TY  - JOUR
AB  - 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.
AU  - De Santana Villasboas Arruda, A.L.
AU  - Khandaker, G.M.*
AU  - Morris, A.P.*
AU  - Smith, G.D.*
AU  - Huckins, L.M.*
AU  - Zeggini, E.
C1  - 70048
C2  - 55382
CY  - Heidelberger Platz 3, Berlin, 14197, Germany
TI  - Genomic insights into the comorbidity between type 2 diabetes and schizophrenia.
JO  - Schizophr.
VL  - 10
IS  - 1
PB  - Nature Portfolio
PY  - 2024
SN  - 2754-6993
ER  -