Neuroticism, well-being PGS predict mood, psychotic disorder onset

Polygenic scores (PGS) for neuroticism and subjective well-being are significantly associated with the risk of major mood and psychotic disorders, regardless of family history, but the predictive power of PGS for psychiatric illness is limited when family history is known, reports a study.

A team of investigators combined eight cohorts, with a total of 1,884 participants 2‒36 years of age, including 1,339 offspring of parents with mood or psychotic disorders who were prospectively assessed with diagnostic interviews over an average of 5.1 years.

The investigators also constructed PGS for depression, bipolar disorder, anxiety, attention deficit hyperactivity disorder (ADHD), schizophrenia, neuroticism, subjective well-being, p factor, and height (as a negative control). Finally, they used Cox regression to explore the associations between PGS, family history of major mental illness, and onsets of major mood and psychotic disorders.

A total of 435 onsets of major mood and psychotic disorders were recorded during follow-up. PGS for neuroticism (hazard ratio [HR], 1.23, 95 percent confidence interval [CI], 1.12‒1.36), schizophrenia (HR, 1.15, 95 percent CI, 1.04‒1.26), depression (HR, 1.11, 95 percent CI, 1.01‒1.22), ADHD (HR, 1.10, 95 percent CI, 1.00‒1.21), subjective well-being (HR, 0.90, 95 percent CI, 0.82‒0.99), and p factor (HR, 1.14, 95 percent CI, 1.04‒1.26) correlated with onsets.

Notably, the significant associations of PGS for neuroticism (HR, 1.19, 95 percent CI, 1.08‒1.31) and for subjective well-being (HR, 0.89, 95 percent CI, 0.81‒0.98) with onsets persisted after controlling for family history.

“Neuroticism and subjective well-being PGSs may complement family history in the early identification of persons at elevated risk,” the investigators said.