Associations between mosaic loss and schizophrenia or bipolar disorder of young age

Area of Science:

• Genetics
• Psychiatry
• Cell Biology

Background:

• Mosaic chromosomal alterations (mCAs) are known to accumulate in brain tissue and are implicated in psychiatric disorders.
• The role of mCAs in circulating blood concerning schizophrenia (SCZ) and bipolar disorder (BD) requires further investigation.

Purpose of the Study:

• To evaluate the association between mCAs in blood and the prevalence of SCZ and BD.
• To explore the influence of cell fraction (CF) on mCAs and their potential interaction with genetic risk scores in SCZ and BD.

Main Methods:

• Detected mCAs in blood samples from a large cohort including SCZ, BD, and control subjects.
• Utilized age-adjusted logistic regression models to assess associations, including subgroup analyses for age and high cell fraction (CF) mCAs.
• Examined the interaction between mCAs and polygenic risk scores (PRS) for SCZ and BD.

Main Results:

• Autosomal mCAs, particularly loss events, were significantly increased in both SCZ and BD patients.
• These associations were more pronounced in younger individuals, with higher effect sizes for loss events correlating with increased CF.
• High cell fraction loss events demonstrated an interaction with the polygenic risk score in SCZ.

Conclusions:

• A high burden of mosaic losses in blood is characteristic of SCZ and BD, especially in young patients, indicating common somatic pathophysiological mechanisms.
• The findings suggest a potential interplay between genetic predisposition and environmental factors in the development of SCZ.