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Family-based study of HTR2A in suicide attempts: observed gene, gene × environment and parent-of-origin associations

Molecular Psychiatry volume 18, pages 758–766 (2013)Cite this article

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Abstract

While suicidal behavior is frequently accompanied by serotonergic system alterations, specific associations with genetic variation in the serotonin 2A receptor (HTR2A) gene have been inconsistent. Using a family-based study design of 660 offspring who have made a suicide attempt (SA) and both parents, we conducted an association and linkage analysis using single-nucleotide polymorphisms (SNPs) with extensive gene coverage, and included the study of parent-of-origin (POE) and gene–environment interaction (G × E), also using previously unstudied exposures. The main finding was a G × E between the exon 1 SNP rs6313 and exposure to cumulative types of lifetime stressful life events (SLEs), driven by overtransmission of CT and undertransmission of TT, both in relation to other genotypes. Further exploratory analysis revealed a significant POE in this G × E in female subjects, which followed a polar overdominant inheritance pattern. In addition, rs6310 and rs6305 were found to significantly associate with SA in the total sample. A G × E in female subjects (rs7322347 × physical assault in childhood/adolescence) confirmed features of a previously observed association with SA. Other potentially interesting nominally significant findings were observed, but like the G × E of rs7322347 did not pass a false-discovery rate cutoff. Taken together, this study found multiple associations of HTR2A SNPs on SA, with strongest statistical evidence for a G × E involving rs6313, and further suggested the importance of taking into account different inheritance patterns and G × Es with regard to HTR2A.

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References

  1. World Health Organization. Suicide prevention (SUPRE) global statistics http://www.who.int/mental_health/prevention/suicide/. (accessed date 2002).

  2. Bertolote JM, Fleischmann A, De Leo D, Wasserman D . Suicidal thoughts, suicide plans and attempts in the general population on different continents. In: Wasserman D, Wasserman C (eds). Oxford Textbook of Suicidology and Suicide Prevention. Oxford University Press: Oxford, UK, 2009, pp 99–104.

    Google Scholar 

  3. Gottesman II, Gould TD . The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003; 160: 636–645.

    Article  PubMed  Google Scholar 

  4. Lander ES, Schork NJ . Genetic dissection of complex traits. Science 1994; 265: 2037–2048.

    Article  CAS  PubMed  Google Scholar 

  5. Mann JJ, Arango VA, Avenevoli S, Brent DA, Champagne FA, Clayton P et al. Candidate endophenotypes for genetic studies of suicidal behavior. Biol Psychiatry 2009; 65: 556–563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Asberg M, Traskman L, Thoren P . 5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? Arch Gen Psychiatry 1976; 33: 1193–1197.

    Article  CAS  PubMed  Google Scholar 

  7. Mann JJ, Currier D . A review of prospective studies of biologic predictors of suicidal behavior in mood disorders. Arch Suicide Res Off J Int Acad Suicide Res 2007; 11: 3–16.

    Article  Google Scholar 

  8. Shaw DM, Camps FE, Eccleston EG . 5-Hydroxytryptamine in the hind-brain of depressive suicides. Br J Psychiatry 1967; 113: 1407–1411.

    Article  CAS  PubMed  Google Scholar 

  9. Stanley M, Virgilio J, Gershon S . Tritiated imipramine binding sites are decreased in the frontal cortex of suicides. Science 1982; 216: 1337–1339.

    Article  CAS  PubMed  Google Scholar 

  10. Audenaert K, Van Laere K, Dumont F, Slegers G, Mertens J, van Heeringen C et al. Decreased frontal serotonin 5-HT 2a receptor binding index in deliberate self-harm patients. Eur J Nucl Med 2001; 28: 175–182.

    Article  CAS  PubMed  Google Scholar 

  11. Stanley M, Mann JJ . Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet 1983; 1: 214–216.

    Article  CAS  PubMed  Google Scholar 

  12. Stockmeier CA . Involvement of serotonin in depression: evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. J Psychiatr Res 2003; 37: 357–373.

    Article  PubMed  Google Scholar 

  13. Serretti A, Drago A, De Ronchi D . HTR2A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies. Curr Med Chem 2007; 14: 2053–2069.

    Article  CAS  PubMed  Google Scholar 

  14. Norton N, Owen MJ . HTR2A: association and expression studies in neuropsychiatric genetics. Ann Med 2005; 37: 121–129.

    Article  CAS  PubMed  Google Scholar 

  15. Anguelova M, Benkelfat C, Turecki G . A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: II. Suicidal behavior. Mol Psychiatry 2003; 8: 646–653.

    Article  CAS  PubMed  Google Scholar 

  16. Li D, Duan Y, He L . Association study of serotonin 2A receptor (5-HT2A) gene with schizophrenia and suicidal behavior using systematic meta-analysis. Biochem Biophys Res Commun 2006; 340: 1006–1015.

    Article  CAS  PubMed  Google Scholar 

  17. Brezo J, Bureau A, Mérette C, Jomphe V, Barker ED, Vitaro F et al. Differences and similarities in the serotonergic diathesis for suicide attempts and mood disorders: a 22-year longitudinal gene–environment study. Mol Psychiatry 2010; 15: 831–843.

    Article  CAS  PubMed  Google Scholar 

  18. Myers RL, Airey DC, Manier DH, Shelton RC, Sanders-Bush E . Polymorphisms in the regulatory region of the human serotonin 5-HT2A receptor gene (HTR2A) influence gene expression. Biol Psychiatry 2007; 61: 167–173.

    Article  CAS  PubMed  Google Scholar 

  19. Mann JJ, Waternaux C, Haas GL, Malone KM . Toward a clinical model of suicidal behavior in psychiatric patients. Am J Psychiatry 1999; 156: 181–189.

    CAS  PubMed  Google Scholar 

  20. Brodsky BS, Stanley B . Adverse childhood experiences and suicidal behavior. Psychiatric Clin N Am 2008; 31: 223–235.

    Article  Google Scholar 

  21. McEwen BS . Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev 2007; 87: 873–904.

    Article  PubMed  Google Scholar 

  22. 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 2007; 144B: 370–374.

    Article  CAS  Google Scholar 

  23. De Luca V, Viggiano E, Dhoot R, Kennedy JL, Wong AH . Methylation and QTDT analysis of the 5-HT2A receptor 102C allele: analysis of suicidality in major psychosis. J Psychiatr Res 2009; 43: 532–537.

    Article  PubMed  Google Scholar 

  24. Oades RD, Lasky-Su J, Christiansen H, Faraone SV, Sonuga-Barke EJ, Banaschewski T et al. The influence of serotonin and other genes on impulsive behavioral aggression and cognitive impulsivity in children with attention-deficit/hyperactivity disorder (ADHD): findings from a family-based association test (FBAT) analysis. Behav Brain Funct 2008; 4: 48.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Shaikh SA, Strauss J, King N, Bulgin NL, Vetro A, Kiss E et al. Association study of serotonin system genes in childhood-onset mood disorder. Psychiatr Genet 2008; 18: 47–52.

    Article  PubMed  Google Scholar 

  26. van Beijsterveldt CE, Middeldorp CM, Slof-Op’t Landt MC, Bartels M, Hottenga JJ, Suchiman HE et al. Influence of candidate genes on attention problems in children: a longitudinal study. Behav Genet 2011; 41: 155–164.

    Article  PubMed  Google Scholar 

  27. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ et al. Finding the missing heritability of complex diseases. Nature 2009; 461: 747–753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wasserman D, Geijer T, Rozanov V, Wasserman J . Suicide attempt and basic mechanisms in neural conduction: relationships to the SCN8A and VAMP4 genes. Am J Med Genet Part B 2005; 133B: 116–119.

    Article  CAS  PubMed  Google Scholar 

  29. Ben-Efraim YJ, Wasserman D, Wasserman J, Sokolowski M . Gene–environment interactions between CRHR1 variants and physical assault in suicide attempts. Genes Brain Behav 2011; 10: 663–672.

    Article  CAS  PubMed  Google Scholar 

  30. Wasserman D, Sokolowski M, Rozanov V, Wasserman J . The CRHR1 gene: a marker for suicidality in depressed males exposed to low stress. Genes Brain Behav 2008; 7: 14–19.

    CAS  PubMed  Google Scholar 

  31. Wasserman D, Wasserman J, Rozanov V, Sokolowski M . Depression in suicidal males: genetic risk variants in the CRHR1 gene. Genes Brain Behav 2009; 8: 72–79.

    Article  CAS  PubMed  Google Scholar 

  32. de Bakker PIW, Yelensky R, Pe’er I, Gabriel SB, Daly MJ, Altshuler D . Efficiency and power in genetic association studies. Nat Genet 2005; 37: 1217–1223.

    Article  CAS  PubMed  Google Scholar 

  33. The International HapMap Consortium. The International HapMap project. Nature 2003; 426: 789–796.

    Article  CAS  Google Scholar 

  34. Kerkhof AJFM, Bernasco W, Bille-Brahe U, Platt S, Schmidtke A . WHO/EURO Multicentre Study on Parasuicide: European Parasuicide Study Interview Schedule (EPSIS). Department of Clinical, Health and Personality Psychology, University of Leiden: Leiden, 1989.

    Google Scholar 

  35. World Health Organization. Composite International Diagnostic Interview (CIDI, version 2.1). WHO: Geneva, Switzerland, 1997.

  36. Kendler KS, Kuhn JW, Vittum J, Prescott CA, Riley B . The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: a replication. Arch Gen Psychiatry 2005; 62: 529–535.

    Article  CAS  PubMed  Google Scholar 

  37. Beck AT, Beck R, Kovacs M . Classification of suicidal behaviors: I. Quantifying intent and medical lethality. Am J Psychiatry 1975; 132: 285–287.

    Article  CAS  PubMed  Google Scholar 

  38. Barrett JC, Fry B, Maller J, Daly MJ . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics (Oxford, England) 2005; 21: 263–265.

    Article  CAS  Google Scholar 

  39. Reist C, Mazzanti C, Vu R, Fujimoto K, Goldman D . Inter-relationships of intermediate phenotypes for serotonin function, impulsivity, and a 5-HT2A candidate allele: His452Tyr. Mol Psychiatry 2004; 9: 871–878.

    Article  CAS  PubMed  Google Scholar 

  40. Schaid DJ, Sommer SS . Genotype relative risks: methods for design and analysis of candidate–gene association studies. Am J Hum Genet 1993; 53: 1114–1126.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Cordell HJ, Clayton DG . A unified stepwise regression procedure for evaluating the relative effects of polymorphisms within a gene using case/control or family data: application to HLA in type 1 diabetes. Am J Hum Genet 2002; 70: 124–141.

    Article  CAS  PubMed  Google Scholar 

  42. Hoffmann TJ, Lange C, Vansteelandt S, Laird NM . Gene–environment interaction tests for dichotomous traits in trios and sibships. Genet Epidemiol 2009; 33: 691–699.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lake SL, Laird NM . Tests of gene–environment interaction for case–parent triads with general environmental exposures. Ann Hum Genet 2004; 68: 55–64.

    Article  CAS  PubMed  Google Scholar 

  44. Beaty TH, Hetmanski JB, Zeiger JS, Fan YT, Liang KY, VanderKolk CA et al. Testing candidate genes for non-syndromic oral clefts using a case–parent trio design. Genet Epidemiol 2002; 22: 1–11.

    Article  PubMed  Google Scholar 

  45. Maestri NE, Beaty TH, Hetmanski J, Smith EA, McIntosh I, Wyszynski DF et al. Application of transmission disequilibrium tests to nonsyndromic oral clefts: including candidate genes and environmental exposures in the models. Am J Med Genet 1997; 73: 337–344.

    Article  CAS  PubMed  Google Scholar 

  46. Schaid DJ . Likelihoods and TDT for the case–parents design. Genet Epidemiol 1999; 16: 250–260.

    Article  CAS  PubMed  Google Scholar 

  47. Schaid DJ . General score tests for associations of genetic markers with disease using cases and their parents. Genet Epidemiol 1996; 13: 423–449.

    Article  CAS  PubMed  Google Scholar 

  48. Asimit J, Zeggini E . Rare variant association analysis methods for complex traits. Annu Rev Genet 2010; 44: 293–308.

    Article  CAS  PubMed  Google Scholar 

  49. Benjamini Y, Hochberg Y . Controlling the false discovery rate—a practical and powerful approach to multiple testing. J R Statist Soc Ser B 1995; 57: 289–300.

    Google Scholar 

  50. Storey JD . A direct approach to false discovery rates. J R Statist Soc Ser B 2002; 64: 479–498.

    Article  Google Scholar 

  51. Strimmer K . fdrtool: a versatile R package for estimating local and tail area-based false discovery rates. Bioinformatics 2008; 24: 1461–1462.

    Article  CAS  PubMed  Google Scholar 

  52. van den Oord EJCG, Sullivan PF . False discoveries and models for gene discovery. Trends Genet 2003; 19: 537–542.

    Article  CAS  PubMed  Google Scholar 

  53. Gauderman WJ . Sample size requirements for association studies of gene–gene interaction. Am J Epidemiol 2002; 155: 478–484.

    Article  PubMed  Google Scholar 

  54. Wolf JB, Cheverud JM, Roseman C, Hager R . Genome-wide analysis reveals a complex pattern of genomic imprinting in mice. PLoS Genet 2008; 4: e1000091.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Cockett NE, Jackson SP, Shay TL, Farnir F, Berghmans S, Snowder GD et al. Polar overdominance at the ovine callipyge locus. Science 1996; 273: 236–238.

    Article  CAS  PubMed  Google Scholar 

  56. 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: 166–172.

    Article  CAS  PubMed  Google Scholar 

  57. Arias B, Gasto C, Catalan R, Gutierrez B, Pintor L, Fananas L . The 5-HT(2A) receptor gene 102T/C polymorphism is associated with suicidal behavior in depressed patients. Am J Med Genet 2001; 105: 801–804.

    Article  CAS  PubMed  Google Scholar 

  58. McInnis MG, Lan TH, Willour VL, McMahon FJ, Simpson SG, Addington AM et al. Genome-wide scan of bipolar disorder in 65 pedigrees: supportive evidence for linkage at 8q24, 18q22, 4q32, 2p12, and 13q12. Mol Psychiatry 2003; 8: 288–298.

    Article  CAS  PubMed  Google Scholar 

  59. Wermter AK, Scherag A, Meyre D, Reichwald K, Durand E, Nguyen TT et al. Preferential reciprocal transfer of paternal/maternal DLK1 alleles to obese children: first evidence of polar overdominance in humans. Eur J Hum Genet 2008; 16: 1126–1134.

    Article  CAS  PubMed  Google Scholar 

  60. Fukuda Y, Koga M, Arai M, Noguchi E, Ohtsuki T, Horiuchi Y et al. Monoallelic and unequal allelic expression of the HTR2A gene in human brain and peripheral lymphocytes. Biol Psychiatry 2006; 60: 1331–1335.

    Article  CAS  PubMed  Google Scholar 

  61. Pastinen T, Sladek R, Gurd S, Sammak A, Ge B, Lepage P et al. A survey of genetic and epigenetic variation affecting human gene expression. Physiol Genomics 2004; 16: 184–193.

    Article  CAS  PubMed  Google Scholar 

  62. Bunzel R, Blumcke I, Cichon S, Normann S, Schramm J, Propping P et al. Polymorphic imprinting of the serotonin-2A (5-HT2A) receptor gene in human adult brain. Brain Res Mol Brain Res 1998; 59: 90–92.

    Article  CAS  PubMed  Google Scholar 

  63. Polesskaya OO, Sokolov BP . Differential expression of the ‘C’ and ‘T’ alleles of the 5-HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics. J Neurosci Res 2002; 67: 812–822.

    Article  CAS  PubMed  Google Scholar 

  64. Bray NJ, Buckland PR, Hall H, Owen MJ, O’Donovan MC . The serotonin-2A receptor gene locus does not contain common polymorphism affecting mRNA levels in adult brain. Mol Psychiatry 2004; 9: 109–114.

    Article  CAS  PubMed  Google Scholar 

  65. Cheverud JM, Lawson HA, Fawcett GL, Wang B, Pletscher LS, A RF et al. Diet-dependent genetic and genomic imprinting effects on obesity in mice. Obesity (Silver Spring) 2011; 19: 160–170.

    Article  Google Scholar 

  66. Lawson HA, Cady JE, Partridge C, Wolf JB, Semenkovich CF, Cheverud JM . Genetic effects at pleiotropic loci are context-dependent with consequences for the maintenance of genetic variation in populations. PLoS Genet 2011; 7: e1002256.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Polesskaya OO, Aston C, Sokolov BP . Allele C-specific methylation of the 5-HT2A receptor gene: evidence for correlation with its expression and expression of DNA methylase DNMT1. J Neurosci Res 2006; 83: 362–373.

    Article  CAS  PubMed  Google Scholar 

  68. Abdolmaleky HM, Yaqubi S, Papageorgis P, Lambert AW, Ozturk S, Sivaraman V et al. Epigenetic dysregulation of HTR2A in the brain of patients with schizophrenia and bipolar disorder. Schizophr Res 2011; 129: 183–190.

    Article  PubMed  Google Scholar 

  69. Falkenberg VR, Gurbaxani BM, Unger ER, Rajeevan MS . Functional genomics of serotonin receptor 2A (HTR2A): interaction of polymorphism, methylation, expression and disease association. Neuromol Med 2011; 13: 66–76.

    Article  CAS  Google Scholar 

  70. Ghadirivasfi M, Nohesara S, Ahmadkhaniha HR, Eskandari MR, Mostafavi S, Thiagalingam S et al. Hypomethylation of the serotonin receptor type-2A gene (HTR2A) at T102C polymorphic site in DNA derived from the saliva of patients with schizophrenia and bipolar disorder. Am J Med Genet B 2011; 156: 536–545.

    Article  CAS  Google Scholar 

  71. Comings DE, MacMurray JP . Molecular heterosis: a review. Mol Genet Metab 2000; 71: 19–31.

    Article  CAS  PubMed  Google Scholar 

  72. Salo J, Pulkki-Raback L, Hintsanen M, Lehtimaki T, Keltikangas-Jarvinen L . The interaction between serotonin receptor 2A and catechol-O-methyltransferase gene polymorphisms is associated with the novelty-seeking subscale impulsiveness. Psychiatr Genet 2010; 20: 273–281.

    Article  PubMed  Google Scholar 

  73. Cuartas Arias JM, Palacio Acosta CA, Valencia JG, Montoya GJ, Arango Viana JC, Nieto OC et al. Exploring epistasis in candidate genes for antisocial personality disorder. Psychiatr Genet 2011; 21: 115–124.

    Article  PubMed  Google Scholar 

  74. Wolf JB, Cheverud JM . A framework for detecting and characterizing genetic background-dependent imprinting effects. Mamm Genome 2009; 20: 681–698.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Piva F, Giulietti M, Nardi B, Bellantuono C, Principato G . An improved in silico selection of phenotype affecting polymorphisms in SLC6A4, HTR1A and HTR2A genes. Hum Psychopharmacol 2010; 25: 153–161.

    Article  CAS  PubMed  Google Scholar 

  76. Safran M, Dalah I, Alexander J, Rosen N, Iny Stein T, Shmoish M et al. GeneCards Version 3: the human gene integrator. Database (Oxford) 2010; 2010: baq020.

    Article  Google Scholar 

  77. Giegling I, Hartmann AM, Möller H-J, Rujescu D . Anger- and aggression-related traits are associated with polymorphisms in the 5-HT-2A gene. J Affect Disord 2006; 96: 75–81.

    Article  CAS  PubMed  Google Scholar 

  78. 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: 1518–1524.

    Article  CAS  PubMed  Google Scholar 

  79. 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: 33–41.

    Article  PubMed  Google Scholar 

  80. Fernando RL, Nettleton D, Southey BR, Dekkers JC, Rothschild MF, Soller M . Controlling the proportion of false positives in multiple dependent tests. Genetics 2004; 166: 611–619.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Meira-Lima I, Shavitt RG, Miguita K, Ikenaga E, Miguel EC, Vallada H . Association analysis of the catechol-o-methyltransferase (COMT), serotonin transporter (5-HTT) and serotonin 2A receptor (5HT2A) gene polymorphisms with obsessive-compulsive disorder. Genes Brain Behav 2004; 3: 75–79.

    Article  CAS  PubMed  Google Scholar 

  82. Paddock S, Laje G, Charney D, Rush AJ, Wilson AF, Sorant AJ et al. Association of GRIK4 with outcome of antidepressant treatment in the STAR*D cohort. Am J Psychiatry 2007; 164: 1181–1188.

    Article  PubMed  Google Scholar 

  83. 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. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 467–471.

    Article  CAS  PubMed  Google Scholar 

  84. Ribases M, Ramos-Quiroga JA, Hervas A, Bosch R, Bielsa A, Gastaminza X et al. Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB. Mol Psychiatry 2009; 14: 71–85.

    Article  CAS  PubMed  Google Scholar 

  85. Greenland S . The effect of misclassification in the presence of covariates. Am J Epidemiol 1980; 112: 564–569.

    Article  CAS  PubMed  Google Scholar 

  86. Garcia-Closas M, Thompson WD, Robins JM . Differential misclassification and the assessment of gene–environment interactions in case–control studies. Am J Epidemiol 1998; 147: 426–433.

    Article  CAS  PubMed  Google Scholar 

  87. Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE . Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am J Psychiatry 2010; 167: 509–527.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Manuck SB . The reaction norm in gene × environment interaction. Mol Psychiatry 2010; 15: 881–882.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank all interviewers at the Human Ecological Health organization/Odessa National Mechnikov University, Odessa, Ukraine; Professor Vsevolod Rozanov for coordination of the material collection in Ukraine; Dr Vladymyr Bogatov and laboratory technician Lars Holmberg for technical assistance; Dr Tatyana Reytarova for logistic assistance; and all those who have given their consent to participate as research subjects in this study. The study was funded by the Marianne and Marcus Wallenberg Foundation, the Knut and Alice Wallenberg Foundation, and the American Foundation for Suicide Prevention.

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  1. The National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), Karolinska Institute (KI), Stockholm, Sweden

    Y J Ben-Efraim, D Wasserman, J Wasserman & M Sokolowski

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Ben-Efraim, Y., Wasserman, D., Wasserman, J. et al. Family-based study of HTR2A in suicide attempts: observed gene, gene × environment and parent-of-origin associations. Mol Psychiatry 18, 758–766 (2013). https://doi.org/10.1038/mp.2012.86

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