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Linkage and association on 8p21.2‐p21.1 in schizophrenia
Author(s) -
Fallin M. Daniele,
Lasseter Virginia K.,
Liu Yaping,
Avramopoulos Dimitrios,
McGrath John,
Wolyniec Paula S.,
Nestadt Gerald,
Liang KungYee,
Chen PeiLung,
Valle David,
Pulver Ann E.
Publication year - 2011
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.31154
Subject(s) - pedigree chart , single nucleotide polymorphism , linkage (software) , genetics , genetic association , genetic linkage , snp , biology , gene , psychology , genotype
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 1 Mb region of chr 8p21 from rs1561817 to rs9797 (Z max = 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 4.4 Mb 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 2.8 Mb 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. © 2010 Wiley‐Liss, Inc.