ABSTRACT
BACKGROUND: Individuals with psychiatric disorders have elevated rates of type 2 diabetes comorbidity. Although little is known about the shared genetics and causality of this association. Thus, we aimed to investigate shared genetics and causal link between different type 2 diabetes and psychiatric disorders. METHODS: We conducted a large-scale genome-wide cross-trait association study(GWAS) to investigate genetic overlap between type 2 diabetes and anorexia nervosa, attention deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, schizophrenia, anxiety disorders and Tourette syndrome. By post-GWAS functional analysis, we identify variants genes expression in various tissues. Enrichment pathways, potential protein interaction and mendelian randomization also provided to research the relationship between type 2 diabetes and psychiatric disorders. RESULTS: We discovered that type 2 diabetes and psychiatric disorders had a significant correlation. We identified 138 related loci, 32 were novel loci. Post-GWAS analysis revealed that 86 differentially expressed genes were located in different brain regions and peripheral blood in type 2 diabetes and related psychiatric disorders. MAPK signaling pathway plays an important role in neural development and insulin signaling. In addition, there is a causal relationship between T2D and mental disorders. In PPI analysis, the central genes of the DEG PPI network were FTO and TCF7L2. CONCLUSION: This large-scale genome-wide cross-trait analysis identified shared genetics andpotential causal links between type 2 diabetes and related psychiatric disorders, suggesting potential new biological functions in common among them.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Autism Spectrum Disorder , Bipolar Disorder , Depressive Disorder, Major , Diabetes Mellitus, Type 2 , Humans , Depressive Disorder, Major/genetics , Autism Spectrum Disorder/genetics , Bipolar Disorder/genetics , Attention Deficit Disorder with Hyperactivity/genetics , Genome-Wide Association Study , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/geneticsABSTRACT
ABSTRACT: Obsessive-compulsive disorder (OCD) has a bidirectional relationship with metabolic disorders. The purposes of this review are to decipher the links between OCD and metabolic disorders and to explore the etiological mechanism of OCD in metabolism, which may aid in early identification of and tailored interventions for OCD and metabolic disorders.
Subject(s)
Metabolic Diseases , Obsessive-Compulsive Disorder , Humans , Obsessive-Compulsive Disorder/therapyABSTRACT
AIMS: Epidemiological studies demonstrate an association between classes of obesity and psychiatric disorders, although little is known about shared genetics and causality of association. Thus, we aimed to investigate shared genetics and causal link between different classes of obesity and psychiatric disorders. METHODS: We used genome-wide association study (GWAS) summary data range from 9725 to 500,199 sample sizes of European descent, conducted a large-scale genome-wide cross-trait association study to investigate genetic overlap between the classes of obesity and anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, schizophrenia, anxiety disorders and Tourette syndrome. We conducted transcriptome-wide association study analysis (TWAS) to identified variants regulated gene expression in those related disorders. Finally, pathway enrichment analysis to identified major pathways. RESULTS: In the combined analysis, we replicated 211 previously reported loci and discovered 58 novel independent loci that were associated with all three classes of obesity and related psychiatric disorders. Functional analysis revealed that the identified variants regulated gene expression in major tissues belonging to exocrine/endocrine, digestive, circulatory, adipose, digestive, respiratory, and nervous systems, such as DCC, NEGR1, INO80E. Mendelian randomization analyses suggested that there may be a two-way or one-way causal relationship between obesity and psychiatric disorders. CONCLUSION: This large-scale genome-wide cross-trait analysis identified shared genetics and potential causal links between classes of obesity and psychiatric disorders (attention deficit hyperactivity disorder, autism spectrum disorder, anorexia nervosa, major depressive disorder, schizophrenia, and obsessive-compulsive disorder). Such shared genetics suggests potential new biological functions in common among them.
