Association analysis of the RGS4 gene in Han Chinese and Scottish populations with schizophrenia

F  Zhang; D  St Clair; 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 A  Collier; T  Li

doi:10.1111/j.1601-183X.2005.00167.x

Association analysis of the RGS4 gene in Han Chinese and Scottish populations with schizophrenia

F Zhang, D St Clair, 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 A Collier, T Li

Applied Medicine

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Abstract

We investigated the RGS4 as a susceptibility gene for schizophrenia in Chinese Han (184 trios and 138 sibling pairs, a total of 322 families) and Scottish (580 cases and 620 controls) populations using both a family trio and case-control design. Both the samples had statistical power greater than 70% to detect a heterozygote genotype relative risk of >1.2 for frequent RGS4-risk alleles. We genotyped four single nucleotide polymorphisms (SNPs) which have previously been associated with schizophrenia as either individually or part of haplotypes. Allele frequencies and linkage disequilibrium between the SNPs was similar in the two populations. In the Chinese sample, no individual SNPs or any of their haplotypes were associated with schizophrenia. In the Scottish population, one SNP (SNP7) was significantly over-represented in the cases compared with the controls (0.44 vs. 0.38; A allele; chi(2) 7.08, P = 0.011 after correction for correlation between markers by permutation testing). One two-marker haplotype, composed of alleles T and A of SNP4 and SNP7, respectively, showed individual significance after correction by permutation testing (chi(2) 6.8; P = 0.04). None of the full four-marker haplotypes showed association, including the G-G-G-G haplotype previously associated with schizophrenia in more than one sample and the A-T-A-A haplotype. Thus, our data do not directly replicate previous associations of RGS4, but association with SNP 7 in the Scottish population provides some support for a role in schizophrenia susceptibility. We cannot conclusively exclude RGS4, as associated haplotypes are likely to be surrogates for unknown causative alleles, whose relationship with overlying haplotypes may differ between the population groups. Differences in the association seen across the two populations could result from methodological factors such as diagnostic differences but most likely result from ethnic differences in haplotype structures within RGS4.

Original language	English
Pages (from-to)	444-448
Number of pages	5
Journal	Genes, Brain, and Behavior
Volume	4
DOIs	https://doi.org/10.1111/j.1601-183X.2005.00167.x
Publication status	Published - 2005

Keywords

chromosome 1q
genetic susceptibility
psychosis
regulator of G protein signalling
BIPOLAR DISORDER
POLYMORPHISMS
METAANALYSIS
REGULATOR

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Zhang, F., St Clair, D., 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., Collier, D. A., & Li, T. (2005). Association analysis of the RGS4 gene in Han Chinese and Scottish populations with schizophrenia. Genes, Brain, and Behavior, 4, 444-448. https://doi.org/10.1111/j.1601-183X.2005.00167.x

@article{1290cc1c273a45688b7047dbeae24443,

title = "Association analysis of the RGS4 gene in Han Chinese and Scottish populations with schizophrenia",

abstract = "We investigated the RGS4 as a susceptibility gene for schizophrenia in Chinese Han (184 trios and 138 sibling pairs, a total of 322 families) and Scottish (580 cases and 620 controls) populations using both a family trio and case-control design. Both the samples had statistical power greater than 70% to detect a heterozygote genotype relative risk of >1.2 for frequent RGS4-risk alleles. We genotyped four single nucleotide polymorphisms (SNPs) which have previously been associated with schizophrenia as either individually or part of haplotypes. Allele frequencies and linkage disequilibrium between the SNPs was similar in the two populations. In the Chinese sample, no individual SNPs or any of their haplotypes were associated with schizophrenia. In the Scottish population, one SNP (SNP7) was significantly over-represented in the cases compared with the controls (0.44 vs. 0.38; A allele; chi(2) 7.08, P = 0.011 after correction for correlation between markers by permutation testing). One two-marker haplotype, composed of alleles T and A of SNP4 and SNP7, respectively, showed individual significance after correction by permutation testing (chi(2) 6.8; P = 0.04). None of the full four-marker haplotypes showed association, including the G-G-G-G haplotype previously associated with schizophrenia in more than one sample and the A-T-A-A haplotype. Thus, our data do not directly replicate previous associations of RGS4, but association with SNP 7 in the Scottish population provides some support for a role in schizophrenia susceptibility. We cannot conclusively exclude RGS4, as associated haplotypes are likely to be surrogates for unknown causative alleles, whose relationship with overlying haplotypes may differ between the population groups. Differences in the association seen across the two populations could result from methodological factors such as diagnostic differences but most likely result from ethnic differences in haplotype structures within RGS4.",

keywords = "chromosome 1q, genetic susceptibility, psychosis, regulator of G protein signalling, BIPOLAR DISORDER, POLYMORPHISMS, METAANALYSIS, REGULATOR",

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

year = "2005",

doi = "10.1111/j.1601-183X.2005.00167.x",

language = "English",

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pages = "444--448",

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TY - JOUR

T1 - Association analysis of the RGS4 gene in Han Chinese and Scottish populations with schizophrenia

AU - Zhang, F

AU - St Clair, D

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 - Collier, D A

AU - Li, T

PY - 2005

Y1 - 2005

N2 - We investigated the RGS4 as a susceptibility gene for schizophrenia in Chinese Han (184 trios and 138 sibling pairs, a total of 322 families) and Scottish (580 cases and 620 controls) populations using both a family trio and case-control design. Both the samples had statistical power greater than 70% to detect a heterozygote genotype relative risk of >1.2 for frequent RGS4-risk alleles. We genotyped four single nucleotide polymorphisms (SNPs) which have previously been associated with schizophrenia as either individually or part of haplotypes. Allele frequencies and linkage disequilibrium between the SNPs was similar in the two populations. In the Chinese sample, no individual SNPs or any of their haplotypes were associated with schizophrenia. In the Scottish population, one SNP (SNP7) was significantly over-represented in the cases compared with the controls (0.44 vs. 0.38; A allele; chi(2) 7.08, P = 0.011 after correction for correlation between markers by permutation testing). One two-marker haplotype, composed of alleles T and A of SNP4 and SNP7, respectively, showed individual significance after correction by permutation testing (chi(2) 6.8; P = 0.04). None of the full four-marker haplotypes showed association, including the G-G-G-G haplotype previously associated with schizophrenia in more than one sample and the A-T-A-A haplotype. Thus, our data do not directly replicate previous associations of RGS4, but association with SNP 7 in the Scottish population provides some support for a role in schizophrenia susceptibility. We cannot conclusively exclude RGS4, as associated haplotypes are likely to be surrogates for unknown causative alleles, whose relationship with overlying haplotypes may differ between the population groups. Differences in the association seen across the two populations could result from methodological factors such as diagnostic differences but most likely result from ethnic differences in haplotype structures within RGS4.

AB - We investigated the RGS4 as a susceptibility gene for schizophrenia in Chinese Han (184 trios and 138 sibling pairs, a total of 322 families) and Scottish (580 cases and 620 controls) populations using both a family trio and case-control design. Both the samples had statistical power greater than 70% to detect a heterozygote genotype relative risk of >1.2 for frequent RGS4-risk alleles. We genotyped four single nucleotide polymorphisms (SNPs) which have previously been associated with schizophrenia as either individually or part of haplotypes. Allele frequencies and linkage disequilibrium between the SNPs was similar in the two populations. In the Chinese sample, no individual SNPs or any of their haplotypes were associated with schizophrenia. In the Scottish population, one SNP (SNP7) was significantly over-represented in the cases compared with the controls (0.44 vs. 0.38; A allele; chi(2) 7.08, P = 0.011 after correction for correlation between markers by permutation testing). One two-marker haplotype, composed of alleles T and A of SNP4 and SNP7, respectively, showed individual significance after correction by permutation testing (chi(2) 6.8; P = 0.04). None of the full four-marker haplotypes showed association, including the G-G-G-G haplotype previously associated with schizophrenia in more than one sample and the A-T-A-A haplotype. Thus, our data do not directly replicate previous associations of RGS4, but association with SNP 7 in the Scottish population provides some support for a role in schizophrenia susceptibility. We cannot conclusively exclude RGS4, as associated haplotypes are likely to be surrogates for unknown causative alleles, whose relationship with overlying haplotypes may differ between the population groups. Differences in the association seen across the two populations could result from methodological factors such as diagnostic differences but most likely result from ethnic differences in haplotype structures within RGS4.

KW - chromosome 1q

KW - genetic susceptibility

KW - psychosis

KW - regulator of G protein signalling

KW - BIPOLAR DISORDER

KW - POLYMORPHISMS

KW - METAANALYSIS

KW - REGULATOR

U2 - 10.1111/j.1601-183X.2005.00167.x

DO - 10.1111/j.1601-183X.2005.00167.x

M3 - Article

SN - 1601-183X

VL - 4

SP - 444

EP - 448

JO - Genes, Brain, and Behavior

JF - Genes, Brain, and Behavior

ER -

Association analysis of the RGS4 gene in Han Chinese and Scottish populations with schizophrenia

Abstract

Keywords

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