Approved Research

Causes and consequences of human trait variation

Lay summary

Humans vary tremendously across a wide range of traits, for example in colour, height, weight, blood pressure, and behaviour. Some of that variation is due to genetic effects or captured by known environmental factors. However, we still know very little about how genetic variation between people combined with their environmental exposures lead to differences in outcomes in life, including risk of common diseases such as cardiovascular disease, cancer and disorders of the brain, psychological and economic well-being and longevity. We aim to use genomic, trait and disease data in the UK Biobank to develop and apply statistical approaches to address questions about how genomic variation causes individual differences. The rationale for this approach is what we know that the DNA is essentially unchanged during a person's life and comes before a person is exposed to the environment.

We will use associations between DNA variants and knowledge about the genome to identify variants and genes that cause individual differences; develop and apply statistical approaches to use all genomic and trait data simultaneously to quantify the relationships between traits and test the limits of predicting an individual's risk of disease in the future; develop new phenotypes from existing genomic and trait data, quantify their genetic basis and how they are correlated with disease and other traits. These aims will take at least 3 and probably 6 years to address.

Understanding the genetic basis of relationships between molecular, physiological and behavioural phenotypes and life outcomes is of considerable research and public health interest. It will lead to a better understanding of the genetic factors and biochemical pathways underlying individual differences, including those for common diseases. The impact of this research will be new knowledge about factors that causes disease and adverse effects in life. Such knowledge may lead to new prevention or treatment strategies. Another impact will be the distribution of computer programs that other researchers can use in different datasets.