New insights into the endophenotypic status of cognition in bipolar disorder: Genetic modelling study of twins and siblings

Background Twin studies have lacked statistical power to apply advanced genetic modelling techniques to the search for cognitive endophenotypes for bipolar disorder. Aims To quantify the shared genetic variability between bipolar disorder and cognitive measures. Method Structural equation modelling was performed on cognitive data collected from 331 twins/siblings of varying genetic relatedness, disease status and concordance for bipolar disorder. Results Using a parsimonious AE model, verbal episodic and spatial working memory showed statistically significant genetic correlations with bipolar disorder (r_g = |0.23|-|0.27|), which lost statistical significance after covarying for affective symptoms. Using an ACE model, IQ and visual-spatial learning showed statistically significant genetic correlations with bipolar disorder (r_g = |0.51|-|1.00|), which remained significant after covarying for affective symptoms. Conclusions Verbal episodic and spatial working memory capture a modest fraction of the bipolar diathesis. IQ and visual-spatial learning may tap into genetic substrates of non-affective symptomatology in bipolar disorder.