Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Research Article
  • Published:

Meta-analysis reveals association between serotonin transporter gene STin2 VNTR polymorphism and schizophrenia

Molecular Psychiatry volume 10, pages 928–938 (2005)Cite this article

Abstract

The serotonin transporter gene (SLC6A4) is a candidate gene for schizophrenia based on serotonin transporter's crucial role in serotonergic neurotransmission. However, association studies have produced conflicting results regarding the association between two common SLC6A4 gene polymorphisms, the promoter insertion/deletion (5-HTTLPR) and the intron 2 VNTR (STin2 VNTR) polymorphisms, and schizophrenia susceptibility. To further elucidate the putative association between the two SLC6A4 gene polymorphisms and schizophrenia susceptibility, we performed a meta-analysis based on all original published association studies between schizophrenia and the 5-HTTLPR and STin2 VNTR polymorphisms published before April 2004. Our analyses showed no statistically significant evidence for the association between the Short allele of the 5-HTTLPR polymorphism and schizophrenia (random-effects pooled odds ratio (OR)=0.99, 95% Confidence Interval (CI)=0.92–1.07, Z=−0.23, P=0.82) from 19 population-based association studies consisting of 2990 case and 3875 control subjects. However, highly significant evidence for association between the STin2.12 allele of the STin2 VNTR polymorphism (random-effects pooled OR=1.24, 95% CI=1.11–1.38, Z=3.82, P=0.00014) and schizophrenia was found from 12 population-based association studies consisting of 2177 cases and 2369 control subjects. Our meta-analysis suggests that the STin2.12 allele of the STin2 VNTR polymorphism is likely a risk factor for schizophrenia susceptibility. Our data imply that following completion of the International HapMap Project, a comprehensive evaluation of a set of markers that fully characterize the linkage disequilibrium relationships at the SLC6A4 gene should be tested in large well-characterized clinical samples in order to understand the role of this gene in schizophrenia susceptibility.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Gottesman II . Schizophrenia Genesis: The Origins of Madness. WH Freeman & Co.: New York, 1999.

    Google Scholar 

  2. McGuffin P, Owen MJ, Gottesman II . Psychiatric Genetics and Genomics, 1st edn. Oxford: Oxford University Press, 2002.

    Google Scholar 

  3. Knable MB, Weinberger DR . Dopamine, the prefrontal cortex and schizphrenia. J Psychopharmacol 1997; 11: 123–131.

    Article  CAS  PubMed  Google Scholar 

  4. Veenstra-VanderWeele J, Anderson GM, Cook Jr EH . Pharmacogenetics and the serotonin system: initial studies and future directions. Eur J Pharmacol 2000; 410: 165–181.

    Article  CAS  PubMed  Google Scholar 

  5. Collier DA, Li T . The genetics of schizophrenia: glutamate not dopamine? Eur J Pharmacol 2003; 480: 177–184.

    Article  CAS  PubMed  Google Scholar 

  6. Lesch KP, Moessner R . Genetically driven variation in serotonin uptake: is there a link to affective spectrum, neurodevelopmental, and neurodegenerative disorders? Biol Psychiatry 1998; 44: 179–192.

    Article  CAS  PubMed  Google Scholar 

  7. Torres GE, Gainetdinov RR, Caron MG . Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci 2003; 4: 13–25.

    Article  CAS  PubMed  Google Scholar 

  8. Joyce JN, Shane A, Lexov N, Winokur A, Casanova MF, Kleinman JE . Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenic. Neuropsychopharmacology 1993; 8: 315–336.

    Article  CAS  PubMed  Google Scholar 

  9. Naylor L, Dean B, Opeskin K, Pavey G, Hill C, Keks N et al. Changes in the serotonin transporter in the hippocampus of subjects with schizophrenia identified using [3H]paroxetine. J Neural Transm: Gen Sect 1996; 103: 749–757.

    Article  CAS  Google Scholar 

  10. Hernandez I, Sokolov BP . Abnormal expression of serotonin transporter mRNA in the frontal and temporal cortex of schizophrenics. Mol Psychiatry 1997; 2: 57–64.

    Article  CAS  PubMed  Google Scholar 

  11. Abdolmaleky HM, Faraone SV, Glatt SJ, Tsuang MT . Meta-analysis of association between the T102C polymorphism of the 5HT2a receptor gene and schizophrenia. Schizophr Res 2004; 67: 53–62.

    Article  PubMed  Google Scholar 

  12. Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS et al. Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci USA 1993; 90: 2542–2546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274: 1527–1531.

    Article  CAS  PubMed  Google Scholar 

  14. Nakamura M, Ueno S, Sano A, Tanabe H . The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants. Mol Psychiatry 2000; 5: 32–38.

    Article  CAS  PubMed  Google Scholar 

  15. Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D et al. Allelic variation of human serotonin transporter gene expression. J Neurochem 1996; 66: 2621–2624.

    Article  CAS  PubMed  Google Scholar 

  16. Lesch KP, Balling U, Gross J, Strauss K, Wolozin BL, Murphy DL et al. Organization of the human serotonin transporter gene. J Neural Transm Gen Sect 1994; 95: 157–162.

    Article  CAS  PubMed  Google Scholar 

  17. Kaiser R, Tremblay PB, Schmider J, Henneken M, Dettling M, Muller-Oerlinghausen B et al. Serotonin transporter polymorphisms: no association with response to antipsychotic treatment, but associations with the schizoparanoid and residual subtypes of schizophrenia. Mol Psychiatry 2001; 6: 179–185.

    Article  CAS  PubMed  Google Scholar 

  18. MacKenzie A, Quinn J . A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo. Proc Natl Acad Sci USA 1999; 96: 15251–15255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mendes de Oliveira JR, Otto PA, Vallada H, Lauriano V, Elkis H, Lafer B et al. Analysis of a novel functional polymorphism within the promoter region of the serotonin transporter gene (5-HTT) in Brazilian patients affected by bipolar disorder and schizophrenia. Am J Med Genet 1998; 81: 225–227.

    Article  CAS  PubMed  Google Scholar 

  20. Naylor L, Dean B, Pereira A, Mackinnon A, Kouzmenko A, Copolov D . No association between the serotonin transporter-linked promoter region polymorphism and either schizophrenia or density of the serotonin transporter in human hippocampus. Mol Med 1998; 4: 671–674.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Rao D, Jonsson EG, Paus S, Ganguli R, Nothen M, Nimgaonkar VL . Schizophrenia and the serotonin transporter gene. Psychiatr Genet 1998; 8: 207–212.

    Article  CAS  PubMed  Google Scholar 

  22. Stober G, Jatzke S, Heils A, Jungkunz G, Fuchs E, Knapp M et al. Susceptibility for schizophrenia is not influenced by a functional insertion/deletion variant in the promoter of the serotonin transporter gene. Eur Arch Psychiatry Clin Neurosci 1998; 248: 82–86.

    Article  CAS  PubMed  Google Scholar 

  23. Kotler M, Barak P, Cohen H, Averbuch IE, Grinshpoon A, Gritsenko I et al. Homicidal behavior in schizophrenia associated with a genetic polymorphism determining low catechol O-methyltransferase (COMT) activity. Am J Med Genet 1999; 88: 628–633.

    Article  CAS  PubMed  Google Scholar 

  24. 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: 101–106.

    Article  CAS  PubMed  Google Scholar 

  25. Hranilovic D, Schwab SG, Jernej B, Knapp M, Lerer B, Albus M et al. Serotonin transporter gene and schizophrenia: evidence for association/linkage disequilibrium in families with affected siblings. Mol Psychiatry 2000; 5: 91–95.

    Article  CAS  PubMed  Google Scholar 

  26. Shcherbatykh TV, Golimbet VE, Orlova VA, Kaleda VG . Polymorphism in the human serotonin transporter gene in endogenous psychoses. Genetika 2000; 36: 1712–1715.

    CAS  PubMed  Google Scholar 

  27. Tsai SJ, Hong CJ, Yu YW, Lin CH, Song HL, Lai HC et al. Association study of a functional serotonin transporter gene polymorphism with schizophrenia, psychopathology and clozapine response. Schizophr Res 2000; 44: 177–181.

    Article  CAS  PubMed  Google Scholar 

  28. Golimbet VE, Shcherbatykh TV, Abramova LI, Kaleda VG, Oleichik IV, Orlova VA et al. Serotonin transporter gene polymorphism in families with schizophrenia. Zh Nevrol Psikhiatr Im S S Korsakova 2001; 101: 40–41.

    CAS  PubMed  Google Scholar 

  29. Serretti A, Lilli R, Lorenzi C, Lattuada E, Cusin C, Smeraldi E . Serotonin transporter gene (5-HTTLPR) and major psychoses. Mol Psychiatry 2002; 7: 95–99.

    Article  CAS  PubMed  Google Scholar 

  30. 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 2003; 119B: 13–17.

    Article  CAS  PubMed  Google Scholar 

  31. Herken H, Erdal ME, Boke O, Savas HA . Tardive dyskinesia is not associated with the polymorphisms of 5-HT2A receptor gene, serotonin transporter gene and catechol-o-methyltransferase gene. Eur Psychiatry 2003; 18: 77–81.

    Article  PubMed  Google Scholar 

  32. Pae CU, Kim JJ, Lee SJ, Lee CU, Lee C, Paik IH et al. Polymorphism of the serotonin transporter gene and symptomatic dimensions of schizophrenia in the Korean population. Neuropsychobiology 2003; 47: 182–186.

    Article  CAS  PubMed  Google Scholar 

  33. Sun WW, Fan JB, Qian XQ, Tang JX, Xing YL, Shi JG et al. Transmission disequilibrium test of polymorphisms of serotonin transporter gene and schizophrenia based on family trios. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2003; 20: 342–344.

    CAS  PubMed  Google Scholar 

  34. Zainullina AG, Juriew EB, Bikbulatova SR, Khusnutdinova EK . Association of the hSERT and SLC6A4 polymorphic markers of the serotonin transporter gene with schizophrenia in two ethnic groups. Mol Biol 2003; 37: 508–512.

    Article  CAS  Google Scholar 

  35. Mata I, Arranz MJ, Patino A, Lai T, Beperet M, Sierrasesumaga L et al. Serotonergic polymorphisms and psychotic disorders in populations from North Spain. Am J Med Genet 2004; 126B: 88–94.

    Article  CAS  PubMed  Google Scholar 

  36. Malhotra AK, Goldman D, Mazzanti C, Clifton A, Breier A, Pickar D . A functional serotonin transporter (5-HTT) polymorphism is associated with psychosis in neuroleptic-free schizophrenics. Mol Psychiatry 1998; 3: 328–332.

    Article  CAS  PubMed  Google Scholar 

  37. Collier DA, Arranz MJ, Sham P, Battersby S, Vallada H, Gill P et al. The serotonin transporter is a potential susceptibility factor for bipolar affective disorder. Neuroreport 1996; 7: 1675–1679.

    Article  CAS  PubMed  Google Scholar 

  38. Liu W, Gu N, Feng G, Li S, Bai S, Zhang J et al. Tentative association of the serotonin transporter with schizophrenia and unipolar depression but not with bipolar disorder in Han Chinese. Pharmacogenetics 1999; 9: 491–495.

    CAS  PubMed  Google Scholar 

  39. Bonnet-Brilhault F, Laurent C, Thibaut F, Campion D, Chavand O, Samolyk D et al. Serotonin transporter gene polymorphism and schizophrenia: an association study. Biol Psychiatry 1997; 42: 634–636.

    Article  CAS  PubMed  Google Scholar 

  40. Dimitrova A, Georgieva L, Nikolov I, Poriazova N, Krastev S, Toncheva D et al. Major psychiatric disorders and the serotonin transporter gene (SLC6A4): family-based association studies. Psychiatr Genet 2002; 12: 137–141.

    Article  PubMed  Google Scholar 

  41. Tsai SJ, Ouyang WC, Hong CJ . Association for serotonin transporter gene variable number tandem repeat polymorphism and schizophrenic disorders. Neuropsychobiology 2002; 45: 131–133.

    Article  CAS  PubMed  Google Scholar 

  42. Altshuler D, Daly M, Kruglyak L . Guilt by association. Nat Genet 2000; 26: 135–137.

    Article  CAS  PubMed  Google Scholar 

  43. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG . Replication validity of genetic association studies. Nat Genet 2001; 29: 306–309.

    Article  CAS  PubMed  Google Scholar 

  44. Hirschhorn JN, Altshuler D . Once and again-issues surrounding replication in genetic association studies. J Clin Endocrinol Metab 2002; 87: 4438–4441.

    Article  CAS  PubMed  Google Scholar 

  45. Mulrow CD . Rationale for systematic reviews. BMJ 1994; 309: 597–599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lau J, Ioannidis JP, Schmid CH . Summing up evidence: one answer is not always enough. Lancet 1998; 351: 123–127.

    Article  CAS  PubMed  Google Scholar 

  47. Cohn LD, Becker BJ . How meta-analysis increases statistical power. Psychol Methods 2003; 8: 243–253.

    Article  PubMed  Google Scholar 

  48. Munafo MR, Flint J . Meta-analysis of genetic association studies. Trends Genet 2004; 20: 439–444.

    Article  CAS  PubMed  Google Scholar 

  49. Faraone SV, Doyle AE, Mick E, Biederman J . Meta-analysis of the association between the 7-repeat allele of the dopamine D4 receptor gene and attention deficit. Am J Psychiatry 2001; 158: 1052–1057.

    Article  CAS  PubMed  Google Scholar 

  50. Glatt SJ, Faraone SV, Tsuang MT . Association between a functional catechol O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case–control and family-based studies. Am J Psychiatry 2003; 160: 469–476.

    Article  PubMed  Google Scholar 

  51. Serretti A, Catalano M, Smeraldi E . Serotonin transporter gene is not associated with symptomatology of schizophrenia. Schizophr Res 1999; 35: 33–39.

    Article  CAS  PubMed  Google Scholar 

  52. Arranz MJ, Bolonna AA, Munro J, Curtis CJ, Collier DA, Kerwin RW . The serotonin transporter and clozapine response. Mol Psychiatry 2000; 5: 124–125.

    Article  CAS  PubMed  Google Scholar 

  53. Chong SA, Tan EC, Tan CH, Mahendren R, Tay AH, Chua HC . Tardive dyskinesia is not associated with the serotonin gene polymorphism (5-HTTLPR) in Chinese. Am J Med Genet 2000; 96: 712–715.

    Article  CAS  PubMed  Google Scholar 

  54. Segman RH, Goltser T, Heresco-Levy U, Finkel B, Shalem R, Schlafman M et al. Association of dopaminergic and serotonergic genes with tardive dyskinesia in patients with chronic schizophrenia. Pharmacogenomics J 2003; 3: 277–283.

    Article  CAS  PubMed  Google Scholar 

  55. Nolan KA, Volavka J, Lachman HM, Saito T . An association between a polymorphism of the tryptophan hydroxylase gene and aggression in schizophrenia and schizoaffective disorder. Psychiatr Genet 2000; 10: 109–115.

    Article  CAS  PubMed  Google Scholar 

  56. Herken H, Erdal ME, Aynacioglu AS, Barlas O, Cataloluk O, Esgi K et al. Frequency of the 17-bp variable number of tandem repeat polymorphism in Turkish schizophrenic patients. Schizophr Res 2002; 58: 99–100.

    Article  PubMed  Google Scholar 

  57. Chotai J, Serretti A, Lattuada E, Lorenzi C, Lilli R . Gene–environment interaction in psychiatric disorders as indicated by season of birth variations in tryptophan hydroxylase (TPH), serotonin transporter (5-HTTLPR) and dopamine receptor (DRD4) gene polymorphisms. Psychiatry Res 2003; 119: 99–111.

    Article  CAS  PubMed  Google Scholar 

  58. Golimbet VE, Alfimova MV, Shcherbatikh T, Kaleda VG, Abramova LI, Rogaev EI . Serotonin transporter gene polymorphism and schizoid personality traits in the patients with psychosis and psychiatrically well subjects. World J Biol Psychiatry 2003; 4: 25–29.

    Article  PubMed  Google Scholar 

  59. Zainullina AG, Iur'ev EB, Bikbulatova SR, Khusnutdinova EK . Association of the hSERT and SLC6A4 polymorphic markers of the serotonin transporter gene with schizophrenia in different ethnic groups. Mol Biol (Mosk) 2003; 37: 601–606.

    Article  CAS  Google Scholar 

  60. Mantel N, Haenszel W . Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22: 719–748.

    CAS  PubMed  Google Scholar 

  61. DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–188.

    Article  CAS  PubMed  Google Scholar 

  62. Egger M, Davey Smith G, Schneider M, Minder C . Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–634.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Spielman RS, McGinnis RE, Ewens WJ . Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 1993; 52: 506–516.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Song Y, Niu T, Manson JE, Kwiatkowski DJ, Liu S . Are variants in the CAPN10 gene related to risk of type 2 diabetes? A quantitative assessment of population and family-based association studies. Am J Hum Genet 2004; 74: 208–222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN . Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 2003; 33: 177–182.

    Article  CAS  PubMed  Google Scholar 

  66. Cappelleri JC, Ioannidis JP, Schmid CH, de Ferranti SD, Aubert M, Chalmers TC et al. Large trials vs meta-analysis of smaller trials: how do their results compare? JAMA 1996; 276: 1332–1338.

    Article  CAS  PubMed  Google Scholar 

  67. The International HapMap Consortium. The International HapMap Project. Nature 2003; 426: 789–796.

  68. Daly MJ, Rioux JD, Schaffner SF, Hudson TJ, Lander ES . High-resolution haplotype structure in the human genome. Nat Genet 2001; 29: 229–232.

    Article  CAS  PubMed  Google Scholar 

  69. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B et al. The structure of haplotype blocks in the human genome. Science 2002; 296: 2225–2229.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  71. Hedrick PW . Gametic disequilibrium measures: proceed with caution. Genetics 1987; 117: 331–341.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Gelernter J, Cubells JF, Kidd JR, Pakstis AJ, Kidd KK . Population studies of polymorphisms of the serotonin transporter protein gene. Am J Med Genet 1999; 88: 61–66.

    Article  CAS  PubMed  Google Scholar 

  73. 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 

  74. Anguelova M, Benkelfat C, Turecki G . A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders. Mol Psychiatry 2003; 8: 574–591.

    CAS  PubMed  Google Scholar 

  75. Munafo MR, Clark TG, Moore LR, Payne E, Walton R, Flint J . Genetic polymorphisms and personality in healthy adults: a systematic review and meta-analysis. Mol Psychiatry 2003; 8: 471–484.

    Article  CAS  PubMed  Google Scholar 

  76. Sen S, Burmeister M, Ghosh D . Meta-analysis of the association between a serotonin transporter promoter polymorphism (5-HTTLPR) and anxiety-related personality traits. Am J Med Genet 2004; 127B: 85–89.

    Article  PubMed  Google Scholar 

  77. Schinka JA, Busch RM, Robichaux-Keene N . A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety. Mol Psychiatry 2004; 9: 197–202.

    Article  CAS  PubMed  Google Scholar 

  78. Lasky-Su JA, Faraone SV, Glatt SJ, Tsuang MT . Meta-analysis of the association between two polymorphisms in the serotonin transporter gene and affective disorders. Am J Med Genet 2005; 133: 110–115.

    Article  Google Scholar 

  79. Purcell S, Cherny SS, Sham PC . Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 2003; 19: 149–150.

    Article  CAS  PubMed  Google Scholar 

  80. Ardlie KG, Lunetta KL, Seielstad M . Testing for population subdivision and association in four case–control studies. Am J Hum Genet 2002; 71: 304–311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hranilovic D, Stefulj J, Schwab S, Borrmann-Hassenbach M, Albus M, Jernej B et al. Serotonin transporter promoter and intron 2 polymorphisms: relationship between allelic variants and gene expression. Biol Psychiatry 2004; 55: 1090–1094.

    Article  CAS  PubMed  Google Scholar 

  82. Jonsson EG, Nothen MM, Gustavsson JP, Neidt H, Bunzel R, Propping P et al. Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes and their relationships to monoamine metabolite concentrations in CSF of healthy volunteers. Psychiatry Res 1998; 79: 1–9.

    Article  CAS  PubMed  Google Scholar 

  83. Fiskerstrand CE, Lovejoy EA, Quinn JP . An intronic polymorphic domain often associated with susceptibility to affective disorders has allele dependent differential enhancer activity in embryonic stem cells. FEBS Lett 1999; 458: 171–174.

    Article  CAS  PubMed  Google Scholar 

  84. Lovejoy EA, Scott AC, Fiskerstrand CE, Bubb VJ, Quinn JP . The serotonin transporter intronic VNTR enhancer correlated with a predisposition to affective disorders has distinct regulatory elements within the domain based on the primary DNA sequence of the repeat unit. Eur J Neurosci 2003; 17: 417–420.

    Article  CAS  PubMed  Google Scholar 

  85. Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003; 423: 506–511.

    Article  CAS  PubMed  Google Scholar 

  86. Mukai J, Liu H, Burt RA, Swor DE, Lai WS, Karayiorgou M et al. Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia. Nat Genet 2004; 36: 725–731.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr Nan Laird, Dr Tracey Petryshen, Dr Shaun Purcell, Dr Roy Perlis, Dr Jang woo Kim and Anthony Tahl for critical reviews and helpful discussion of the manuscript, Kimberly Aldinger and Skye Waggoner for technical assistances, and Andrew Kirby and Tracey Petryshen for Locusview software. We thank the International HapMap Consortium and the International HapMap project, and Dr Vera Golimbet and Dr RH Segman for generously sharing genotype data and for answering specific questions regarding their studies.

Author information

Authors and Affiliations

  1. Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Charlestown, MA, USA

    J B Fan & P Sklar

  2. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    J B Fan & P Sklar

  3. Department of Psychiatry, Harvard Medical School, Boston, MA, USA

    P Sklar

Authors
  1. J B Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Sklar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P Sklar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fan, J., Sklar, P. Meta-analysis reveals association between serotonin transporter gene STin2 VNTR polymorphism and schizophrenia. Mol Psychiatry 10, 928–938 (2005). https://doi.org/10.1038/sj.mp.4001690

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001690

Keywords

This article is cited by

Search

Advanced search

Quick links