The TGM2 gene is associated with schizophrenia in a British population

Matilda Bradford, Matthew H Law, Andrew D Stewart, Duncan J Shaw, Ian L Megson, Jun Wei

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Several lines of evidence have suggested an interesting link between gluten ingestion and schizophrenia. Increased levels of gliadin antibodies have been observed in patients with schizophrenia. Tissue transglutaminase (transglutaminase 2, TGM2) is involved in the production of gliadin antibodies. To investigate genetic association of the TGM2 gene with schizophrenia, we detected eight single nucleotide polymorphisms (SNPs) present in the gene among 131 family trios composed of fathers, mothers and affected offspring with schizophrenia. Data analysis with the UNPHASED program showed allelic association for rs2076380 (chi(2) = 5.51, P = 0.019), rs7270785 (chi(2) = 8.13, P = 0.004), rs4811528 (chi(2) = 6.13, P = 0.013) and rs6023526 (chi(2) = 6.13, P = 0.013). The global P-value was 0.029 for 10,000 permutations with the TDT analysis. The strongest association was observed for the rs7270785-rs4811528 haplotypes (chi(2) = 16.18, df = 3, P = 0.001), and the global P-value was 0.008 for 10,000 permutations with the 2-SNP haplotype analysis. The 8-SNP haplotype analysis also revealed a strong haplotypic association (chi(2) = 44.82, df = 18, P = 0.0004) and the 1-df test showed that the A-T-A-A-T-G-A-G haplotype was excessively transmitted (chi(2) = 16.98, corrected P = 0.0007). The present results suggest that the TGM2 gene may be involved in the development of schizophrenia.
Original languageEnglish
Pages (from-to)335-340
Number of pages6
JournalAmerican Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Volume150B
Issue number3
Early online date16 Jun 2008
DOIs
Publication statusPublished - 5 Apr 2009

Fingerprint

Schizophrenia
Haplotypes
Single Nucleotide Polymorphism
Gliadin
Population
Genes
Glutens
Fathers
Antibody Formation
Eating
Mothers
transglutaminase 2
Antibodies

Keywords

  • alleles
  • GTP-binding proteins
  • gene frequency
  • genetic predisposition to disease
  • genetics, population
  • Great Britain
  • haplotypes
  • humans
  • linkage disequilibrium
  • nuclear family
  • polymorphism, single nucleotide
  • population groups
  • schizophrenia
  • transglutaminases
  • tissue transglutaminase
  • association study
  • genetic variation
  • gluten

Cite this

The TGM2 gene is associated with schizophrenia in a British population. / Bradford, Matilda; Law, Matthew H; Stewart, Andrew D; Shaw, Duncan J; Megson, Ian L; Wei, Jun.

In: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, Vol. 150B, No. 3, 05.04.2009, p. 335-340.

Research output: Contribution to journalArticle

Bradford, Matilda ; Law, Matthew H ; Stewart, Andrew D ; Shaw, Duncan J ; Megson, Ian L ; Wei, Jun. / The TGM2 gene is associated with schizophrenia in a British population. In: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 2009 ; Vol. 150B, No. 3. pp. 335-340.
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abstract = "Several lines of evidence have suggested an interesting link between gluten ingestion and schizophrenia. Increased levels of gliadin antibodies have been observed in patients with schizophrenia. Tissue transglutaminase (transglutaminase 2, TGM2) is involved in the production of gliadin antibodies. To investigate genetic association of the TGM2 gene with schizophrenia, we detected eight single nucleotide polymorphisms (SNPs) present in the gene among 131 family trios composed of fathers, mothers and affected offspring with schizophrenia. Data analysis with the UNPHASED program showed allelic association for rs2076380 (chi(2) = 5.51, P = 0.019), rs7270785 (chi(2) = 8.13, P = 0.004), rs4811528 (chi(2) = 6.13, P = 0.013) and rs6023526 (chi(2) = 6.13, P = 0.013). The global P-value was 0.029 for 10,000 permutations with the TDT analysis. The strongest association was observed for the rs7270785-rs4811528 haplotypes (chi(2) = 16.18, df = 3, P = 0.001), and the global P-value was 0.008 for 10,000 permutations with the 2-SNP haplotype analysis. The 8-SNP haplotype analysis also revealed a strong haplotypic association (chi(2) = 44.82, df = 18, P = 0.0004) and the 1-df test showed that the A-T-A-A-T-G-A-G haplotype was excessively transmitted (chi(2) = 16.98, corrected P = 0.0007). The present results suggest that the TGM2 gene may be involved in the development of schizophrenia.",
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T1 - The TGM2 gene is associated with schizophrenia in a British population

AU - Bradford, Matilda

AU - Law, Matthew H

AU - Stewart, Andrew D

AU - Shaw, Duncan J

AU - Megson, Ian L

AU - Wei, Jun

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N2 - Several lines of evidence have suggested an interesting link between gluten ingestion and schizophrenia. Increased levels of gliadin antibodies have been observed in patients with schizophrenia. Tissue transglutaminase (transglutaminase 2, TGM2) is involved in the production of gliadin antibodies. To investigate genetic association of the TGM2 gene with schizophrenia, we detected eight single nucleotide polymorphisms (SNPs) present in the gene among 131 family trios composed of fathers, mothers and affected offspring with schizophrenia. Data analysis with the UNPHASED program showed allelic association for rs2076380 (chi(2) = 5.51, P = 0.019), rs7270785 (chi(2) = 8.13, P = 0.004), rs4811528 (chi(2) = 6.13, P = 0.013) and rs6023526 (chi(2) = 6.13, P = 0.013). The global P-value was 0.029 for 10,000 permutations with the TDT analysis. The strongest association was observed for the rs7270785-rs4811528 haplotypes (chi(2) = 16.18, df = 3, P = 0.001), and the global P-value was 0.008 for 10,000 permutations with the 2-SNP haplotype analysis. The 8-SNP haplotype analysis also revealed a strong haplotypic association (chi(2) = 44.82, df = 18, P = 0.0004) and the 1-df test showed that the A-T-A-A-T-G-A-G haplotype was excessively transmitted (chi(2) = 16.98, corrected P = 0.0007). The present results suggest that the TGM2 gene may be involved in the development of schizophrenia.

AB - Several lines of evidence have suggested an interesting link between gluten ingestion and schizophrenia. Increased levels of gliadin antibodies have been observed in patients with schizophrenia. Tissue transglutaminase (transglutaminase 2, TGM2) is involved in the production of gliadin antibodies. To investigate genetic association of the TGM2 gene with schizophrenia, we detected eight single nucleotide polymorphisms (SNPs) present in the gene among 131 family trios composed of fathers, mothers and affected offspring with schizophrenia. Data analysis with the UNPHASED program showed allelic association for rs2076380 (chi(2) = 5.51, P = 0.019), rs7270785 (chi(2) = 8.13, P = 0.004), rs4811528 (chi(2) = 6.13, P = 0.013) and rs6023526 (chi(2) = 6.13, P = 0.013). The global P-value was 0.029 for 10,000 permutations with the TDT analysis. The strongest association was observed for the rs7270785-rs4811528 haplotypes (chi(2) = 16.18, df = 3, P = 0.001), and the global P-value was 0.008 for 10,000 permutations with the 2-SNP haplotype analysis. The 8-SNP haplotype analysis also revealed a strong haplotypic association (chi(2) = 44.82, df = 18, P = 0.0004) and the 1-df test showed that the A-T-A-A-T-G-A-G haplotype was excessively transmitted (chi(2) = 16.98, corrected P = 0.0007). The present results suggest that the TGM2 gene may be involved in the development of schizophrenia.

KW - alleles

KW - GTP-binding proteins

KW - gene frequency

KW - genetic predisposition to disease

KW - genetics, population

KW - Great Britain

KW - haplotypes

KW - humans

KW - linkage disequilibrium

KW - nuclear family

KW - polymorphism, single nucleotide

KW - population groups

KW - schizophrenia

KW - transglutaminases

KW - tissue transglutaminase

KW - association study

KW - genetic variation

KW - gluten

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DO - 10.1002/ajmg.b.30813

M3 - Article

VL - 150B

SP - 335

EP - 340

JO - American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics

SN - 1552-4841

IS - 3

ER -