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

A.R. Sanders, I. Rusu, J. Duan, J.E. Vander Molen, C. Hou, Sibylle Schwab, Dieter Wildenauer, M. Martinez, P.V. Gejman

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

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(108/158)Met. 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 30 portions of COMT and ARVCF, including Val(108/158)Met with Val(108/158) being the overtransmitted allele, consistent with previous studies. We also find Val(108/158)Met 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.
Original languageEnglish
Pages (from-to)1-13
JournalMolecular Psychiatry
Volume10
DOIs
Publication statusPublished - 2005

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