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Family-based association studies of monoaminergic gene polymorphisms among North Indians with schizophrenia

Molecular Psychiatry volume 6, pages 220–224 (2001)Cite this article

Abstract

Associations between schizophrenia and four candidate genes were tested among Indian patients with schizophrenia and their parents (DSM-IV criteria, n = 179 families). Polymorphisms within the genes encoding the serotonin 2A receptor (HT2A), tryptophan hydroxylase (TPH), catechol-O-methyl transferase (COMT) and dopamine transporter (DAT) were thus investigated. Two polymorphisms each were analyzed at HT2A and TPH, enabling haplotype-based analyses using the transmission disequilibrium test (TDT) for these genes. No significant associations were detected. Pooled analysis of samples like ours may be necessary to definitively exclude putative allelic associations at these loci.

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References

  1. Moldin SO . The maddening hunt for madness genes Nature Genet 1997 17: 127–129

    Article  CAS  PubMed  Google Scholar 

  2. Risch N, Merikangas K . The future of genetic studies of complex human diseases Science 1996 273: 1516–1517

    Article  CAS  PubMed  Google Scholar 

  3. O'Donovan MC, Owen MJ . Candidate gene-association studies of schizophrenia Am J Hum Genet 1999 65: 587–592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Spielman RS, Ewens WJ . The TDT and other family-based tests for linkage disequilibrium and association [editorial] Am J Hum Genet 1996 59: 983–989

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Inayama Y, Yoneda H, Ishida T, Nonomura Y, Kono Y, Koh J et al. An association between schizophrenia and a serotonin receptor DNA marker (5HTR2) Neuropsychopharmacology 1994 10: 56S

    Google Scholar 

  6. Ohara K, Nagai M, Tani K, Tsukamoto T . Schizophrenia and the serotonin-2A receptor promoter polymorphism Psychiatry Res 1999 85: 221–224

    Article  CAS  PubMed  Google Scholar 

  7. Lin CH, Tsai SJ, Yu YW, Song HL, Tu PC, Sim CB et al. No evidence for association of serotonin-2A receptor variant (102T/C) with schizophrenia or clozapine response in a Chinese population Neuroreport 1999 10: 57–60

    Article  CAS  PubMed  Google Scholar 

  8. Spurlock G, Williams J, Daniels J, Owen M, McGuffin P . The European multi-centre study of susceptibility gene associations in schizophrenia: typing the 5HT-2R gene Psychiatr Genet 1995 5: 64–65

    Google Scholar 

  9. Nielsen DA, Virkkunen M, Lappalainen J, Eggert M, Brown GL, Long JC et al. A tryptophan hydroxylase gene marker for suicidality and alcoholism Arch Gen Psychiatry 1998 55: 593–602

    Article  CAS  PubMed  Google Scholar 

  10. Serretti A, Lilli R, Lorenzi C, Lattuada E, Cusin C, Smeraldi E . Lack of association between tryptophan hydroxylase gene and psychotic symptomatology in schizophrenia Schizophr Res 1999 40: 171–172

    Article  CAS  PubMed  Google Scholar 

  11. Rotondo A, Schuebel K, Bergen A, Aragon R, Virkkunen M, Linnoila M et al. Identification of four variants in the tryptophan hydroxylase promoter and association to behavior Mol Psychiatry 1999 4: 360–368

    Article  CAS  PubMed  Google Scholar 

  12. Sano A, Kondoh K, Kakimoto Y, Kondo I . A 40-nucleotide repeat polymorphism in the human dopamine transporter gene Hum Genet 1993 91: 405–406

    Article  CAS  PubMed  Google Scholar 

  13. Persico AM, Macciardi F . Genotypic association between dopamine transporter gene polymorphisms and schizophrenia Am J Med Genet 1997 74: 53–57

    Article  CAS  PubMed  Google Scholar 

  14. Blum K, Braverman ER, Wu S, Cull JG, Chen TJ, Gill J et al. Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid/avoidant behaviors (SAB) Mol Psychiatry 1997 2: 239–246

    Article  CAS  PubMed  Google Scholar 

  15. Bassett AS, Chow EW . 22q11 deletion syndrome: a genetic subtype of schizophrenia Biol Psychiatry 1999 46: 882–891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. de Chaldee M, Laurent C, Thibaut F, Martinez M, Samolyk D, Petit M et al. Linkage disequilibrium on the COMT gene in French schizophrenics and controls Am J Med Genet 1999 88: 452–457

    Article  CAS  PubMed  Google Scholar 

  17. Ohmori O, Shinkai T, Kojima H, Terao T, Suzuki T, Mita T et al. Association study of a functional catechol-O-methyltransferase gene polymorphism in Japanese schizophrenics Neurosci Lett 1998 243: 109–112

    Article  CAS  PubMed  Google Scholar 

  18. Lachman HM, Nolan KA, Mohr P, Saito T, Volavka J . Association between catechol O-methyltransferase genotype and violence in schizophrenia and schizoaffective disorder Am J Psychiatry 1998 155: 835–837

    CAS  PubMed  Google Scholar 

  19. Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM . Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders Pharmacogenetics 1996 6: 243–250

    Article  CAS  PubMed  Google Scholar 

  20. Li T, Ball D, Zhao J, Murray RM, Liu X, Sham PC et al. Family-based linkage disequilibrium mapping using SNP marker haplotypes: application to a potential locus for schizophrenia at chromosome 22q11 Mol Psychiatry 2000 5: 77–84

    Article  CAS  PubMed  Google Scholar 

  21. Chen CH, Lee YR, Chung MY, Wei FC, Koong FJ, Shaw CK et al. Systematic mutation analysis of the catechol O-methyltransferase gene as a candidate gene for schizophrenia Am J Psychiatry 1999 156: 1273–1275

    CAS  PubMed  Google Scholar 

  22. Karayiorgou M, Gogos JA, Galke BL, Wolyniec PS, Nestadt G, Antonarakis SE et al. Identification of sequence variants and analysis of the role of the catechol-O-methyl-transferase gene in schizophrenia susceptibility Biol Psychiatry 1998 43: 425–431

    Article  CAS  PubMed  Google Scholar 

  23. Passarino G, Semino O, Bernini LF, Santachiara-Benerecetti AS . Pre-Caucasoid and Caucasoid genetic features of the Indian population, revealed by mtDNA polymorphisms Am J Hum Genet 1996 59: 927–934

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Prasad S, Deshpande S, Bhatia T, Wood J, Nimgaonkar V, Thelma BK . An association study of schizophrenia among Indian families Am J Med Genet 1999 88: 298–300

    Article  CAS  PubMed  Google Scholar 

  25. Knapp M . A note on power approximations for the transmission/disequilibrium test Am J Hum Genet 1999 64: 1177–1185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhao JH, Sham PC, Curtis D . A program for the Monte Carlo evaluation of significance of the extended transmission/disequilibrium test [letter] Am J Hum Genet 1999 64: 1484–1485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES . Parametric and non-parametric linkage analysis: a unified multipoint approach Am J Hum Genet 1996 58: 1347–1363

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Warren JT, Peacock ML, Rodriguez LC, Fink JK . An MspI polymorphism in the human serotonic receptor gene (HTR2): detection by DGGE and RFLP analysis Hum Mol Genet 1993 2: 338

    Article  CAS  PubMed  Google Scholar 

  29. Nielsen DA, Dean M, Goldman D . Genetic mapping of the human tryptophan hydroxylase gene on chromosome 11, using an intronic conformational polymorphism Am J Hum Genet 1992 51: 1366–1371

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Daniels JK, Williams NM, Williams J, Jones LA, Cardno AG, Murphy KC et al. No evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol O-methyltransferase activity Am J Psychiatry 1996 153: 268–270

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was funded in part by grants from the National Institute of Mental Health, the Fogarty International Center and the US India fund (No. K02 MH 01489, No. R03 TW00730 to VLN and Indo-US Project Agreement No. N-443–645) to VLN, BKT, SND and Senior Research Fellowship from Council of Scientific and Industrial Research, New Delhi, to SP. We thank K Chowdari, PhD for helpful advice. We thank the following physicians and colleagues for advice and help with ascertainment: SP Aggarwal, CP Singh, N Bohra, D Mohan, BR Agnihotri, R Rastogi, RK Singh, RC Jiloha, S Mittal, H Matai, RK Chadha; K Kumar, A Lal, PL Chawla, DN Mandekar, PK Shrivastva, AK Sharma, R Sagar, M Batra, A Kumar, HC Raheja, MNL Mathur, AK Das, SK Das, U Goswami, U Khastgir, R Nagpal, SM Pahwa, Ms Sushma, Ms V Sood, Mrs M Zutshi.

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Authors and Affiliations

  1. Department of Genetics, University of Delhi South Campus, New Delhi, India

    P Semwal, S Prasad & B K Thelma

  2. Indo-US Project on Schizophrenia Genetics, New Delhi, India

    S Prasad, T Bhatia, S N Deshpande & V L Nimgaonkar

  3. Department of Psychiatry, Dr RML Hospital, New Delhi, India

    S N Deshpande

  4. Department of Psychiatry, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, PA, USA

    J Wood & V L Nimgaonkar

  5. Department of Human Genetics, University of Pittsburgh School of Medicine and Graduate School of Public Health, Pittsburgh, PA, USA

    V L Nimgaonkar

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  1. P Semwal
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Semwal, P., Prasad, S., Bhatia, T. et al. Family-based association studies of monoaminergic gene polymorphisms among North Indians with schizophrenia. Mol Psychiatry 6, 220–224 (2001). https://doi.org/10.1038/sj.mp.4000839

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