Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations

T Li, F Zhang, X Liu, X Sun, P C Sham, C Crombie, X Ma, Q Wang, H Meng, W Deng, P Yates, X Hu, N Walker, R M Murray, D St Clair, D A Collier

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Abstract

The dystrobrevin-binding protein 1 (DTNBP1) gene on chromosome 6p has emerged as a potential susceptibility gene for schizophrenia. Although a number of attempts to replicate the original association finding have been successful, they have not identified any obvious pathogenic variants or a single at risk haplotype common to all populations studied. In the present study we attempted further replication in an independent sample of 638 nuclear families from the Han Chinese population of Sichuan Province, SW China. We also examined 580 Scottish schizophrenic cases and 620 controls. We genotyped 10 single-nucleotide polymorphisms ( SNPs) in DTNBP1 that were used in the original report of association, plus rs2619538 ( SNP 'A') in the putative promoter region, which has also been associated with schizophrenia. In the Chinese trios we found that two SNPs (P1635 and P1765) were significantly overtransmitted, but with alleles opposite to those reported in the original studies. SNPs P1757 and P1765 formed a common haplotype, which also showed significant overtransmission. In the Scottish cases and controls, no individual markers were significantly associated with schizophrenia. A single haplotype, which included rs2619538 and P1583, and one rare haplotype, composed of P1320 and P1757, were significantly associated with schizophrenia, but no previously reported haplotypes were associated. Based on the data from the Chinese population, our results provide statistical support for DTNBP1 as a susceptibility gene for schizophrenia, albeit with haplotypes different from those of the original study. However, our lack of replication in the Scottish samples also indicates that caution is warranted when evaluating the robustness of the evidence for DTNBP1 as genetic risk factor for schizophrenia.

Original languageEnglish
Pages (from-to)1037-1044
Number of pages8
JournalMolecular Psychiatry
Volume10
DOIs
Publication statusPublished - 2005

Keywords

  • psychosis
  • association
  • 6p
  • dysbindin
  • dystrobrevin
  • LINKAGE-DISEQUILIBRIUM
  • DYSBINDIN GENE
  • BIPOLAR DISORDER
  • 6P22.3 GENE
  • ASSOCIATION
  • COMPLEX
  • IDENTIFICATION
  • METAANALYSIS
  • BIOGENESIS
  • EXPRESSION

Cite this

Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations. / Li, T ; Zhang, F ; Liu, X ; Sun, X ; Sham, P C ; Crombie, C ; Ma, X ; Wang, Q ; Meng, H ; Deng, W ; Yates, P ; Hu, X ; Walker, N ; Murray, R M ; St Clair, D ; Collier, D A .

In: Molecular Psychiatry, Vol. 10, 2005, p. 1037-1044.

Research output: Contribution to journalArticle

Li, T, Zhang, F, Liu, X, Sun, X, Sham, PC, Crombie, C, Ma, X, Wang, Q, Meng, H, Deng, W, Yates, P, Hu, X, Walker, N, Murray, RM, St Clair, D & Collier, DA 2005, 'Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations', Molecular Psychiatry, vol. 10, pp. 1037-1044. https://doi.org/10.1038/sj.mp.4001718
Li, T ; Zhang, F ; Liu, X ; Sun, X ; Sham, P C ; Crombie, C ; Ma, X ; Wang, Q ; Meng, H ; Deng, W ; Yates, P ; Hu, X ; Walker, N ; Murray, R M ; St Clair, D ; Collier, D A . / Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations. In: Molecular Psychiatry. 2005 ; Vol. 10. pp. 1037-1044.
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abstract = "The dystrobrevin-binding protein 1 (DTNBP1) gene on chromosome 6p has emerged as a potential susceptibility gene for schizophrenia. Although a number of attempts to replicate the original association finding have been successful, they have not identified any obvious pathogenic variants or a single at risk haplotype common to all populations studied. In the present study we attempted further replication in an independent sample of 638 nuclear families from the Han Chinese population of Sichuan Province, SW China. We also examined 580 Scottish schizophrenic cases and 620 controls. We genotyped 10 single-nucleotide polymorphisms ( SNPs) in DTNBP1 that were used in the original report of association, plus rs2619538 ( SNP 'A') in the putative promoter region, which has also been associated with schizophrenia. In the Chinese trios we found that two SNPs (P1635 and P1765) were significantly overtransmitted, but with alleles opposite to those reported in the original studies. SNPs P1757 and P1765 formed a common haplotype, which also showed significant overtransmission. In the Scottish cases and controls, no individual markers were significantly associated with schizophrenia. A single haplotype, which included rs2619538 and P1583, and one rare haplotype, composed of P1320 and P1757, were significantly associated with schizophrenia, but no previously reported haplotypes were associated. Based on the data from the Chinese population, our results provide statistical support for DTNBP1 as a susceptibility gene for schizophrenia, albeit with haplotypes different from those of the original study. However, our lack of replication in the Scottish samples also indicates that caution is warranted when evaluating the robustness of the evidence for DTNBP1 as genetic risk factor for schizophrenia.",
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T1 - Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations

AU - Li, T

AU - Zhang, F

AU - Liu, X

AU - Sun, X

AU - Sham, P C

AU - Crombie, C

AU - Ma, X

AU - Wang, Q

AU - Meng, H

AU - Deng, W

AU - Yates, P

AU - Hu, X

AU - Walker, N

AU - Murray, R M

AU - St Clair, D

AU - Collier, D A

PY - 2005

Y1 - 2005

N2 - The dystrobrevin-binding protein 1 (DTNBP1) gene on chromosome 6p has emerged as a potential susceptibility gene for schizophrenia. Although a number of attempts to replicate the original association finding have been successful, they have not identified any obvious pathogenic variants or a single at risk haplotype common to all populations studied. In the present study we attempted further replication in an independent sample of 638 nuclear families from the Han Chinese population of Sichuan Province, SW China. We also examined 580 Scottish schizophrenic cases and 620 controls. We genotyped 10 single-nucleotide polymorphisms ( SNPs) in DTNBP1 that were used in the original report of association, plus rs2619538 ( SNP 'A') in the putative promoter region, which has also been associated with schizophrenia. In the Chinese trios we found that two SNPs (P1635 and P1765) were significantly overtransmitted, but with alleles opposite to those reported in the original studies. SNPs P1757 and P1765 formed a common haplotype, which also showed significant overtransmission. In the Scottish cases and controls, no individual markers were significantly associated with schizophrenia. A single haplotype, which included rs2619538 and P1583, and one rare haplotype, composed of P1320 and P1757, were significantly associated with schizophrenia, but no previously reported haplotypes were associated. Based on the data from the Chinese population, our results provide statistical support for DTNBP1 as a susceptibility gene for schizophrenia, albeit with haplotypes different from those of the original study. However, our lack of replication in the Scottish samples also indicates that caution is warranted when evaluating the robustness of the evidence for DTNBP1 as genetic risk factor for schizophrenia.

AB - The dystrobrevin-binding protein 1 (DTNBP1) gene on chromosome 6p has emerged as a potential susceptibility gene for schizophrenia. Although a number of attempts to replicate the original association finding have been successful, they have not identified any obvious pathogenic variants or a single at risk haplotype common to all populations studied. In the present study we attempted further replication in an independent sample of 638 nuclear families from the Han Chinese population of Sichuan Province, SW China. We also examined 580 Scottish schizophrenic cases and 620 controls. We genotyped 10 single-nucleotide polymorphisms ( SNPs) in DTNBP1 that were used in the original report of association, plus rs2619538 ( SNP 'A') in the putative promoter region, which has also been associated with schizophrenia. In the Chinese trios we found that two SNPs (P1635 and P1765) were significantly overtransmitted, but with alleles opposite to those reported in the original studies. SNPs P1757 and P1765 formed a common haplotype, which also showed significant overtransmission. In the Scottish cases and controls, no individual markers were significantly associated with schizophrenia. A single haplotype, which included rs2619538 and P1583, and one rare haplotype, composed of P1320 and P1757, were significantly associated with schizophrenia, but no previously reported haplotypes were associated. Based on the data from the Chinese population, our results provide statistical support for DTNBP1 as a susceptibility gene for schizophrenia, albeit with haplotypes different from those of the original study. However, our lack of replication in the Scottish samples also indicates that caution is warranted when evaluating the robustness of the evidence for DTNBP1 as genetic risk factor for schizophrenia.

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KW - association

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KW - dysbindin

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KW - LINKAGE-DISEQUILIBRIUM

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KW - BIPOLAR DISORDER

KW - 6P22.3 GENE

KW - ASSOCIATION

KW - COMPLEX

KW - IDENTIFICATION

KW - METAANALYSIS

KW - BIOGENESIS

KW - EXPRESSION

U2 - 10.1038/sj.mp.4001718

DO - 10.1038/sj.mp.4001718

M3 - Article

VL - 10

SP - 1037

EP - 1044

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

ER -