: Return 2690

Notes

In this study, UK Biobank data from almost 130,000 people were studied to examine the relationship between the genetic risk factors for trauma exposure and depression, looking at those people who do and do not report exposure to traumatic events. The genetic risk for developing depression when people had reported being exposed to trauma was found to be double that for people who didn t report trauma exposure. Simulations showed that this was not confounded by the strong, positive genetic correlation between depression and reported trauma exposure. Furthermore, the findings also provided evidence that reported trauma exposure is partially heritable.

Note: GWAS analyses from this study contributed towards a further publication (Dalvie et al, 2020) which is also attached.

Application 16577

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
4006	16577	Genetic comorbidity between major depression and cardio-metabolic traits, stratified by age at onset of major depression	14 Oct 2021
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

1 Publication

Pub ID	Title	Author(s)	Year	Journal
2691	Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank	Jonathan R. I. Coleman (+25)	2020	Molecular Psychiatry

Application:	16577, Investigations of the genetic overlap between internalising psychiatric disorders and co-morbid physical health disorders.
Title:	Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank
Size:	679260 B
Archived:	30 Oct 2020
Stability:	Complete
Personal:	No individual-level data