Evidence for transmission disequilibrium at the DAOA gene locus in a schizophrenia family sample

Ma, Jianhua; Sun, Jian; Zhang, Huan; Zhang, Rui; Kang, Wan Hu; Gao, Cheng; Liu, Hai Sheng; Xue, Hong; Min, Zi Xin; Zhao, Wen Xiang; Ning, Qi Lan; Wang, Shu Hong; Zhang, Yin Cang; Guo, Ting; Lu, She Min

doi:10.1016/j.neulet.2009.06.070

Cited by 11 publications

(5 citation statements)

References 37 publications

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“…The authors of this study conclude that gray matter atrophy in the left insula might be more a feature of schizophrenia, while changes in the right insula might be linked to psychotic features in both schizophrenia and bipolar disorder. Given that genetic variation at G72 has been repeatedly reported to be associated with schizophrenia [6][7][8][9][10] as well as with bipolar disorder [10,11], it is tempting to speculate that the observed fiber tract changes might contribute to a neuroanatomic endophenotype that contributes to both disorders. However, it needs to be pointed out that further studies are needed to corroborate this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic variation at G72 has been repeatedly reported to be associated with schizophrenia [6][7][8][9][10] as well as with other psychiatric disorders, i.e., bipolar disorder [10,11], major depression [12] and panic disorder [13]. Furthermore, a variant at the G72 locus has been among the top findings (p = 1.23 9 10 -7 ) in a recent meta-analysis of GWAS of schizophrenia and bipolar disorder [14].…”

Section: Introductionmentioning

confidence: 99%

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Genetic variation in the G72 gene is associated with increased frontotemporal fiber tract integrity

Nickl‐Jockschat

Stöcker

Krug

et al. 2014

Eur Arch Psychiatry Clin Neurosci

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G72 (syn. DAOA, D-amino acid oxidase activator) is a susceptibility gene for both schizophrenia and bipolar disorder. Diffusion tensor imaging studies hint at changes in fiber tract integrity in both disorders. We aimed to investigate whether a G72 susceptibility haplotype causes changes in fiber tract integrity in young healthy subjects. We compared fractional anisotropy in 47 subjects that were either homozygous for the M23/M24 risk haplotype (n = 20) or homozygous for M23(rs3918342)/M24(rs1421292) wild type (n = 27) using diffusion tensor imaging with 3 T. Tract-based spatial statistics, a method especially developed for diffusion data analysis, was used to delineate the major fiber tracts. We found clusters of increased FA values in homozygous risk haplotype carriers in the right periinsular region and in the right inferior parietal lobe (IPL). We did not find clusters indicating decreased FA values. The insula and the IPL have been implicated in both schizophrenia and bipolar pathophysiology. Increased FA values might reflect changes in dendritic morphology as previously described by in vitro studies. These findings further corroborate the hypothesis that a shared gene pool between schizophrenia and bipolar disorder might lead to neuroanatomic changes that confer an unspecific vulnerability for both disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic variation in the G72 gene is associated with increased frontotemporal fiber tract integrity

Nickl‐Jockschat

Stöcker

Krug

et al. 2014

Eur Arch Psychiatry Clin Neurosci

View full text Add to dashboard Cite

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“…The association of neurological disorders and G72 gene variations was first discovered in schizophrenia and psychiatric conditions [153][154][155][156]. In the paper reporting the discovery of the G72 gene, Chumakov et al suggested a possible link between pLG72 and schizophrenia due to its DAAO modulation function [138].…”

Section: Role Of G72 In Schizophreniamentioning

confidence: 99%

d-Amino Acids and pLG72 in Alzheimer’s Disease and Schizophrenia

Cheng

Lin

Lane

2021

IJMS

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Numerous studies over the last several years have shown that d-amino acids, especially d-serine, have been related to brain and neurological disorders. Acknowledged neurological functions of d-amino acids include neurotransmission and learning and memory functions through modulating N-methyl-d-aspartate type glutamate receptors (NMDARs). Aberrant d-amino acids level and polymorphisms of genes related to d-amino acids metabolism are associated with neurodegenerative brain conditions. This review summarizes the roles of d-amino acids and pLG72, also known as d-amino acid oxidase activator, on two neurodegenerative disorders, schizophrenia and Alzheimer’s disease (AD). The scope includes the changes in d-amino acids levels, gene polymorphisms of G72 genomics, and the role of pLG72 on NMDARs and mitochondria in schizophrenia and AD. The clinical diagnostic value of d-amino acids and pLG72 and the therapeutic importance are also reviewed.

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“…The DAOA gene locus on chromosome 13q32‐q34 has been implicated in the etiology of SCZ. Three SNPs (rs778294, rs779293, and rs3918342) have been identified in this region, and two of them (rs778293 and rs3918342) have shown significant transmission disequilibrium and a highly significant under‐transmission between haplotype CAT and SCZ [46]. G72 is one of the most widely tested genes for association with SCZ.…”

Section: Structural Genomicsmentioning

confidence: 99%

Genomics and Pharmacogenomics of Schizophrenia

Cacabelos

Martínez-Bouza

2010

CNS Neuroscience & Therapeutics

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Schizophrenia (SCZ) is among the most disabling of mental disorders. Several neurobiological hypotheses have been postulated as responsible for SCZ pathogenesis: polygenic/multifactorial genomic defects, intrauterine and perinatal environment-genome interactions, neurodevelopmental defects, dopaminergic, cholinergic, serotonergic, gamma-aminobutiric acid (GABAergic), neuropeptidergic and glutamatergic/N-Methyl-D-Aspartate (NMDA) dysfunctions, seasonal infection, neuroimmune dysfunction, and epigenetic dysregulation. SCZ has a heritability estimated at 60-90%. Genetic studies in SCZ have revealed the presence of chromosome anomalies, copy number variants, multiple single-nucleotide polymorphisms of susceptibility distributed across the human genome, aberrant single nucleotide polymorphisms (SNPs) in microRNA genes, mitochondrial DNA mutations, and epigenetic phenomena. Pharmacogenetic studies of psychotropic drug response have focused on determining the relationship between variation in specific candidate genes and the positive and adverse effects of drug treatment. Approximately, 18% of neuroleptics are major substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4; 24% of antidepressants are major substrates of CYP1A2 enzymes, 5% of CYP2B6, 38% of CYP2C19, 85% of CYP2D6, and 38% of CYP3A4; 7% of benzodiazepines are major substrates of CYP2C19 enzymes, 20% of CYP2D6, and 95% of CYP3A4. About 10-20% of Western populations are defective in genes of the CYP superfamily. Only 26% of Southern Europeans are pure extensive metabolizers for the trigenic cluster integrated by the CYP2D6+CYP2C19+CYP2C9 genes. The pharmacogenomic response of SCZ patients to conventional psychotropic drugs also depends on genetic variants associated with SCZ-related genes. Consequently, the incorporation of pharmacogenomic procedures both to drugs in development and drugs on the market would help to optimize therapeutics in SCZ and other central nervous system (CNS) disorders.

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Evidence for transmission disequilibrium at the DAOA gene locus in a schizophrenia family sample

Cited by 11 publications

References 37 publications

Genetic variation in the G72 gene is associated with increased frontotemporal fiber tract integrity

Genetic variation in the G72 gene is associated with increased frontotemporal fiber tract integrity

d-Amino Acids and pLG72 in Alzheimer’s Disease and Schizophrenia

Genomics and Pharmacogenomics of Schizophrenia

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