Approved Research

Understanding the role of rare and common genetic variation in the causes and consequences of obesity and related conditions

Lay summary

For the first time in human history a large proportion of people will be living into advanced old age having spent their whole adult lives overweight. This change is likely to have major implications for lots of diseases, not just diabetes and heart disease, but we do not fully understand the causes and consequences of carrying excess weight for many decades. For some people, it may not cause many problems, for others with a similar weight history it may cause multiple long term conditions.

Aims: To use genetics to improve our understanding of the causes and consequences of excess weight.

Scientific rationale: We will focus our research on identifying the role of rare genetic variation in the causes and consequences of excess weight. We have been able to study the human genome and its influence on common disease for 16 years, but these studies have been largely limited to common variation - the DNA sequence differences present in 1 in 2 to 1 in 50 people. New technologies now mean we can study a much larger set of genetic variation - that which occurs in 1 in 50 to 1 in 5000 people. Although this type of variation occurs in smaller numbers of people, it could still involve 100,000s of people in the one country and result in much larger risks of disease.

Project duration: This project will continue to provide scientific understanding for a further 10-20 years, given that UK Biobank participants will age through their 70s, 80s and 90s and develop multiple long term conditions, many of them associated with excess weight.

Public health impact:  Our research will help better understand the causes of excess weight and the reasons why two people of similar age, sex and BMI can have very different risks of disease. This work may help personalise or stratify treatments and preventions in a more cost effective way. The research will also raise awareness of the role of obesity related interventions that target the environment as well as individuals or groups.