Linkage and association on 8p21.2-p21.1 in schizophrenia

M. Daniele Fallin, Virginia K. Lasseter, Yaping Liu, Dimitrios Avramopoulos, John McGrath, Paula S. Wolyniec, Gerald Nestadt, Kung Yee Liang, Pei Lung Chen, David Valle, Ann E. Pulver

Research output: Contribution to journalArticle

Abstract

In the past decade, we and others have consistently reported linkage to a schizophrenia (SZ) susceptibility region on chromosome 8p21. Most recently, in the largest SZ linkage sample to date, a multi-site international collaboration performed a SNP-based linkage scan (∼6,000 SNPs; 831 pedigrees; 121 from Johns Hopkins (JHU)), that showed the strongest evidence for linkage in a 1Mb region of chr 8p21 from rs1561817 to rs9797 (Zmax=3.22, P=0.0004) [Holmans et al. 2009. Mol Psychiatry]. We have investigated this 8p21 peak region further in two ways: first by linkage and family-based association in 106 8p-linked European-Caucasian (EUC) JHU pedigrees using 1,402 SNPs across a 4.4Mb region surrounding the peak; second, by an independent case-control association study in the genetically more homogeneous Ashkenazim (AJ) (709 cases, 1,547 controls) using 970 SNPs in a further narrowed 2.8Mb region. Family-based association analyses in EUC pedigrees and case-control analyses in AJ samples reveal significant associations for SNPs in and around DPYSL2 and ADRA1A, candidate genes previously associated with SZ in our work and others. Further, several independent gene expression studies have shown that DPYSL2 is differentially expressed in SZ brains [Beasley et al. 2006. Proteomics 6(11):3414-3425; Edgar et al. 2000. Mol Psychiatry 5(1):85-90; Johnston-Wilson et al. 2000. Mol Psychiatry 5(2):142-149] or in response to psychosis-inducing pharmaceuticals [Iwazaki et al. 2007. Proteomics 7(7):1131-1139; Paulson et al. 2004. Proteomics 4(3):819-825]. Taken together, this work further supports DPYSL2 and the surrounding genomic region as a susceptibility locus for SZ.

Original languageEnglish (US)
Pages (from-to)188-197
Number of pages10
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume156
Issue number2
DOIs
StatePublished - Mar 1 2011

Keywords

  • Association
  • Chromosome 8
  • DPYSL2
  • Schizophrenia

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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