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Haplotypic association spanning the 22q11.21 genes COMT and ARVCF with schizophrenia

Journal Article


Abstract


  • Catechol-O-methyltransferase (COMT) has been implicated in schizophrenia by its function through its roles in monoamine neurotransmitter metabolism and its impact on prefrontal cognition, and also by its position through linkage scans and a strong cytogenetic association. Further support comes from association studies, especially family-based ones examining the COMT variant, Val 108/158Met. We have studied eight markers spanning COMT and including portions of the two immediately adjacent genes, thioredoxin reductase 2 and armadillo repeat deleted in velocardiofacial syndrome (ARVCF), using association testing in 136 schizophrenia families. We found nominal evidence for association of illness to rs165849 (P = 0.051) in ARVCF, and a stronger signal (global P = 0.0019-0.0036) from three-marker haplotypes spanning the 3��� portions of COMT and ARVCF, including Val108/158Met with Val 108/158 being the overtransmitted allele, consistent with previous studies. We also find Val108/158Met to be in linkage disequilibrium with the markers in ARVCF. These findings support previous association signals of schizophrenia to COMT markers, and suggest that ARVCF might contribute to this signal. ARVCF, a member of the catenin family, besides being a positional candidate, is also one due to its function, that is, its potential role in neurodevelopment, which is implicated in schizophrenia pathogenesis by several lines of evidence. �� 2005 Nature Publishing Group All rights reserved.

Publication Date


  • 2005

Citation


  • Sanders, A. R., Rusu, I., Duan, J., Vander Molen, J. E., Hou, C., Schwab, S. G., . . . Gejman, P. V. (2005). Haplotypic association spanning the 22q11.21 genes COMT and ARVCF with schizophrenia. Molecular Psychiatry, 10(4), 353-365. doi:10.1038/sj.mp.4001586

Scopus Eid


  • 2-s2.0-16844366262

Web Of Science Accession Number


Start Page


  • 353

End Page


  • 365

Volume


  • 10

Issue


  • 4

Place Of Publication


Abstract


  • Catechol-O-methyltransferase (COMT) has been implicated in schizophrenia by its function through its roles in monoamine neurotransmitter metabolism and its impact on prefrontal cognition, and also by its position through linkage scans and a strong cytogenetic association. Further support comes from association studies, especially family-based ones examining the COMT variant, Val 108/158Met. We have studied eight markers spanning COMT and including portions of the two immediately adjacent genes, thioredoxin reductase 2 and armadillo repeat deleted in velocardiofacial syndrome (ARVCF), using association testing in 136 schizophrenia families. We found nominal evidence for association of illness to rs165849 (P = 0.051) in ARVCF, and a stronger signal (global P = 0.0019-0.0036) from three-marker haplotypes spanning the 3��� portions of COMT and ARVCF, including Val108/158Met with Val 108/158 being the overtransmitted allele, consistent with previous studies. We also find Val108/158Met to be in linkage disequilibrium with the markers in ARVCF. These findings support previous association signals of schizophrenia to COMT markers, and suggest that ARVCF might contribute to this signal. ARVCF, a member of the catenin family, besides being a positional candidate, is also one due to its function, that is, its potential role in neurodevelopment, which is implicated in schizophrenia pathogenesis by several lines of evidence. �� 2005 Nature Publishing Group All rights reserved.

Publication Date


  • 2005

Citation


  • Sanders, A. R., Rusu, I., Duan, J., Vander Molen, J. E., Hou, C., Schwab, S. G., . . . Gejman, P. V. (2005). Haplotypic association spanning the 22q11.21 genes COMT and ARVCF with schizophrenia. Molecular Psychiatry, 10(4), 353-365. doi:10.1038/sj.mp.4001586

Scopus Eid


  • 2-s2.0-16844366262

Web Of Science Accession Number


Start Page


  • 353

End Page


  • 365

Volume


  • 10

Issue


  • 4

Place Of Publication