Approved research

The Genetics of anthropometric traits ? Height, weight, BMI and waist circumference

Lay summary

Our question is `what are the genetic factors that lead to altered height, weight, BMI, waist-circumference and adiposity in today?s environment?? We will identify the genetic factors that: i) influence height ? a measure of growth in childhood. ii) influence weight, BMI, waist-circumference and adiposity. Excess adiposity predisposes individuals to common diseases including diabetes and heart disease. There is a genetic component to where people lie on the BMI scale. We will use UK Biobank to identify more of the genetic factors. iii) influence blood pressure, heart disease and diabetes through genetic effects on growth, BMI or adiposity. Our proposed research will address a fundamental health question - why are some individuals more overweight than others in today's obesogenic environment whilst others do not? There is very strong evidence that genetic factors account for some of these differences between individuals and yet we have not identified a large component of the genetic heritability of BMI, adiposity and obesity. We also argue that studying height provides an exemplar trait to assess the ability of genetic technologies and methods to identify the genetic components to common human traits. Our proposal will proceed in two phases. In phase 1 we will analyse all the genetic variants measured in the initial 150,000 individuals. We will analyse the approximately 800,000 genetic variants against BMI, height, weight, adiposity measures in all 150,000 individuals and against intermediate traits that may influence these outcomes, including diet, activity and exercise. We will use genetic variants associated with adiposity and metabolic traits to assess their role in metabolic disease outcomes such as type 2 diabetes, heart disease and hypertension. In phase2 we will repeat these analyses but using the dataset of 500,000. In phase 1 the 150,000 currently with genotype data and in phase 2 the full 500,000.

Scope extension:

Our question is "what are the genetic factors that lead to altered height, weight, BMI, waist circumeference and adiposity in today's environment ?

We will identify the genetic factors that:

1. i) influence height ? a measure of growth in childhood
2. ii) influence weight, BMI, waist-circumference and adiposity. Excess adiposity predisposes individuals to common diseases including diabetes and heart disease. There is a genetic component to where people lie on the BMI scale. We will use UK biobank to identify more of the genetic factors.

iii) influence blood pressure, heart disease and diabetes through genetic effects on growth, BMI or adiposity.

To do this we will use the main dataset and the optional questionnaire data (e.g. activity monitoring, food frequency etc.). The optional questionnaires were only completed by a subset of the UK Biobank and within these the prevalences of obesity will vary. This could therefore introduce bias into our analyses. We therefore will perform analyses to quantify this bias and account for it in our subsequent analyses.

NEW SCOPE

we would like to request access to the Proteomic data from the Pharma Proteomic Partnership: as outlined in the recent paper: https://www.biorxiv.org/content/10.1101/2022.06.17.496443v1 . Many of these proteins are correlated with growth and adiposity and we wish to assess their causal role using Mendelian randomisation and potentially identify new genetic associations using the full range of genetic data.