Principal Investigator: Dr Lavinia Paternoster
Department: MRC Integrative Epidemiology Unit
Institution: University of BristolTags: 10074, Atopy, Autoimmune disease, causality, Eczema, genetics
Collaborating Institutions and Addresses
QIMR Berghofer Medical Research Institute, Genetics and Computational Biology, 300 Herston Road, Herston, Queensland 4006, Australia
NOTE – MRC funded – grant number MR/J012165/1
1a: Eczema is a heritable chronic relapsing skin condition, common in early childhood, which can persist into adulthood. Eczema sufferers are at increased risk of other atopic conditions and other health problems.
Several genes have been identified which influence predisposition to eczema. Some of these genes are also important in other diseases, such as asthma, hay fever, inflammatory bowel disease and psoriasis.
We propose to use UK Biobank to investigate the genetic overlap between eczema and other related diseases and where possible, explore the causal relationships.
1b: As a resource that has collected a breadth of disease data on a very large number of individuals and with genome-wide genotype data available, UK Biobank provides a unique opportunity to study the genetic overlap between eczema and other diseases.
Through identification of genetic variants and causal relationships we aim to improve the understanding of the mechanisms of pathophysiology of these serious diseases. This provides opportunities to improve diagnosis and identify novel targets for treatment, in line with UK Biobank’s core principles.
1c: Phenotypic data collected by UKBiobank will be used to class individuals as ‘cases’ or ‘controls’ for the diseases of interest.
Genome-wide genetic data will be used to identify genetic variants that differ or are consistent between individuals with different disease profiles.
We will use a technique called mendelian randomisation (where a genetic instrument for the exposure of interest is used) to determine if there are causal relationships between atopic disease and other conditions, such as obesity, depression and lung cancer.
1d: We propose to use the full cohort of 500,000 people. For each of the conditions under study we require large numbers of cases and controls to have sufficient power to detect genetic differences.
- Investigate genetic overlap between immune traits, such as eczema, and other disorders. The research group has advised UK Biobank that they will approach this in a relatively hypothesis-free way by exploring how the genetics of immune-related disorders are manifest in phenotypically in the general population.
- “The genes associated with eczema are important in other immune diseases and of particular interest are the autoimmune disorders such as inflammatory bowel disease and psoriasis. It is then interesting to study the overlap between genetic risk factors for eczema and other immune conditions as well as how being a carrier of these genes manifests itself in the general population before the manifestations of symptoms of the disease, potentially as other disorders such as depression. Therefore the additional variables requested cover a range from anthropometric and general health (muscloskeletal and cardiovascular measures) to the blood counts as well as depression and cognitive measures. As mentioned in the application, increased understanding of the genetic overlap between different conditions increases our understanding of the aetiology and underlying mechanisms of these diseases as well as providing useful information of drug repositioning/off-target effects on other conditions.”