Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0036341 (
schizophrenia
)
60,220
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Background
: Prepulse inhibition (PPI) of the startle response is a highly conserved form of sensorimotor gating, disruption of which is found in
schizophrenia
patients and their unaffected first-degree relatives. PPI can be measured in many species, and shows considerable phenotypic variation between and within rodent models. This makes PPI a useful endophenotype. Genome-wide association studies (GWAS) have been carried out to identify genetic variants underlying
schizophrenia
, and these suggest that
schizophrenia
is highly polygenic. GWAS have been unable to account for the high heritability of
schizophrenia
seen in family studies, partly because of the low power of GWAS due to multiple comparisons. By contrast, complementary mouse model linkage studies often have high statistical power to detect variants for behavioral traits but lower resolution, producing loci that include tens or hundreds of genes. To capitalize on the advantages of both GWAS and genetic mouse models, our study uses a cross-species approach to identify novel genes associated with PPI regulation, which thus may contribute to the PPI deficits seen in
schizophrenia
.
Results
: Using experimental data from the recombinant inbred (RI) mouse panel BXD, we identified two significant loci affecting PPI. These genomic regions contain genetic variants which influence PPI in mice and are therefore candidates that may be influencing aspects of
schizophrenia
in humans. We next investigated these regions in whole-genome data from the Psychiatric Genomics Consortium (PGC)
schizophrenia
GWAS and identify one novel candidate gene (
ABPP1IP
) that was significantly associated with PPI in mice and risk of
schizophrenia
in humans. A systems genetics approach demonstrates that
APBB1IP
coexpresses with several other genes related to
schizophrenia
in several brain regions. Gene coexpression and enrichment analysis shows clear links between
APBB1IP
and the immune system.
Conclusion
: The combination of human GWAS and mouse quantitative trait loci (QTL) from some of the largest study systems available has enabled us to identify a novel gene,
APBB1IP
, which influences
schizophrenia
in humans and PPI in mice.
...
PMID:A Cross-Species Systems Genetics Analysis Links APBB1IP as a Candidate for Schizophrenia and Prepulse Inhibition. 3192 May 76
