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Genomic insights into the comorbidity between type 2 diabetes and schizophrenia.
Schizophr. 10:22 (2024)
Multimorbidity represents an increasingly important public health challenge with far-reaching implications for health management and policy. Mental health and metabolic diseases have a well-established epidemiological association. In this study, we investigate the genetic intersection between type 2 diabetes and schizophrenia. We use Mendelian randomization to examine potential causal relationships between the two conditions and related endophenotypes. We report no compelling evidence that type 2 diabetes genetic liability potentially causally influences schizophrenia risk and vice versa. Our findings show that increased body mass index (BMI) has a protective effect against schizophrenia, in contrast to the well-known risk-increasing effect of BMI on type 2 diabetes risk. We identify evidence of colocalization of association signals for these two conditions at 11 genomic loci, six of which have opposing directions of effect for type 2 diabetes and schizophrenia. To elucidate these colocalizing signals, we integrate multi-omics data from bulk and single-cell gene expression studies, along with functional information. We identify putative effector genes and find that they are enriched for homeostasis and lipid-related pathways. We also highlight drug repurposing opportunities including N-methyl-D-aspartate (NMDA) receptor antagonists. Our findings provide insights into shared biological mechanisms for type 2 diabetes and schizophrenia, highlighting common factors that influence the risk of the two conditions in opposite directions and shedding light on the complex nature of this comorbidity.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Nogo-b Receptor; R Package; Risk; Association; Expression; Digoxin; Brain; Mechanisms; Regression; Disorders
ISSN (print) / ISBN
2754-6993
e-ISSN
2754-6993
Journal
Schizophrenia
Quellenangaben
Volume: 10,
Issue: 1,
Article Number: 22
Publisher
Nature Publishing Group
Publishing Place
Heidelberger Platz 3, Berlin, 14197, Germany
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Translational Genomics (ITG)
Grants
NIEHS
NCI
NHGRI
NHLBI
NIDA
NIMH
NINDS - Medical Research Council (MRC)
University of Bristol
Wellcome Trust
UK Medical Research Council
UK National Institute of Health Research Bristol Biomedical Research Centre
National Institutes of Health: NIMH
Common Fund of the Office of the Director of the National Institutes of Health
NCI
NHGRI
NHLBI
NIDA
NIMH
NINDS - Medical Research Council (MRC)
University of Bristol
Wellcome Trust
UK Medical Research Council
UK National Institute of Health Research Bristol Biomedical Research Centre
National Institutes of Health: NIMH
Common Fund of the Office of the Director of the National Institutes of Health