Investigation of the apolipoprotein-L (APOL) gene family and schizophrenia using a novel DNA pooling strategy for public database SNPs.
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.
McGhee
Kevin A
KA
Neuropsychiatric Genetics Group, Institute of Molecular Medicine, Trinity College Dublin, St. James Hospital, James Street, Dublin 8, Ireland.
Morris
Derek W
DW
Schwaiger
Siobhan
S
Nangle
Jeanne-Marie
JM
Donohoe
Gary
G
Clarke
Sarah
S
Meagher
David
D
Quinn
John
J
Scully
Paul
P
Waddington
John L
JL
Gill
Michael
M
Corvin
Aiden
A
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
C108666:APOL1 protein, human; C502578:ApoL6, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D000075943:Apolipoproteins L; D005819:Genetic Markers; D008075:Lipoproteins, HDL; D004247:DNA