title: 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.
authors.affiliation: Department of Evolution, Genomics and Systematics, Uppsala University, Uppsala, Sweden.
authors.forename: Karolina
authors.initials: K
authors.lastname: Aberg
authors.forename: Elin
authors.initials: E
authors.lastname: Axelsson
authors.forename: Peter
authors.initials: P
authors.lastname: Saetre
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.forename: Lennart
authors.initials: L
authors.lastname: Wetterberg
authors.forename: Ulf
authors.initials: U
authors.lastname: Pettersson
authors.forename: Eva
authors.initials: E
authors.lastname: Lindholm
authors.forename: Elena
authors.initials: E
authors.lastname: Jazin
mesh_terms: D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5; D002898:Chromosomes, Human, Pair 8; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology