Support for schizophrenia susceptibility locus on chromosome 2q detected in a Swedish isolate using a dense map of microsatellites and SNPs

Abstract

Extended pedigrees are not only very useful to identify disease genes for rare Mendelian conditions, but they may also help unravel the genetics of complex diseases such as schizophrenia. In this study we performed genome-wide multipoint non-parametric linkage (NPL) score calculations using 825 microsatellites and 5,366 single nucleotide polymorphisms (SNPs), respectively, and searched for haplotypes shared by affected individuals, in three multiplex families including 29 genotyped affected individuals which in total contains 49 relative pairs useful for linkage studies. The most consistent results for microsatellites and SNPs were observed on 2q12.3-q14.1 (NPL scores 2.0, empirical P-value 0.009). However, the overall highest NPL score was observed on chromosome 2q33.3 using SNPs (NPL score 2.2, empirical P-value 0.007). Other chromosomal regions were detected on 5q15-q22.1, with microsatellites (NPL scores 1.7, empirical P-value 0.021) and with SNPs (NPL scores 2.0, empirical P-value 0.010) and on 5q23.1 (NPL score 1.9, empirical P-value 0.012) and 8q24.1-q24.2 (NPL score 2.1, empirical P-value 0.009) when using SNPs. The analysis of extended pedigrees allowed the search for haplotypes inherited identical by decent (IBD) by affected individuals. In all regions with NPL score >1.9 we found haplotypes inherited IBD by multiple cases. However, no common haplotypes were found for affected individuals in all families. In conclusion our NPL results support earlier findings suggesting that 2q and possibly 5q and 8q contain susceptibility loci for schizophrenia. Haplotype sharing in families helped to delimit the detected regions that potentially are susceptibility loci for schizophrenia.

Genome‐wide association analysis of age at onset in schizophrenia in a European‐American sample

“…This gene is associated with increased risk for autoimmune thyroid disease [Shirasawa et al, 2004], multiple sclerosis [Comabella et al, 2009], and adult height [Takeuchi et al, 2009]. Additionally, linkage analyses has provided compelling evidence for the existence in the 8q24 region for the pathogenesis of bipolar disorder [Park et al, 2004] and SCZ [Walss-Bass et al, 2006;Aberg et al, 2008;Holmans et al, 2009]. Interestingly, suggestive linkages at 8p21.3 and 8q12.1 for AAO of SCZ have been reported [Fanous et al, 2007].…”

Proteomic Identification of Binding Partners for the Brain Metabolite Lanthionine Ketimine (LK) and Documentation of LK Effects on Microglia and Motoneuron Cell Cultures

“…The genomic region of human chromosome 2q34 proximal to LanCL1 has been implicated in early-onset AD susceptibility (Scott et al 2003); forms of familial schizophrenia (Aberg et al 2008); and neural tube defects (Stamm et al 2008). Several prior, separate associations of schizophrenia with CRMP2, STXBP1, and the LanCL1-containing region of chromosome 2q34 offer an intriguing coincidence amongst these three candidate LK-binding proteins that is worthy of further inquiry.…”

Evaluation of an antimicrobial silver foam dressing for use with V.A.C.® therapy: Morphological, mechanical, and antimicrobial properties

“…This gene is associated with increased risk for autoimmune thyroid disease [Shirasawa et al, 2004], multiple sclerosis [Comabella et al, 2009], and adult height [Takeuchi et al, 2009]. Additionally, linkage analyses has provided compelling evidence for the existence in the 8q24 region for the pathogenesis of bipolar disorder [Park et al, 2004] and SCZ [Walss‐Bass et al, 2006; Aberg et al, 2008; Holmans et al, 2009]. Interestingly, suggestive linkages at 8p21.3 and 8q12.1 for AAO of SCZ have been reported [Fanous et al, 2007].…”