Rare copy number variation in posttraumatic stress disorder

Area of Science:

• Genetics
• Psychiatry
• Neuroscience

Background:

• Posttraumatic stress disorder (PTSD) is a heritable psychiatric condition.
• Copy number variation (CNV) is a type of genetic variation implicated in psychiatric disorders.
• Previous large-scale investigations of CNV in PTSD were lacking.

Purpose of the Study:

• To investigate the association between CNV burden and PTSD symptoms.
• To identify specific CNV regions or genes associated with PTSD risk.
• To explore the role of neurodevelopmental CNV regions in PTSD etiology.

Main Methods:

• A large-scale association study involving 114,383 participants (13,036 cases, 101,347 controls) of European ancestry.
• CNVs were identified using two calling algorithms and meta-analyzed across cohorts.
• Analysis included genome-wide CNV burden, gene-set enrichment, and CNVs overlapping neurodevelopmental regions.

Main Results:

• A significant association was found between the total span of deletions in neurodevelopmental CNV regions and PTSD (P = 6.3 × 10^-8).
• This genome-wide neurodevelopmental CNV burden explained 0.034% of PTSD symptom variation.
• The 15q11.2 BP1-BP2 microdeletion region showed a significant association with PTSD (P = 0.0002).
• While 22 nervous system gene pathways were significant, these were not robust after excluding neurodevelopmental regions.

Conclusions:

• CNV burden, particularly within neurodevelopmental regions, is significantly associated with PTSD.
• The 15q11.2 microdeletion is a specific CNV region linked to PTSD.
• Further research with larger sample sizes and improved CNV detection methods is warranted to fully elucidate the role of CNVs in PTSD.