Investigating associations between genetic risk for bipolar disorder and cognitive functioning in childhood

Sumit Mistry*, Valentina Escott-Price, Arianna D. Florio, Daniel J. Smith, Stanley Zammit

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

1 Citation (Scopus)

Abstract

Introduction: Identifying phenotypic manifestations of genetic risk for bipolar disorder (BD) in childhood could increase our understanding of aetiological mechanisms. Aims: To examine whether BD genetic risk is associated with childhood (age 8 years) cognitive function. Methods: Using data from the Avon Longitudinal Study of Parents and Children, we examined associations between polygenic risk scores for BD (BD-PRS) derived using Psychiatric Genomics Consortium summary data at p-thresholds (PT) ≤0.01 (primary) and ≤0.5 (secondary) and several cognitive domains (sample sizes 5,613 to 5,936). We also examined whether associations were due to SNPs that have shared risk effects on schizophrenia (SZ). Results: At PT≤0.01, the BD-PRS was associated with poorer executive functioning (ß= -0.03, 95%CI -0.06, -0.01; p = 0.013), and, more weakly with poorer processing speed (ß = -0.02, 95%CI -0.05, 0.02; p = 0.075). Evidence of association with both poorer processing speed (p = 0.016) and performance IQ (p = 0.018) was stronger at PT≤0.5. Associations with performance IQ and processing speed were primarily driven by genetic effects that are shared with SZ risk, but there was some evidence of bipolar-specific genetic effects on childhood executive functioning. Limitations: The BD-PRS still explains only a small proportion of the variance for BD which will have reduced power to detect associations. Conclusions: Genetic risk for BD manifests as impaired cognition in childhood, and this is driven by risk SNPs that are also shared with SZ genetic risk. Further elucidation of which cognitive domains are most affected by genetic risk for BD could help understanding of aetiology and improve prediction of BD.

Original languageEnglish
Pages (from-to)112-120
Number of pages9
JournalJournal of Affective Disorders
Volume259
Early online date19 Aug 2019
DOIs
Publication statusPublished - 1 Dec 2019

Keywords

  • Cognition
  • Genetics
  • Bipolar disorder
  • ALSPAC
  • Polygenic risk score

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