In:
Psychiatric Genetics, Ovid Technologies (Wolters Kluwer Health)
Abstract:
Numerous genome-wide association studies have identified CACNA1C as one of the top risk genes for schizophrenia. As a necessary post-genome-wide association study (GWAS) follow-up, here, we focused on this risk gene, carefully investigated its novel risk variants for schizophrenia, and explored their potential functions. Methods We analyzed four independent samples (including three European and one African-American) comprising 5648 cases and 6936 healthy subjects to identify replicable single nucleotide polymorphism-schizophrenia associations. The potential regulatory effects of schizophrenia-risk alleles on CACNA1C mRNA expression in 16 brain regions ( n = 348), gray matter volumes (GMVs) of five subcortical structures ( n = 34 431), and surface areas and thickness of 34 cortical regions ( n = 36 936) were also examined. Results A novel 17-variant block across introns 36–45 of CACNA1C was significantly associated with schizophrenia in the same effect direction across at least two independent samples (1.8 × 10 −4 ≤ P ≤ 0.049). Most risk variants within this block showed significant associations with CACNA1C mRNA expression (1.6 × 10 −3 ≤ P ≤ 0.050), GMVs of subcortical structures (0.016 ≤ P ≤ 0.048), cortical surface areas (0.010 ≤ P ≤ 0.050), and thickness (0.004 ≤ P ≤ 0.050) in multiple brain regions. Conclusion We have identified a novel and functional risk variant block at CACNA1C for schizophrenia, providing further evidence for the important role of this gene in the pathogenesis of schizophrenia.
Type of Medium:
Online Resource
ISSN:
0955-8829
DOI:
10.1097/YPG.0000000000000344
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2023
detail.hit.zdb_id:
2063156-X
