Open Access

Susceptibility of schizophrenia and affective disorder not associated with loci on chromosome 6q in Han Chinese population

  • Zuowei Wang1, 3,
  • Yiru Fang1, 2Email author,
  • Shunying Yu2,
  • Chengmei Yuan1, 2,
  • Wu Hong1, 2,
  • Zhenghui Yi1, 2,
  • Sanduo Jiang2,
  • R Kelsoe John4 and
  • Zucheng Wang1
Behavioral and Brain Functions20073:46

https://doi.org/10.1186/1744-9081-3-46

Received: 18 June 2007

Accepted: 14 September 2007

Published: 14 September 2007

Abstract

Background

Several linkage studies across multiple population groups provide convergent support for susceptibility loci for schizophrenia – and, more recently, for affective disorder – on chromosome 6q. We explore whether schizophrenia and affective disorder have common susceptibility gene on 6q in Han Chinese population.

Methods

In the present study, we genotyped 45 family trios from Han Chinese population with mixed family history of schizophrenia and affective disorder. Twelve short tandem repeat (STRs) markers were selected, which covered 102.19 cM on chromosome 6q with average spacing 9.29 cM and heterozygosity 0.78. The transmission disequilibrium test (TDT) was performed to search for susceptibility loci to schizophrenia and affective disorder.

Results

The results showed STRs D6S257, D6S460, D6S1021, D6S292 and D6S1581 were associated with susceptibility to psychotic disorders. When families were grouped into schizophrenia and affective disorder group, D6S257, D6S460 and D6S1021, which map closely to the centromere of chromosome 6q, were associated with susceptibility to schizophrenia. Meanwhile, D6S1581, which maps closely to the telomere, was associated with susceptibility to affective disorder. But after correction of multiple test, all above association were changed into no significance (P > 0.05).

Conclusion

These results suggest that susceptibility of schizophrenia and affective disorder not associated with loci on chromosome 6q in Han Chinese population.

Background

The distinction between schizophrenia and affective disorder was historically based on distinct phenomenologies and long-term courses. A differential nosology and etiology was postulated, however never convincingly proven [1]. Opinions vary as to whether these disorders are etiologically distinct or represent points on a continuum of liability. Speculating from Kraepelin's view, schizophrenia does not aggregate in families of affective illness patients nor is there increased incidence of mood disorder in relatives of chronic schizophrenics. However, Rudin found risks of suffering from schizophrenia and mood disorder did not differ significantly among schizophrenic sibs [2]. Subsequently investigators found an increased risk of schizophrenic spectrum disorders among the first-degree relatives of probands with a family history of major mood disorders [3]. Conversely, relatives of probands with a family history of schizophrenic spectrum disorders were at a greater risk of affective illness than relatives of probands with no family history. Increasing evidence from molecular genetics also suggests an overlap in genetic susceptibility across the traditional classification systems. This has been suggested for linkage regions: 6q12-25, 13q32-q34 and 22q11-q22, and specific genes: DAOA(G72), DISC1, and NRG1 [4].

Several linkage studies across multiple population groups provide convergent support for susceptibility loci for schizophrenia – and, more recently, for affective disorder – on chromosome 6q. The first report of linkage findings on 6q13-26 in schizophrenia came from [5] which has accumulated support from a number of studies [617]. Recently, susceptibility loci to affective disorder were also reported to map to 6q [12, 1829], reviewed these results of positive linkage and association, and concluded that five regions (~91 Mb, ~113 Mb, ~126 Mb, ~133 Mb and ~162 Mb) could harbor susceptibility gene(s) to both schizophrenia and affective disorder. These phenomena lend support to the notion that affective disorder or a subset is associated with the liability to schizophrenia on chromosome 6q. In order to investigate whether schizophrenia and affective disorder have some genetic relationship on chromosome 6q, we recruited family trios with mixed family history of schizophrenia and affective disorder from the Han Chinese population for study using the transmission disequilibrium test (TDT).

Methods

Subjects

A mixed family was defined as one in which members suffer from both schizophrenia and affective disorder separately, namely at least one patient with schizophrenia and another patient with affective disorder among three-generation relatives. We recruited 45 family trios, composed of the probands and their biological parents, with mixed family history of schizophrenia and affective disorder. Here the probands were outpatients or inpatients from Shanghai Mental Health Center. Clinical diagnosis was made according to ICD-10; an independent clinician using the same criteria reviewed all diagnoses. Blood samples were obtained from the family trios. The investigation was carried out in accordance with the latest version of the Declaration of Helsinki, that the study design was reviewed by an appropriate ethical committee and that informed consent of the participants was obtained after the nature of the procedures had been fully explained. The probands included 21 male patients and 24 female ones, 26 diagnosed with schizophrenia and 19 with affective disorder (including 6 diagnosed with depressive disorder and 13 with single manic episode, respectively), mean age of patients were 28.7 ± 8.9 years, mean age of onset were 22.7 ± 8.0 years, mean duration were 5.9 ± 6.4 years; and the mean age of their parents were 58.5 ± 10.4 years.

Genotyping

Genomic DNA was extracted from peripheral blood leukocytes of each subject. The short tandem repeat (STR) markers used in this study were modified from the ABI PRISM Linkage Mapping Set Version 2.5. These included 12 STRs (D6S257, D6S460, D6S462, D6S1021, D6S1698, D6S1639, D6S262, D6S292, D6S308, D6S441, D6S1581, D6S1697) on chromosome 6q, which spanned 102.19 cM with a mean interval of 9.29 cM, heterozygosity of each STR above 0.50 and average heterozygosity 0.78 (see Table 1). Markers were amplified by polymerase chain reaction (PCR) with a Gene Amp PCR System 9700 (Perkin-Elmer, Foster City, CA). Electrophoresis was performed with an ABI PRISM 3730 sequencer (Perkin-Elmer). The PCR products were genotyped with ABI GeneMapper software (Perkin-Elmer).
Table 1

12 short tandem repeat (STR) markers used in this study

Marker

map position (cM)

polymorphisms

heterozygosity

D6S257

79.92

dinucleotide

0.87

D6S460

89.83

dinucleotide

0.82

D6S462

99.01

dinucleotide

0.66

D6S1021

112.20

trinucleotide

0.73

D6S1698

118.08

dinucleotide

0.82

D6S1639

124.11

dinucleotide

0.91

D6S262

130.00

dinucleotide

0.83

D6S292

136.97

dinucleotide

0.83

D6S308

144.46

dinucleotide

0.75

D6S441

154.10

dinucleotide

0.87

D6S1581

164.78

dinucleotide

0.72

D6S1697

182.11

dinucleotide

0.57

*12 STR markers are listed in turn according to map position. the polymorphism of D6S1021 is trinucleotide repeat, other markers are dinucleotide repeat. Heterozygosity of polymorphisms is between 0.57~0.91.

Statistical analysis

Hardy-Weinberg equilibrium and statistical differences in genotype and allele frequencies between probands and parents were evaluated using the χ2 test at a significance level of 0.05. Family-based association analyses was performed with applying the transmission disequilibrium test (TDT), where preferential allelic transmission from heterozygous parents to affected offspring is tested by applying (b-c)2/(b+c) statistics (Mc Nemar's equation) and χ2 test.

Results

The genotype distributions of total markers in the patient group and parent group did not deviate significantly from Hardy-Weinberg equilibrium in the patient or parent group (P > 0.05). Taking all family trios as study subjects, we found five STRs D6S257 at 79.92 cM, D6S460 at 89.83 cM, D6S1021 at 112.20 cM, D6S292 at 136.97 cM and D6S1581 at 164.78 cM were associated with susceptibility to psychotic disorders (see table 2). Then the family trios were grouped into schizophrenia group and affective disorder group according to diagnoses of probands and analyzed separately by TDT. We found that D6S257, D6S460 and D6S1021, which map closely to the centromere of chromosome 6q, were associated with susceptibility to schizophrenia. Meanwhile, D6S1581, which maps closely to the telomere, was associated with susceptibility to affective disorder. But after correction of multiple test, all above association were changed into no significance (P > 0.05).
Table 2

Transmission disequilibrium test (TDT) in total family trios

Marker

Allele

Transmitted

Non-transmitted

χ2

p-val

D6S257

173

0

4

4.00

0.046

D6S460

283

14

4

5.56

0.018

D6S460

287

2

9

4.45

0.035

D6S1021

134

0

4

4.00

0.046

D6S292

166

5

14

4.26

0.039

D6S1581

273

29

13

6.10

0.014

* Markers are Listed in table when p-val < 0.05.

Discussion

Heretofore the pathogenesis of schizophrenia and affective disorder have been unclear. Evidence from family, twin and adoption studies indicate that both genetic and environmental factors are involved in the etiology of these diseases. Molecular genetics studies suggest that they may be heterogenous and polygenic diseases. Despite the widely accepted view that schizophrenia and affective disorder represent independent illnesses and have different modes of inheritance, some data in the literature suggest that these diseases may share some genetic susceptibility. Many linkage analyses have suggested that the chromosome 6q region could harbor susceptibility loci to schizophrenia. Recently loci for affective disorder were reported to map in the 6q region. These results suggest that the relationship between chromosome 6q and susceptibility to schizophrenia or affective disorder deserves further study. Craddock et al [4] by meta-analysis and Kohn et al [29] by a topographic approach reviewed all reported results, and both concluded similarly that susceptibility genes to schizophrenia and affective disorder may both be located on chromosome 6q. Ewald et al [19] and Dick et al [20] reported positive linkage between D6S1021 and susceptibility to affective disorder.

The present study was performed in mixed pedigrees for schizophrenia and affective disorder to investigate whether two diseases share common genetic loci on 6q. Though primary results showed STRs D6S257, D6S460, D6S1021, D6S292 and D6S1581 were associated with susceptibility to psychotic disorders. Further grouped analysis showed that D6S257, D6S460 and D6S1021 were associated with susceptibility to schizophrenia, D6S1581 associated with susceptibility to affective disorder. But after correction of multiple tests, there is no significance association between loci on 6q and susceptibility of psychiatric disorders, including schizophrenia or affective disorder. These results suggest that susceptibility of schizophrenia and affective disorder not associated with loci on chromosome 6q in Han Chinese population. One of most limitations for the study is small sample size because of the mixed family trios with schizophrenia and affective disorders correspondingly too mall. For the reason, we did not differentiate the mean age of patients, mean age at onset, mean duration, etc. for both disorders to analyze. This and differences in population, allelic and locus heterogeneity may explain our inability to replicate some previous results. Future study is needed to collect a larger number of better-characterized trios in different population and avoid false negative association.

Conclusion

These results suggest that susceptibility of schizophrenia and affective disorder not associated with loci on chromosome 6q in our family trios of Han Chinese population.

Declarations

Acknowledgements

The National Natural Science Foundation (China, No 30270494), The Funds for Key Program in the National "10th 5-year Plan" of China (No 2004BA720A21-02), and the "863" Program of China (No 2006AA02Z430) supported this work for scientific research. We acknowledge Prof. Stephen V. Faraone (a BBF Editorial Board member) who gives some important suggestions in reviewing manuscript.

Authors’ Affiliations

(1)
Department of Psychiatry, School of Medicine, Shanghai JiaoTong University
(2)
Shanghai Mental Health Center
(3)
Hongkou Mental Health Center of Shanghai
(4)
Departments of Psychiatry, University of California, San Diego VA Healthcare System

References

  1. Maier W, Hofgen B, Zobel A, Rietschel M: Genetic models of schizophrenia and bipolar disorder: overlapping inheritance or discrete genotypes?. Eur Arch Psychiatry Clin Neurosci. 2005, 255: 159-166. 10.1007/s00406-005-0583-9.View ArticlePubMedGoogle Scholar
  2. Tsuang MT, Winokur G, Crowe RR: Morbidity risks of schizophrenia and affective disorders among first-degree relatives of patients with schizophrenia, mania, depression and surgical conditions. Br J Psychiatry. 1980, 137: 497-504.View ArticlePubMedGoogle Scholar
  3. Baron M, Gruen RS: Schizophrenia and affective disorder: are they genetically linked ?. Br J Psychiatry. 1991, 159: 267-270.View ArticlePubMedGoogle Scholar
  4. Craddock N, O'Donovan MC, Owen MJ: The genetics of schizophrenia and bipolar disorder: dissecting psychosis. J Med Genet. 2005, 42: 193-204. 10.1136/jmg.2005.030718.PubMed CentralView ArticlePubMedGoogle Scholar
  5. Cao Q, Martinez M, Zhang J, Sanders AR, Badner JA, Cravchik A, Markey CJ, Beshah E, Guroff JJ, Maxwell ME, Kazuba DM, Whiten R, Goldin LR, Gershon ES, Gejman PV: Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees. Genomics. 1997, 43: 1-8. 10.1006/geno.1997.4815.View ArticlePubMedGoogle Scholar
  6. Martinez M, Goldin LR, Cao Q, Zhang J, Sanders AR, Nancarrow DJ, Taylor JM, Levinson DF, Kirby A, Crowe RR, Andreasen NC, Black DW, Silverman JM, Lennon DP, Nertney DA, Brown DM, Mowry BJ, Gershon ES, Gejman PV: Follow-up study on a susceptibility locus for schizophrenia on chromosome 6q. Am J Med Genet. 1999, 88: 337-343. 10.1002/(SICI)1096-8628(19990820)88:4<337::AID-AJMG9>3.0.CO;2-A.View ArticlePubMedGoogle Scholar
  7. Kaufmann CA, Suarez B, Malaspina D, Pepple J, Svrakic D, Markel PD, Meyer J, Zambuto CT, Schmitt K, Matise TC, Harkavy Friedman JM, Hampe C, Lee H, Shore D, Wynne D, Faraone SV, Tsuang MT, Cloninger CR: NIMH Genetics Initiative Millenium Schizophrenia Consortium: linkage analysis of African-American pedigrees. Am J Med Genet. 1998, 81: 282-289. 10.1002/(SICI)1096-8628(19980710)81:4<282::AID-AJMG2>3.0.CO;2-W.View ArticlePubMedGoogle Scholar
  8. Levinson DF, Holmans P, Straub RE, Owen MJ, Wildenauer DB, Gejman PV, Pulver AE, Laurent C, Kendler KS, Walsh D, Norton N, Williams NM, Schwab SG, Lerer B, Mowry BJ, Sanders AR, Antonarakis SE, Blouin JL, DeLeuze JF, Mallet J: Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: schizophrenia linkage collaborative group III. Am J Hum Genet. 2000, 67: 652-663. 10.1086/303041.PubMed CentralView ArticlePubMedGoogle Scholar
  9. Bailer U, Leisch F, Meszaros K, Lenzinger E, Willinger U, Strobl R, Gebhardt C, Gerhard E, Fuchs K, Sieghart W, Kasper S, Hornik K, Aschauer HN: Genome scan for susceptibility loci for schizophrenia. Neuropsychobiology. 2000, 42: 175-182. 10.1159/000026690.View ArticlePubMedGoogle Scholar
  10. Edgar PF, Douglas JE, Cooper GJ, Dean B, Kydd R, Faull RLl: Comparative proteome analysis of the hippocampus implicates chromosome 6q in schizophrenia. Mol Psychiatry. 2000, 5: 85-90. 10.1038/sj.mp.4000580.View ArticlePubMedGoogle Scholar
  11. Lindholm E, Ekholm B, Shaw S, Jalonen P, Johansson G, Pettersson U, Sherrington R, Adolfsson R, Jazin E: A schizophrenia-susceptibility locus at 6q25, in one of the world's largest reported pedigrees. Am J Hum Genet. 2001, 69: 96-105. 10.1086/321288.PubMed CentralView ArticlePubMedGoogle Scholar
  12. Bailer U, Leisch F, Meszaros K, Lenzinger E, Willinger U, Strobl R, Heiden A, Gebhardt C, Doge E, Fuchs K, Sieghart W, Kasper S, Hornik K, Aschauer HN: Genome scan for susceptibility loci for schizophrenia and bipolar disorder. Biol Psychiatry. 2002, 52: 40-52. 10.1016/S0006-3223(02)01320-3.View ArticlePubMedGoogle Scholar
  13. Williams NM, Norton N, Williams H, Ekholm B, Hamshere ML, Lindblom Y, Chowdari KV, Cardno AG, Zammit S, Jones LA, Murphy KC, Sanders RD, McCarthy G, Gray MY, Jones G, Holmans P, Nimgaonkar V, Adolfson R, Osby U, Terenius L, Sedvall G, O'Donovan MC, Owen MJ: A systematic genomewide linkage study in 353 sib pairs with schizophrenia. Am J Hum Genet. 2003, 73: 1355-1367. 10.1086/380206.PubMed CentralView ArticlePubMedGoogle Scholar
  14. Lerer B, Segman RH, Hamdan A, Kanyas K, Karni O, Kohn Y, Korner M, Lanktree M, Kaadan M, Turetsky N, Yakir A, Kerem B, Macciardi F: Genome scan of Arab Israeli families maps a schizophrenia susceptibility gene to chromosome 6q23 and supports a locus at chromosome 10q24. Mol Psychiatry. 2003, 8: 488-498. 10.1038/sj.mp.4001322.View ArticlePubMedGoogle Scholar
  15. Lewis CM, Levinson DF, Wise LH, DeLisi LE, Straub RE, Hovatta I, Williams NM, Schwab SG, Pulver AE, Faraone SV, Brzustowicz LM, Kaufmann CA, Garver DL, Gurling HM, Lindholm E, Coon H, Moises HW, Byerley W, Shaw SH, Mesen A, Sherrington R, O'Neill FA, Walsh D, Kendler KS, Ekelund J, Paunio T, Lonnqvist J, Peltonen L, O'Donovan MC, Owen MJ: Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. Am J Hum Genet. 2003, 73: 34-48. 10.1086/376549.PubMed CentralView ArticlePubMedGoogle Scholar
  16. Duan J, Martinez M, Sanders AR, Hou C, Saitou N, Kitano T, Mowry BJ, Crowe RR, Silverman JM, Levinson DF, Gejman PV: Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia. Am J Hum Genet. 2004, 75: 624-638. 10.1086/424887.PubMed CentralView ArticlePubMedGoogle Scholar
  17. Levi A, Kohn Y, Kanyas K, Amann D, Pae CU, Hamdan A, Segman RH, Avidan N, Karni O, Korner M, Jun TY, Beckmann JS, Macciardi F, Lerer B: Fine mapping of a schizophrenia susceptibility locus at chromosome 6q23: increased evidence for linkage and reduced linkage interval. Eur J Hum Genet. 2005, 13: 763-771. 10.1038/sj.ejhg.5201406.View ArticlePubMedGoogle Scholar
  18. Bennett P, Segurado R, Jones I, Bort S, McCandless F, Lambert D, Heron J, Comerford C, Middle F, Corvin A, Pelios G, Kirov G, Larsen B, Mulcahy T, Williams N, O'Connell R, O'Mahony E, Payne A, Owen M, Holmans P, Craddock N, Gill M: The Wellcome trust UK-Irish bipolar affective disorder sibling-pair genome screen: first stage report. Mol Psychiatry. 2002, 7: 189-200. 10.1038/sj.mp.4000957.View ArticlePubMedGoogle Scholar
  19. Ewald H, Flint T, Kruse TA, Mors O: A genome-wide scan shows significant linkage between bipolar disorder and chromosome 12q24.3 and suggestive linkage to chromosomes 1p22-21, 4p16, 6q14-22, 10q26 and 16p13.3. Mol Psychiatry. 2002, 7: 734-744. 10.1038/sj.mp.4001074.View ArticlePubMedGoogle Scholar
  20. Dick DM, Foroud T, Flury L, Bowman ES, Miller MJ, Rau NL, Moe PR, Samavedy N, El-Mallakh R, Manji H, Glitz DA, Meyer ET, Smiley C, Hahn R, Widmark C, McKinney R, Sutton L, Ballas C, Grice D, Berrettini W, Byerley W, Coryell W, DePaulo R, MacKinnon DF, Gershon ES, Kelsoe JR, McMahon FJ, McInnis M, Murphy DL, Reich T: Genomewide linkage analyses of bipolar disorder: a new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative. Am J Hum Genet. 2003, 73: 107-114. 10.1086/376562.PubMed CentralView ArticlePubMedGoogle Scholar
  21. McInnis MG, Dick DM, Willour VL, Avramopoulos D, MacKinnon DF, Simpson SG, Potash JB, Edenberg HJ, Bowman ES, McMahon FJ, Smiley C, Chellis JL, Huo Y, Diggs T, Meyer ET, Miller M, Matteini AT, Rau NL, DePaulo JR, Gershon ES, Badner JA, Rice JP, Goate AM, Detera-Wadleigh SD, Nurnberger JI, Reich T, Zandi PP, Foroud TM: Genome-wide scan and conditional analysis in bipolar disorder: evidence for genomic interaction in the National Institute of Mental Health genetics initiative bipolar pedigrees. Biol Psychiatry. 2003, 54: 1265-1273. 10.1016/j.biopsych.2003.08.001.View ArticlePubMedGoogle Scholar
  22. Schulze TG, Buervenich S, Badner JA, Steele CJ, Detera-Wadleigh SD, Dick D, Foroud T, Cox NJ, MacKinnon DF, Potash JB, Berrettini WH, Byerley W, Coryell W, DePaulo JR, Gershon ES, Kelsoe JR, McInnis MG, Murphy DL, Reich T, Scheftner W, Nurnberger JI, McMahon FJ: Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees. Biol Psychiatry. 2004, 56: 18-23. 10.1016/j.biopsych.2004.04.004.View ArticlePubMedGoogle Scholar
  23. Pato CN, Pato MT, Kirby A, Petryshen TL, Medeiros H, Carvalho C, Macedo A, Dourado A, Coelho I, Valente J, Soares MJ, Ferreira CP, Lei M, Verner A, Hudson TJ, Morley CP, Kennedy JL, Azevedo MH, Daly MJ, Sklar P: Genome-wide scan in Portuguese Island families implicates multiple loci in bipolar disorder: fine mapping adds support on chromosomes 6 and 11. Am J Med Genet B Neuropsychiatr Genet. 2004, 127: 30-34. 10.1002/ajmg.b.30001.View ArticleGoogle Scholar
  24. Middleton FA, Pato MT, Gentile KL, Morley CP, Zhao X, Eisener AF, Brown A, Petryshen TL, Kirby AN, Medeiros H, Carvalho C, Macedo A, Dourado A, Coelho I, Valente J, Soares MJ, Ferreira CP, Lei M, Azevedo MH, Kennedy JL, Daly MJ, Sklar P, Pato CN: Genomewide linkage analysis of bipolar disorder by use of a high-density single-nucleotide-polymorphism (SNP) genotyping assay: a comparison with microsatellite marker assays and finding of significant linkage to chromosome 6q22. Am J Hum Genet. 2004, 74: 886-897. 10.1086/420775.PubMed CentralView ArticlePubMedGoogle Scholar
  25. Park N, Juo SH, Cheng R, Liu J, Loth JE, Lilliston B, Nee J, Grunn A, Kanyas K, Lerer B, Endicott J, Gilliam TC, Baron M: Linkage analysis of psychosis in bipolar pedigrees suggests novel putative loci for bipolar disorder and shared susceptibility with schizophrenia. Mol Psychiatry. 2004, 9: 1091-1099. 10.1038/sj.mp.4001541.View ArticlePubMedGoogle Scholar
  26. Park N, Cheng R, Juo SH, Liu J, Loth JE, Endicott J, Gilliam TC, Baron M: Absence of psychosis may influence linkage results for bipolar disorder. Mol Psychiatry. 2005, 10: 235-237. 10.1038/sj.mp.4001623.View ArticlePubMedGoogle Scholar
  27. Venken T, Claes S, Sluijs S, Paterson AD, van Duijn C, Adolfsson R, Del-Favero J, Van Broeckhoven C: Genomewide scan for affective disorder susceptibility loci in families of a northern Swedish isolated population. Am J Hum Genet. 2005, 76: 237-248. 10.1086/427836.PubMed CentralView ArticlePubMedGoogle Scholar
  28. Abou Jamra R, Sircar I, Becker T, Freudenberg-Hua Y, Ohlraun S, Freudenberg J, Brockschmidt F, Schulze TG, Gross M, Spira F, Deschner M, Schmäl C, Maier W, Propping P, Rietschel M, Cichon S, Nöthen MM, Schumacher J: A family-based and case-control association study of trace amine receptor genes on chromosome 6q23 in bipolar affective disorder. Mol Psychiatry. 2005, 10: 618-620. 10.1038/sj.mp.4001665.View ArticlePubMedGoogle Scholar
  29. Kohn Y, Lerer B: Excitement and confusion on chromosome 6q: the challenges of neuropsychiatriatric genetics in microcosm. Mol Psychiatry. 2005, 10: 1062-1073. 10.1038/sj.mp.4001738.View ArticlePubMedGoogle Scholar

Copyright

© Wang et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.