title: Investigation of the apolipoprotein-L (APOL) gene family and schizophrenia using a novel DNA pooling strategy for public database SNPs.
abstract: We performed an extensive genetic association study of the six known apolipoprotein-L (APOL) genes and schizophrenia (SZ) using a novel DNA pooling strategy. The APOL genes are both positional and functional candidate genes for SZ. This gene family maps to chromosome 22q12.3, a region implicated by SZ linkage studies as likely to contain one or more SZ susceptibility genes. A recent gene expression study demonstrated up-regulation of APOL1, 2, and 4 in post-mortem brain samples from SZ patients compared to controls in two independent samples. To test for genetic association with SZ, we analyzed 143 SNPs from dbSNP from across the APOL genes in an Irish sample of 219 cases and 231 controls. Of these 143 SNPs, 51 (36%) were polymorphic in our Irish sample and were genotyped using a novel three-stage DNA pooling strategy. This strategy does not require the identification of a heterozygous individual for DNA pooling association analysis and is therefore very efficient when using public database SNPs. We found no evidence to support the hypothesis that genetic variation at the APOL genes contributes to SZ susceptibility in our sample.
authors.affiliation: Neuropsychiatric Genetics Group, Institute of Molecular Medicine, Trinity College Dublin, St. James Hospital, James Street, Dublin 8, Ireland.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: McGhee
authors.forename: Derek W
authors.initials: DW
authors.lastname: Morris
authors.forename: Siobhan
authors.initials: S
authors.lastname: Schwaiger
authors.forename: Jeanne-Marie
authors.initials: JM
authors.lastname: Nangle
authors.forename: Gary
authors.initials: G
authors.lastname: Donohoe
authors.forename: Sarah
authors.initials: S
authors.lastname: Clarke
authors.forename: David
authors.initials: D
authors.lastname: Meagher
authors.forename: John
authors.initials: J
authors.lastname: Quinn
authors.forename: Paul
authors.initials: P
authors.lastname: Scully
authors.forename: John L
authors.initials: JL
authors.lastname: Waddington
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Aiden
authors.initials: A
authors.lastname: Corvin
mesh_terms: D000483:Alleles; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D000075943:Apolipoproteins L; D016022:Case-Control Studies; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D004247:DNA / Q000235:genetics*; D030541:Databases, Genetic; D005788:Gene Pool; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C108666:APOL1 protein, human; C502578:ApoL6, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D000075943:Apolipoproteins L; D005819:Genetic Markers; D008075:Lipoproteins, HDL; D004247:DNA