| 1 | PLoS ONE 2009 -1 4: e5246 |
|---|---|
| PMID | 19370154 |
| Title | In silico whole genome association scan for murine prepulse inhibition. |
| Abstract | The complex trait of prepulse inhibition (PPI) is a sensory gating measure related toschizophreniaand can be measured in mice. Large-scale public repositories of inbred mouse strain genotypes and phenotypes such as PPI can be used to detect Quantitative Trait Loci (QTLs) in silico. However, the method has been criticized for issues including insufficient number of strains, not controlling for false discoveries, the complex haplotype structure of inbred mice, and failing to account for genotypic and phenotypic subgroups. 我们实现了一个解决方法es these issues by incorporating phylogenetic analyses, multilevel regression with mixed effects, and false discovery rate (FDR) control. A genome-wide scan for PPI was conducted using over 17,000 single nucleotide polymorphisms (SNPs) in 37 strains phenotyped. Eighty-nine SNPs were significant at a false discovery rate (FDR) of 5%. After accounting for long-range linkage disequilibrium, we found 3 independent QTLs located on murine chromosomes 1 and 13. One of the PPI positives corresponds to a region of human chromosome 6p which includes DTNBP1, a gene implicated inschizophrenia. Another region includes the geneTSNwhich alters PPI when knocked out. These genes also appear to have correlated expression with PPI. These results support the usefulness of using an improved in silico mapping method to identify QTLs for complex traits such as PPI which can be then be used for to help identify loci influencingschizophreniain humans. |
| SCZ Keywords | schizophrenia |