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Human Genetics

, Volume 122, Issue 3–4, pp 409–411 | Cite as

Comments on the paper by D. Li and L. He: Meta-analysis shows association between the tryptophan hydroxylase (TPH) gene and schizophrenia

  • P. G. Sand
Letter to the Editors
In their recent paper, Li and He ( 2006) have provided what may be described as a “bulk meta-analysis” of genetic association data in schizophrenia, i.e. a set of three parallel meta-analyses involving multiple markers. Ideally, meta-analyses should improve the signal-to-noise ratio so that weak, yet robust effects may be appreciated more readily compared to consulting data from individual studies. This does not, however, eliminate confounders such as ethnic and diagnostic heterogeneity (Jablensky 2006). Intriguingly, Li and He have claimed an association between a TPH gene variant and schizophrenia using (a) pooled ethnicities, (b) pooled polymorphisms, and (c) pooled clinical entities. Their finding suggests the precautions proposed (Burchard et al. 2003) to ensure the homogeneity of samples prior to conducting meta-analyses are either unnecessary in general, or need not be applied to studies of schizophrenia. In other words, can we accelerate discovery by relaxing classification...

Keywords

Schizophrenia Personality Disorder Major Depressive Disorder Schizoaffective Disorder Invalid Data 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Bailar JC III (1997) The promise and problems of meta-analysis. N Engl J Med 337:559–561PubMedCrossRefGoogle Scholar
  2. Bennett PJ, McMahon WM, Watabe J, Achilles J, Bacon M, Coon H, Grey T, Keller T, Tate D, Tcaciuc I, Workman J, Gray D (2000) Tryptophan hydroxylase polymorphisms in suicide victims. Psychiatr Genet 10:13–17PubMedCrossRefGoogle Scholar
  3. Berman NG, Parker RA (2002) Meta-analysis: neither quick nor easy. BMC Med Res Methodol 2:10PubMedCrossRefGoogle Scholar
  4. Bleuler E (1911) Dementia praecox oder Gruppe der Schizophrenien. In: Aschaffenburg G (ed) Handbuch der Psychiatrie, Spez Teil, 4. Deuticke, Leipzig und WienGoogle Scholar
  5. Burchard EG, Ziv E, Coyle N, Gomez SL, Tang H, Karter AJ, Mountain JL, Perez-Stable EJ, Sheppard D, Risch N (2003) The importance of race and ethnic background in biomedical research and clinical practice. N Engl J Med 348:1170–1175PubMedCrossRefGoogle Scholar
  6. Chao HM, Richardson MA (2002) Aromatic amino acid hydroxylase genes and schizophrenia. Am J Med Genet 114:626–630PubMedCrossRefGoogle Scholar
  7. Chotai J, Serretti A, Lattuada E, Lorenzi C, Lilli R (2003) 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 119:99–111PubMedCrossRefGoogle Scholar
  8. Garver DL, Reich T, Isenberg KE, Cloninger CR (1989) Schizophrenia and the question of genetic heterogeneity. Schizophr Bull 15:421–430PubMedGoogle Scholar
  9. Ingles SA, Haile RW, Henderson BE, Kolonel LN, Nakaichi G, Shi CY, Yu MC, Ross RK, Coetzee GA (1997) Strength of linkage disequilibrium between two vitamin D receptor markers in five ethnic groups: implications for association studies. Cancer Epidemiol Biomarkers Prev 6:93–98PubMedGoogle Scholar
  10. Ioannidis JP, Ntzani EE, Trikalinos TA (2004) ‘Racial’ differences in genetic effects for complex diseases. Nat Genet 36:1312–1318PubMedCrossRefGoogle Scholar
  11. Jablensky A (2006) Subtyping schizophrenia: implications for genetic research. Mol Psychiatry 11:815–836PubMedCrossRefGoogle Scholar
  12. Jönsson E, Brene S, Geijer T, Terenius L, Tylec A, Persson ML, Sedvall G (1996) A search for association between schizophrenia and dopamine-related alleles. Eur Arch Psychiatry Clin Neurosci 246:297–304PubMedCrossRefGoogle Scholar
  13. Jönsson EG, Geijer T, Gyllander A, Terenius L, Sedvall GC (1998) Failure to replicate an association between a rare allele of a tyrosine hydroxylase gene microsatellite and schizophrenia. Eur Arch Psychiatry Clin Neurosci 248:61–63PubMedCrossRefGoogle Scholar
  14. Kunugi H, Ishida S, Kato T, Sakai T, Tatsumi M, Hirose T, Nanko S (1999) No evidence for an association of polymorphisms of the tryptophan hydroxylase gene with affective disorders or attempted suicide among Japanese patients. Am J Psychiatry 156:774–776PubMedGoogle Scholar
  15. Li D, He L (2006) Meta-analysis shows association between the tryptophan hydroxylase (TPH) gene and schizophrenia. Hum Genet 120:22–30PubMedCrossRefGoogle Scholar
  16. Newton-Cheh C, Hirschhorn JN (2005) Genetic association studies of complex traits: design and analysis issues. Mutat Res 573:54–69PubMedGoogle Scholar
  17. Ohtani M, Shindo S, Yoshioka N (2004) Polymorphisms of the tryptophan hydroxylase gene and serotonin 1A receptor gene in suicide victims among Japanese. Tohoku J Exp Med 202:123–133PubMedCrossRefGoogle Scholar
  18. Owen MJ (1992) Will schizophrenia become a graveyard for molecular geneticists? Psychol Med 22:289–293PubMedCrossRefGoogle Scholar
  19. Polymeropoulos MH, Xiao H, Rath DS, Merril CR (1991) Tetranucleotide repeat polymorphism at the human tyrosine hydroxylase gene (TH). Nucleic Acids Res 19:3753Google Scholar
  20. Richardson MA, Read LL, Clelland JD, Chao HM, Reilly MA, Romstad A, Suckow RF (2003) Phenylalanine hydroxylase gene in psychiatric patients: screening and functional assay of mutations. Biol Psychiatry 53:543–553PubMedCrossRefGoogle Scholar
  21. Rujescu D, Giegling I, Bondy B, Gietl A, Zill P, Moller HJ (2002) Association of anger-related traits with SNPs in the TPH gene. Mol Psychiatry 7:1023–1029PubMedCrossRefGoogle Scholar
  22. Sand PG, Eichhammer P, Langguth B, Hajak G (2006) COMT Association Data in Schizophrenia: New Caveats. Biol Psychiatry 60:663–664PubMedCrossRefGoogle Scholar
  23. Serretti A, Lilli R, Lorenzi C, Lattuada E, Cusin C, Smeraldi E (2001) Tryptophan hydroxylase gene and major psychoses. Psychiatry Res 103:79–86PubMedCrossRefGoogle Scholar
  24. Shinkai T, Ohmori O, Suzuki T, Kojima H, Hori H, Terao T, Nakamura J (2000) Polymorphisms of tryptophan hydroxylase gene and the symptomatology of schizophrenia: an association study. Psychiatr Genet 10:165–171PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of PsychiatryUniversity of RegensburgRegensburgGermany

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