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

✍ Scribed by 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

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 426 KB
• Volume: 156
• Category: Article
• ISSN: 1552-4841
• DOI: 10.1002/ajmg.b.31154

✦ Synopsis

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 ¼ 3.22, P ¼ 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. Familybased 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 [