Investigation of phenotypes associated with genetic variants of metabolic interest (IPGMI)

Study code

Lead researcher
Professor Sir Stephen O'Rahilly

Study type
Samples and data

Institution or company
University of Cambridge

Researcher type

Speciality area
Genomics and Rare Diseases, Metabolic and Endocrine Disorders

Recruitment Site


We wish to identify individuals within the Cambridge Bioresource that carry potentially functional variants in nuclear receptors that are understood to regulate human metabolism. The primary aim of this study is to identify cases and does not require the recall of participants in the first instance.  

In order to identify cases we will undertake specific exon sequencing of the selected genes (PPARA, LXR, ERR) on anonymised participant DNA samples from the entire Cambridge Bioresource. This will be undertaken by the Metabolic Research Laboratory core genomic facility using a pooled sequencing approach. The DNA samples will be pooled robotically into pools of 20 participant samples. In the event that a variant of interest is identified within a pool we will undertake Sanger sequencing of the particular gene of interest in each participant of that pool, this will allow us to identify which DNA sample of the 20 harbours the variant.  All DNA samples will be stored at the Metabolic Research Laboratory where access is restricted to authorised personnel and handled in accordance with specific material transfer agreements. 

Missense variants identified within this cohort will be stratified based on predictive modelling supplemented by mapping mutations onto the known structures of the proteins. In vitro assessment of protein function will be undertaken to validate these predictions. Once we have identified and stratified these variants by functionality we will make application to undertake human phenotypic studies that will be tailored specifically to the gene being evaluated.   

Organisation: This study is organised by Professor Stephen O’Rahilly based at the Metabolic Research Laboratories, the University of Cambridge.