It is imperative to understand the specific and shared etiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression. Polygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic etiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in 11 data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank. All cardio-metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease, and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression. The phenotypic associations between major depression and cardio-metabolic traits may partly reflect their overlapping genetic etiology irrespective of the age depression first presents.
Investigations of the genetic overlap between internalising psychiatric disorders and co-morbid physical health disorders.
Identify changes in DNA that increase the risk for psychiatric disorders alone (specifically the internalising disorders: depression, anxiety including OCD, and related disorders), and for these disorders in the presence of co-morbid physical disorders (autoimmune disorders, including rheumatoid arthritis, and non-immune disorders, including type 2 diabetes, migraine, chronic pain, obesity and body-mass index). Disorder status will be determined from the UK Biobank adjudicated health outcomes, including data from primary care , hospitals, and self-report. We will also explore whether the variants associated with each psychiatric disorder predict the likelihood that an individual has a given physical disorder. Understanding how genetics influence psychiatric disorders, and the relationship between psychiatric and physical disorders, will provide much-needed insight into the underlying biology. As well as increasing our understanding of interactions between the brain and body, this may identify target systems for the development of novel treatments in psychiatry; for example, the re-purposing of anti-inflammatory drugs for the treatment of schizophrenia and depression is a promising area of ongoing research. Furthermore, identification of shared genetic risk factors could assist in diagnosis by determining whether a given patient is high or low risk. Genotype information is being produced on the UK Biobank sample. We will use this to perform genome-wide association studies using publicly-available software packages, testing thousands of DNA variants for their association with different disorders. We will compare individuals with internalising disorders to controls, as well as comparing those with both a psychiatric and a physical disorder to those with only one (to identify genetic variants associated with having both disorders).
We will also explore the genetic overlap between a given psychiatric disorder and associated physical disorders, using the results from the association studies and publicly-available software packages. Full cohort
|Lead investigator:||Dr Gerome Breen|
|Lead institution:||King's College London|
4 related Returns
|Return ID||App ID||Description||Archive Date|
|2643||16577||GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores||29 Oct 2020|
|2690||16577||Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank||30 Oct 2020|
|2708||16577||Indicators of mental disorders in UK Biobank - A comparison of approaches||30 Oct 2020|
|2663||16577||Mental health in UK Biobank - development, implementation and results from an online questionnaire completed by 157,366 participants: a reanalysis||29 Oct 2020|