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

Mistry, S., Escott-Price, V., Florio, A. D., Smith, D. J. and Zammit, S. (2019) Investigating associations between genetic risk for bipolar disorder and cognitive functioning in childhood. Journal of Affective Disorders, 259, pp. 112-120. (doi: 10.1016/j.jad.2019.08.040)

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.

• Item Type: Articles
• Additional Information: SM is funded by Mental Health Research UK and DJS is a Lister Institute Prize Fellow (2016–2021). The UK Medical Research Council and the Wellcome Trust (102215/2/13/2), and the University of Bristol provide core support for ALSPAC.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Smith, Professor Daniel
• Authors: Mistry, S., Escott-Price, V., Florio, A. D., Smith, D. J., and Zammit, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
• Journal Name: Journal of Affective Disorders
• Publisher: Elsevier
• ISSN: 0165-0327
• ISSN (Online): 1573-2517
• Published Online: 19 August 2019
• Copyright Holders: Crown Copyright © 2019 Published by Elsevier B.V.
• First Published: First published in Journal of Affective Disorders 259:112-120
• Publisher Policy: Reproduced in accordance with the publisher copyright policy