Identification of genetic instruments of putative risk factors for Mendelian Randomization analyses of carcinogenic endpoints.

Epidemiological studies have identified risk factors for cancer, but establishing causal links have proven challenging. In order to circumvent this, we will use the state-of-the-art Mendelian randomization analysis to evaluate whether putative risk factors play causal roles in cancer disease.
We propose specifically i) to use baseline data along with genome-wide data from UK Biobank to identify gene variants (genetic instruments) associated with putative risk factors, ii) to validate genetic instruments using UKBB data, and finally iii) to evaluate the identified instruments in relation to specific cancers within UKBB and other association studies.
This proposal is consistent with UK Biobank’s mission of health-related research in the public interest. Our project will help to develop a wide range of genetic instruments that can be used to test causality of potential risk factors in observational epidemiologic studies of carcinogenic endpoints. The results can ultimately be translated into better prevention policies by informing on those risk factors that cause specific diseases. The proposed analysis will be performed using baseline data collected from UK Biobank participants, together with genome-wide genotyping data that is currently being generated on all study participants. We will initially use these data to agnostically identify specific gene variants (genetic instruments) that are associated with exposures of interest (e.g. obesity, hypertension etc.). The association between defined genetic instruments and specific diseases will subsequently be evaluated in other study populations that we have access to, examples including large genetic association studies of common cancers, such as lung cancer, prostate cancer, and breast cancer. Full cohort