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Exploring shared genetic bases and causal relationships of schizophrenia and bipolar disorder with 28 cardiovascular and metabolic traits

Published online by Cambridge University Press:  26 July 2018

Hon-Cheong So*
Affiliation:
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Kunming Institute of Zoology and The Chinese University of Hong Kong, Shatin, Hong Kong
Kwan-Long Chau
Affiliation:
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
Fu-Kiu Ao
Affiliation:
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
Cheuk-Hei Mo
Affiliation:
Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
Pak-Chung Sham
Affiliation:
Department of Psychiatry, University of Hong Kong, Pokfulam, Hong Kong Centre for Genomic Sciences, University of Hong Kong, Pokfulam, Hong Kong State Key Laboratory for Cognitive and Brain Sciences, University of Hong Kong, Pokfulam, Hong Kong Centre for Reproduction, Development and Growth, University of Hong Kong, Pokfulam, Hong Kong
*Corresponding
Author for correspondence: Hon-Cheong So, E-mail: hcso@cuhk.edu.hk

Abstract

Background

Cardiovascular diseases represent a major health issue in patients with schizophrenia (SCZ) and bipolar disorder (BD), but the exact nature of cardiometabolic (CM) abnormalities involved and the underlying mechanisms remain unclear. Psychiatric medications are known risk factors, but it is unclear whether there is a connection between the disorders (SCZ/BD) themselves and CM abnormalities.

Methods

Using polygenic risk scores and linkage disequilibrium score regression, we investigated the shared genetic bases of SCZ and BD with 28 CM traits. We performed Mendelian randomization (MR) to elucidate causal relationships between the two groups of disorders. The analysis was based on large-scale meta-analyses of genome-wide association studies. We also identified the potential shared genetic variants and inferred the pathways involved.

Results

We found tentative polygenic associations of SCZ with glucose metabolism abnormalities, adverse adipokine profiles, increased waist-to-hip ratio and visceral adiposity (false discovery rate or FDR<0.05). However, there was an inverse association with body mass index. For BD, we observed several polygenic associations with favorable CM profiles at FDR<0.05. MR analysis showed that SCZ may be causally linked to raised triglyceride and that lower fasting glucose may be linked to BD. We also identified numerous single nucleotide polymorphisms and pathways shared between SCZ/BD with CM traits, some of which are related to inflammation or the immune system.

Conclusions

Our findings suggest that SCZ patients may be genetically predisposed to several CM abnormalities independent of medication side effects. On the other hand, CM abnormalities in BD may be more likely to be secondary. However, the findings require further validation.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2018 

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