In:
Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 47, No. 4 ( 2021-07-08), p. 1190-1200
Abstract:
We previously identified quantitative trait loci (QTL) for prepulse inhibition (PPI), an endophenotype of schizophrenia, on mouse chromosome 10 and reported Fabp7 as a candidate gene from an analysis of F2 mice from inbred strains with high (C57BL/6N; B6) and low (C3H/HeN; C3H) PPI levels. Here, we reanalyzed the previously reported QTLs with increased marker density. The highest logarithm of odds score (26.66) peaked at a synonymous coding and splice-site variant, c.753G & gt;A (rs257098870), in the Cdh23 gene on chromosome 10; the c.753G (C3H) allele showed a PPI-lowering effect. Bayesian multiple QTL mapping also supported the same variant with a posterior probability of 1. Thus, we engineered the c.753G (C3H) allele into the B6 genetic background, which led to dampened PPI. We also revealed an e-QTL (expression QTL) effect imparted by the c.753G & gt;A variant for the Cdh23 expression in the brain. In a human study, a homologous variant (c.753G & gt;A; rs769896655) in CDH23 showed a nominally significant enrichment in individuals with schizophrenia. We also identified multiple potentially deleterious CDH23 variants in individuals with schizophrenia. Collectively, the present study reveals a PPI-regulating Cdh23 variant and a possible contribution of CDH23 to schizophrenia susceptibility.
Type of Medium:
Online Resource
ISSN:
0586-7614
,
1745-1701
DOI:
10.1093/schbul/sbab007
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2021
detail.hit.zdb_id:
2180196-4
SSG:
15,3
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