Duplications in RB1CC1 are associated with schizophrenia; identification in large European sample sets

Area of Science:

• Genetics
• Neuroscience
• Genomic Medicine

Background:

• Schizophrenia (SCZ) is a severe neuropsychiatric disorder with high heritability.
• De novo mutations identified by next-generation sequencing (NGS) are implicated in SCZ risk.
• Identifying specific genes involved in SCZ pathogenesis remains challenging.

Purpose of the Study:

• To investigate the role of copy number variations (CNVs) in SCZ risk.
• To screen candidate genes identified by NGS for recurrent CNVs.
• To determine if CNVs in specific genes are associated with SCZ.

Main Methods:

• Utilized genome-wide single-nucleotide polymorphism data to identify deletions and duplications (CNVs).
• Screened 55 candidate genes implicated by NGS studies in 1637 SCZ patients and 1627 controls.
• Validated findings in independent European cohorts, totaling 8461 patients and 112,871 controls.

Main Results:

• Duplications in the RB1CC1 gene were found to be significantly overrepresented in SCZ patients during the discovery phase.
• Combined analysis confirmed an association between RB1CC1 duplications and SCZ (P=1.29 × 10(-5); OR=8.58).
• This indicates rare duplications in RB1CC1 as a risk factor for schizophrenia.

Conclusions:

• Rare duplications in the RB1CC1 gene represent a significant risk factor for schizophrenia.
• CNV analysis is a valuable approach for identifying genetic contributors to complex disorders like SCZ.
• RB1CC1 warrants further investigation for its role in SCZ pathogenesis.