During the last 15 years, human geneticists have made enormous progress toward understanding how genetics impacts human traits (such as height or bodyweight) and diseases (such as diabetes or depression). The UK Biobank has made a huge contribution to this, by providing a unique dataset of genetic data on nearly half a million British participants.
One key observation from this work is the finding that for most traits and diseases, there are thousands, or even tens of thousands of genetic variants across the human genome that influence one’s risk of getting that disease. In this way, most human traits are very different from the basic genetic models that we teach in schools. For example for Mendel’s peas, traits such as plant size were controlled by a single mutation in a single gene. A key component of our work is to understand why so many positions in the genome affect trait risk. We are also interested in related questions including: How does your genotype (i.e., all of the genetic variations in your genome) affect your risk of disease? How can we predict who is at risk of disease? How do non-genetic factors such as diet or exercise impact disease risk? And — bearing in mind that genetic variation in the current population is shaped by evolutionary processes that have taken place in the human species in the last million years — how have the processes of evolution including natural selection and random chance shaped the landscape of disease risk in the British population?
We request that this project be approved initially for a three-year term, to give us time to explore these complex questions in our lab.