Copy number variations in RNF216 and postsynaptic membrane-associated genes are associated with bipolar disorder: a...

Area of Science:

• Genetics
• Neuroscience
• Psychiatry

Background:

• Bipolar disorder (BD) involves mood swings between mania/hypomania and depression.
• Previous studies linked rare copy number variations (CNVs) in synaptic genes to BD.
• A comprehensive analysis of CNVs in synaptic genes in BD was lacking.

Purpose of the Study:

• To investigate the association between rare CNVs overlapping with synaptic genes and bipolar disorder (BD) in the Japanese population.
• To identify specific synaptic genes and pathways implicated in BD pathogenesis.
• To expand the understanding beyond exonic CNVs to include other genomic regions.

Main Methods:

• Utilized array comparative genome hybridization (aCGH) to detect CNVs in 1839 BD patients and 2760 controls.
• Employed the Synaptic Gene Ontology database to identify CNVs overlapping with synaptic genes.
• Conducted gene-based analysis to compare CNV frequencies between BD and control groups, setting significance at a false discovery rate of 10%.

Main Results:

• Identified a significant association between CNVs in the RNF216 gene and BD (OR=4.51, FDR<10%).
• The BD-associated CNV in RNF216 partially overlapped with the 7p22.1 microduplication syndrome region.
• The postsynaptic membrane gene set was significantly associated with BD, with a nominally significant CNV in the GRM5 gene (P<0.05).

Conclusions:

• CNVs in RNF216 and genes related to the postsynaptic membrane contribute to bipolar disorder risk.
• These findings advance the understanding of the genetic underpinnings and pathogenesis of bipolar disorder.
• The study highlights the importance of considering non-exonic CNVs in synaptic genes for BD.