Extensive bidirectional genetic overlap between bipolar disorder and cardiovascular disease phenotypes
| Autor: | Shahram Bahrami, Olav B. Smeland, Kevin S. O’Connell, Torbjørn Elvsåshagen, Oleksandr Frei, Anders M. Dale, Alexey A. Shadrin, Linn Rødevand, Guy Hindley, Trine Vik Lagerberg, Srdjan Djurovic, Yunhan Chu, Nils Eiel Steen, Ole A. Andreassen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Bipolar Disorder genetic structures Genome-wide association study Neurosciences. Biological psychiatry. Neuropsychiatry Disease macromolecular substances Biology Predictive markers Polymorphism Single Nucleotide Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Polymorphism (computer science) medicine Genetic predisposition Humans Genetic Predisposition to Disease cardiovascular diseases Bipolar disorder Biological Psychiatry Genetic association 2. Zero hunger Genetics medicine.disease Personalized medicine Comorbidity 3. Good health Psychiatry and Mental health Phenotype 030104 developmental biology Cardiovascular Diseases Genetic Loci Psychiatric disorders Body mass index 030217 neurology & neurosurgery Genome-Wide Association Study RC321-571 |
| Zdroj: | Translational Psychiatry Translational Psychiatry, Vol 11, Iss 1, Pp 1-9 (2021) |
| ISSN: | 2158-3188 |
| Popis: | Patients with bipolar disorder (BIP) have a high risk of cardiovascular disease (CVD), despite considerable individual variation. The mechanisms underlying comorbid CVD in BIP remain largely unknown. We investigated polygenic overlap between BIP and CVD phenotypes, including CVD risk factors and coronary artery disease (CAD). We analyzed large genome-wide association studies of BIP (n = 51,710) and CVD phenotypes (n = 159,208–795,640), using bivariate causal mixture model (MiXeR), which estimates the total amount of shared genetic variants, and conjunctional false discovery rate (FDR), which identifies specific overlapping loci. MiXeR revealed polygenic overlap between BIP and body mass index (BMI) (82%), diastolic and systolic blood pressure (20–22%) and CAD (11%) despite insignificant genetic correlations. Using conjunctional FDR n = 69), systolic (n = 53), and diastolic (n = 53) blood pressure, of which 22 are novel BIP loci. There was a pattern of mixed effect directions of the shared loci between BIP and CVD phenotypes. Functional analyses indicated that the shared loci are linked to brain-expressed genes and involved in neurodevelopment, lipid metabolism, chromatin assembly/disassembly and intracellular processes. Altogether, the study revealed extensive polygenic overlap between BIP and comorbid CVD, implicating shared molecular genetic mechanisms. The mixed effect directions of the shared loci suggest variation in genetic susceptibility to CVD across BIP subgroups, which may underlie the heterogeneity of CVD comorbidity in BIP patients. The findings suggest more focus on targeted lifestyle interventions and personalized pharmacological treatment to reduce CVD comorbidity in BIP. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|