 2000;10(1):19-26.38. Gorwood P, Batel P, Ades J, Hamon M, Boni C. Serotonin transporter gene polymorphisms, alcoholism, and suicidal behavior. Biol Psychiatry. 2000;48(4):259-64.39. Ho LW, Furlong RA, Rubinsztein JS, Walsh C, Paykel ES, Rubinsztein DC. Genetic associations with clinical characteristics in bipolar affective disorder and recurrent unipolar depressive disorder. Am J Med Genet. 2000;96(1):36-42.40. Hong CJ, Tsai, S.J., Wang, Y.C. Association between tryptophan hydroyxlase gene polymorphism (A218C) and schizophrenic disorders. Schizophr Res. 2001;49:59-63.41. Hranilovic D, Stefulj J, Furac I, Kubat M, Balija M, Jernej B. Serotonin transporter gene promoter (5-HTTLPR) and intron 2 (VNTR) polymorphisms in Croatian suicide victims. Biol Psychiatry. 2003;54(9):884-9.42. Huang YY, Grailhe R, Arango V, Hen R, Mann JJ. Relationship of psychopathology to the human serotonin1B genotype and receptor binding kinetics in postmortem brain tissue. Neuropsychopharmacology. 1999;21(2):238-46.43. Huang YY, Oquendo MA, Friedman JM, Greenhill LL, Brodsky B, Malone KM, et al. Substance abuse disorder and major depression are associated with the human 5-HT1B receptor gene (HTR1B) G861C polymorphism. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2003;28(1):163-9. Epub 2002/12/24.44. Huang YY, Battistuzzi C, Oquendo MA, Harkavy-Friedman J, Greenhill L, Zalsman G, et al. Human 5-HT1A receptor C(-1019)G polymorphism and psychopathology. Int J Neuropsychopharmacol. 2004;7(4):441-51. Epub 2004/10/08.45. Huang TL, Lee, C.T. Associations between BDNF G196A gene polymorphism and clinical phenotypes in schizophrenia patients. Chang Gung Med J. 2007;30(5):408-12.46. Hwang JP, Tsai SJ, Hong CJ, Yang CH, Lirng JF, Yang YM. The Val66Met polymorphism of the brain-derived neurotrophic-factor gene is associated with geriatric depression. Neurobiology of aging. 2006;27(12):1834-7. Epub 2005/12/14.47. Jernej B, Stefulj J, Hranilovic D, Balija M, Skavic J, Kubat M. Intronic polymorphism of tryptophan hydroxylase and serotonin transporter: indication for combined effect in predisposition to suicide. J Neural Transm. 2004;111(6):733-8. Epub 2004/05/29.48. Khait VD, Huang YY, Zalsman G, Oquendo MA, Brent DA, Harkavy-Friedman JM, et al. Association of serotonin 5-HT2A receptor binding and the T102C polymorphism in depressed and healthy Caucasian subjects. Neuropsychopharmacology. 2005;30(1):166-72.49. Kirov G, Owen MJ, Jones I, McCandless F, Craddock N. Tryptophan Hydroxylase Gene and Manic-Depressive Illness. Arch Gen Psychiatry. 1999;56(1):98-9.50. Koller G, Engel RR, Preuss UW, Karakesisoglou A, Zill P, Bondy B, et al. Tryptophan hydroxylase gene 1 polymorphisms are not associated with suicide attempts in alcohol-dependent individuals. Addict Biol. 2005;10(3):269-73.51. Kunugi H, Ishida S, Kato T, Tatsumi M, Sakai T, Hattori M, et al. A functional polymorphism in the promoter region of monoamine oxidase-A gene and mood disorders. Mol Psychiatry. 1999;4(4):393-5.

52. Lee HY, Kim YK. Gender effect of catechol-O-methyltransferase Val158Met polymorphism on suicidal behavior. Neuropsychobiology. 2011;63(3):177-82. Epub 2011 Feb 8.53. Lemonde S, Du L, Bakish D, Hrdina P, Albert PR. Association of the C(-1019)G 5-HT1A functional promoter polymorphism with antidepressant response. Int J Neuropsychopharmacol. 2004;7(4):501-6. Epub 2004/09/28.54. Limosin F, Loze JY, Boni C, Hamon M, Ades J, Rouillon F, et al. Male-specific association between the 5-HTTLPR S allele and suicide attempts in alcohol-dependent subjects. J Psychiatr Res. 2005;39(2):179-82.55. Liu X, Li H, Qin W, He G, Li D, Shen Y, et al. Association of TPH1 with suicidal behaviour and psychiatric disorders in the Chinese population. Journal of medical genetics. 2006;43(2):e4. Epub 2006/02/10.56. Lung FW, Tzeng DS, Huang MF, Lee MB. Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder. BMC medical genetics. 2011;12:74. Epub 2011/05/25.57. Mann JJ, Huang YY, Underwood MD, Kassir SA, Oppenheim S, Kelly TM, et al. A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Arch Gen Psychiatry. 2000;57(8):729-38.58. Murphy TM, Ryan M, Foster T, Kelly C, McClelland R, O'Grady J, et al. Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms. Behavioral and brain functions : BBF. 2011;7:22. Epub 2011/06/30.59. Nedic G, Nikolac M, Sviglin KN, Muck-Seler D, Borovecki F, Pivac N. Association study of a functional catechol-O-methyltransferase (COMT) Val108/158Met polymorphism and suicide attempts in patients with alcohol dependence. Int J Neuropsychopharmacol. 2011;14(3):377-88. Epub 2010 Sep 22.60. Neves FS, Silveira G, Romano-Silva MA, Malloy-Diniz L, Ferreira AA, De Marco L, et al. Is the 5-HTTLPR polymorphism associated with bipolar disorder or with suicidal behavior of bipolar disorder patients? American journal of medical genetics Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2008;147B(1):114-6. Epub 2007/06/21.61. New AS, Gelernter J, Goodman M, Mitropoulou V, Koenigsberg H, Silverman J, et al. Suicide, impulsive aggression, and HTR1B genotype. Biol Psychiatry. 2001;50(1):62-5.62. Nielsen DA, Virkkunen, M., Lappalainen, J., Eggert, M., Brown, G.L., Long, J.C., Goldman, D., Linnoila, M. A TPH gene marker for suicidality and alcoholism. Arch Gen Psychiatry. 1998;55:593-602.63. Nishiguchi N, Shirakawa O, Ono H, Nishimura A, Nushida H, Ueno Y, et al. Lack of an association between 5-HT1A receptor gene structural polymorphisms and suicide victims. American journal of medical genetics. 2002;114(4):423-5. Epub 2002/05/07.64. Nolan KA, Volavka J, Czobor P, Cseh A, Lachman H, Saito T, et al. Suicidal behavior in patients with schizophrenia is related to COMT polymorphism. Psychiatr Genet. 2000;10(3):117-24.65. Ohara K, Nagai M, Tsukamoto T, Tani K, Suzuki Y. 5-HT2A receptor gene promoter polymorphism--1438G/A and mood disorders. Neuroreport. 1998;9(6):1139-41.66. Ohtani M, Shindo S, Yoshioka N. Polymorphisms of the tryptophan hydroxylase gene and serotonin 1A receptor gene in suicide victims among Japanese. Tohoku J Exp Med. 2004;202(2):123-33.

67. Ono H, Shirakawa, O., Nishiguchi, N., Nishimura, A., Nushida, H., Ueno, Y., Maeda, K. Tryptophan hydroxylase Gene polymorphisms are not associated with suicide. American journal of medical genetics Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2000;96(861-863).68. Ono H, Shirakawa O, Nishiguchi N, Nishimura A, Nushida H, Ueno Y, et al. No evidence of an association between a functional monoamine oxidase a gene polymorphism and completed suicides. Am J Med Genet. 2002;114(3):340-2.69. Ono H, Shirakawa O, Nushida H, Ueno Y, Maeda K. Association between catechol-O-methyltransferase functional polymorphism and male suicide completers. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2004;29(7):1374-7. Epub 2004/05/06.70. Paik I, Toh K, Kim J, Lee C. TPH gene may be associated with suicidal behavior, but not with schizophrenia in the Korean population. Hum Hered. 2000;50(6):365-9.71. Pivac N, Pregelj P, Nikolac M, Zupanc T, Nedic G, Muck Seler D, et al. The association between catechol-O-methyl-transferase Val108/158Met polymorphism and suicide. Genes Brain Behav. 2011;10(5):565-9. doi: 10.1111/j.601-183X.2011.00695.x. Epub 2011 May 3.72. Pooley EC, Houston K, Hawton K, Harrison PJ. Deliberate self-harm is associated with allelic variation in the tryptophan hydroxylase gene (TPH A779C), but not with polymorphisms in five other serotonergic genes. Psychological Medicine. 2003;33(5):775-83.73. Preuss UW, Koller G, Bahlmann M, Soyka M, Bondy B. No association between suicidal behavior and 5-HT2A-T102C polymorphism in alcohol dependents. Am J Med Genet. 2000;96(6):877-8.74. Preuss UW, Koller G, Soyka M, Bondy B. Association between suicide attempts and 5-HTTLPR-S-allele in alcohol-dependent and control subjects: further evidence from a German alcohol-dependent inpatient sample. Biol Psychiatry. 2001;50(8):636-9.75. Rujescu D, Giegling I, Sato T, Moeller HJ. A polymorphism in the promoter of the serotonin transporter gene is not associated with suicidal behavior. Psychiatr Genet. 2001;11(3):169-72.76. Rujescu D, Giegling I, Bondy B, Gietl A, Zill P, Moller HJ. Association of anger-related traits with SNPs in the TPH gene. Mol Psychiatry. 2002;7(9):1023-9.77. Rujescu D, Giegling I, Sato T, Moller HJ. Lack of association between serotonin 5-HT1B receptor gene polymorphism and suicidal behavior. American journal of medical genetics Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2003;116B(1):69-71. Epub 2002/12/24.78. Russ MJ, Lachman HM, Kashdan T, Saito T, Bajmakovic-Kacila S. Analysis of catechol-O-methyltransferase and 5-hydroxytryptamine transporter polymorphisms in patients at risk for suicide. Psychiatry Res. 2000;93(1):73-8.79. Saiz PA, Garcia-Portilla MP, Paredes B, Arango C, Morales B, Alvarez V, et al. Association between the A-1438G polymorphism of the serotonin 2A receptor gene and nonimpulsive suicide attempts. Psychiatr Genet. 2008;18(5):213-8.80. Saiz PA, Garcia-Portilla P, Paredes B, Corcoran P, Arango C, Morales B, et al. Role of serotonergic-related systems in suicidal behavior: Data from a case-control association study. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(6):1518-24. Epub 2011 May 7.81. Segal J, Pujol C, Birck A, Gus Manfro G, Leistner-Segal S. Association between suicide attempts in south Brazilian depressed patients with the serotonin transporter polymorphism. Psychiatry Res. 2006;143(2-3):289-91. Epub 2006 Jul 21.

82. Serretti A, Mandelli L, Giegling I, Schneider B, Hartmann AM, Schnabel A, et al. HTR2C and HTR1A gene variants in German and Italian suicide attempters and completers. American journal of medical genetics Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2007;144B(3):291-9. Epub 2006/12/29.83. Serretti A, Calati R, Giegling I, Hartmann AM, Moller HJ, Rujescu D. Serotonin receptor HTR1A and HTR2C variants and personality traits in suicide attempters and controls. Journal of psychiatric research. 2009;43(5):519-25. Epub 2008/08/22.84. Shen Y, Li H, Gu N, Tan Z, Tang J, Fan J, et al. Relationship between suicidal behavior of psychotic inpatients and serotonin transporter gene in Han Chinese. Neurosci Lett. 2004;372(1-2):94-8.85. Souery D, Van Gestel S, Massat I, Blairy S, Adolfsson R, Blackwood D, et al. Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders: a multicenter association study. Biol Psychiatry. 2001;49(5):405-9.86. Spalletta G, Morris DW, Angelucci F, Rubino IA, Spoletini I, Bria P, et al. BDNF Val66Met polymorphism is associated with aggressive behavior in schizophrenia. European psychiatry : the journal of the Association of European Psychiatrists. 2010;25(6):311-3. Epub 2010/05/01.87. Stefulj J, Buttner A, Kubat M, Zill P, Balija M, Eisenmenger W, et al. 5HT-2C receptor polymorphism in suicide victims. Association studies in German and Slavic populations. European archives of psychiatry and clinical neuroscience. 2004;254(4):224-7. Epub 2004/08/17.88. Stefulj J, Kubat M, Balija M, Skavic J, Jernej B. Variability of the tryptophan hydroxylase gene: study in victims of violent suicide. Psychiatry Res. 2005;134(1):67-73.89. Stefulj J, Kubat M, Balija M, Jernej B. TPH gene polymorphism and aging: indication of combined effect on the predisposition to violent suicide. Am J Med Genet B Neuropsychiatr Genet. 2006;141B(2):139-41.90. Tan EC, Chong SA, Chan AO, Tan CH. No evidence for association of the T102C polymorphism in the serotonin type 2A receptor with suicidal behavior in schizophrenia. Am J Med Genet. 2002;114(3):321-2.91. Tsai SJ, Hong CJ, Wang YC. Tryptophan hydroxylase gene polymorphism (A218C) and suicidal behaviors. Neuroreport. 1999;10(18):3773-5.92. Tsai SJ, Hong CJ, Hsu CC, Cheng CY, Liao WY, Song HL, et al. Serotonin-2A receptor polymorphism (102T/C) in mood disorders. Psychiatry Res. 1999;87(2-3):233-7.93. Turecki G, Briere R, Dewar K, Antonetti T, Lesage AD, Seguin M, et al. Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am J Psychiatry. 1999;156(9):1456-8.94. Turecki G. Suicidal behavior: is there a genetic predisposition? Bipolar Disord. 2001;3(6):335-49.95. Turecki G, Sequeira A, Gingras Y, Seguin M, Lesage A, Tousignant M, et al. Suicide and serotonin: study of variation at seven serotonin receptor genes in suicide completers. American journal of medical genetics Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2003;118B(1):36-40. Epub 2003/03/11.96. Vaquero-Lorenzo C, Baca-Garcia E, Diaz-Hernandez M, Perez-Rodriguez MM, Fernandez-Navarro P, Giner L, et al. Association study of two polymorphisms of the serotonin-2A receptor gene and suicide attempts. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(5):645-9.

97. Viana MM, De Marco LA, Boson WL, Romano-Silva MA, Correa H. Investigation of A218C tryptophan hydroxylase polymorphism: association with familial suicide behavior and proband's suicide attempt characteristics. Genes, brain, and behavior. 2006;5(4):340-5. Epub 2006/05/24.98. Videtic A, Peternelj TT, Zupanc T, Balazic J, Komel R. Promoter and functional polymorphisms of HTR2C and suicide victims. Genes, brain, and behavior. 2009;8(5):541-5. Epub 2009/06/06.99. Vincze I, Perroud N, Buresi C, Baud P, Bellivier F, Etain B, et al. Association between brain-derived neurotrophic factor gene and a severe form of bipolar disorder, but no interaction with the serotonin transporter gene. Bipolar Disord. 2008;10(5):580-7.100. Wang S, Zhang K, Xu Y, Sun N, Shen Y, Xu Q. An association study of the serotonin transporter and receptor genes with the suicidal ideation of major depression in a Chinese Han population. Psychiatry research. 2009;170(2-3):204-7. Epub 2009/11/10.101. Wasserman D, Geijer T, Sokolowski M, Rozanov V, Wasserman J. The serotonin 1A receptor C(-1019)G polymorphism in relation to suicide attempt. Behavioral and brain functions : BBF. 2006;2:14. Epub 2006/04/22.102. Yoon HK, Kim YK. Association between serotonin-related gene polymorphisms and suicidal behavior in depressive patients. Progress in neuro-psychopharmacology & biological psychiatry. 2008;32(5):1293-7. Epub 2008/05/27.103. Yoon HK, Kim YK. TPH2 -703G/T SNP may have important effect on susceptibility to suicidal behavior in major depression. Progress in neuro-psychopharmacology & biological psychiatry. 2009;33(3):403-9. Epub 2009/01/24.104. Zai CC, Manchia M, De Luca V, Tiwari AK, Chowdhury NI, Zai GC, et al. The brain-derived neurotrophic factor gene in suicidal behaviour: a meta-analysis. Int J Neuropsychopharmacol. 2011:1-6. Epub 2011/08/31.105. Zalsman G, Frisch A, King RA, Pauls DL, Grice DE, Gelernter J, et al. Case control and family-based studies of tryptophan hydroxylase gene A218C polymorphism and suicidality in adolescents. Am J Med Genet. 2001;105(5):451-7.106. Zalsman G, Anderson GM, Peskin M, Frisch A, King RA, Vekslerchik M, et al. Relationships between serotonin transporter promoter polymorphism, platelet serotonin transporter binding and clinical phenotype in suicidal and non-suicidal adolescent inpatients. J Neural Transm. 2005;112(2):309-15.107. Zalsman G, Huang YY, Oquendo MA, Burke AK, Hu XZ, Brent DA, et al. Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression. Am J Psychiatry. 2006;163(9):1588-93.108. Zalsman G, Huang YY, Oquendo MA, Brent DA, Giner L, Haghighi F, et al. No association of COMT Val158Met polymorphism with suicidal behavior or CSF monoamine metabolites in mood disorders. Archives of suicide research : official journal of the International Academy for Suicide Research. 2008;12(4):327-35. Epub 2008/10/02.109. Zalsman G, Patya M, Frisch A, Ofek H, Schapir L, Blum I, et al. Association of polymorphisms of the serotonergic pathways with clinical traits of impulsive-aggression and suicidality in adolescents: a multi-center study. World J Biol Psychiatry. 2011;12(1):33-41. Epub 2010 Sep 27.110. Zhang HY, Ishigaki T, Tani K, Chen K, Shih JC, Miyasato K, et al. Serotonin2A receptor gene polymorphism in mood disorders. Biol Psychiatry. 1997;41(7):768-73.111. Zhang J, Shen Y, He G, Li X, Meng J, Guo S, et al. Lack of association between three serotonin genes and suicidal behavior in Chinese psychiatric patients. Progress in neuro-psychopharmacology & biological psychiatry. 2008;32(2):467-71. Epub 2007/10/30.

112. Zouk H, McGirr A, Lebel V, Benkelfat C, Rouleau G, Turecki G. The effect of genetic variation of the serotonin 1B receptor gene on impulsive aggressive behavior and suicide. American journal of medical genetics Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2007;144B(8):996-1002. Epub 2007/05/19.

S3 – Plots of Square root (Sample Size) versus Precision for SLC6A4 Polymorphism (A) and TPH rs1800532 (B)– These plots were used to identify significant variation in studies that may have existed after meeting inclusion criteria. Studies greater than two standard deviations from the trendline were excluded from the pooled effect estimate (number of studies excluded=0) due to the fact that they may have significant influence on the accuracy of pooled results.