Project: Deciphering the Genetic Basis of Lipedema

Principal Investigator: Alan Pittman, PhD
Co-Principal Investigator: Pia Ostergaard, PhD
Co-Principal Investigator: Kristiana Gordon, PhD

St George's, University of London
Molecular and Clinical Sciences
London, UK

Summary

This research seeks to explore the role of genetics in Lipedema with the aim of identifying genetic factors that increase an individual’s likelihood of developing Lipedema. We will study the genomes of Lipedema families to identify genetic variants that are inherited in affected family members. We will also compare groups of unrelated Lipedema patients to healthy control groups to identify common genetic variants that serve as risk factors for Lipedema at the population level. 

By identifying new genes this work will lead to new avenues of research in therapeutics and diagnostics, ultimately improving the lives of people with Lipedema.

Background

There is a strong family history of Lipedema in approximately 50% of cases, suggesting that genetics is likely to play a significant role in susceptibility to Lipedema.

In our pilot study, we observed a pattern of inheritance suggestive of a single genetic variant driving Lipedema in many families. For the cases with no family history available we conducted a genome-wide association study where the genetics of the patients are analyzed collectively and compared to a group of healthy individuals. We identified potential variants, common in the population, associated with an increased risk of developing Lipedema. Thus, our research suggests a complex genetic architecture, involving rare variants within families, and common genetic variants at the population level that serve as risk factors for Lipedema.

Currently, there is a considerable gap in the understanding of the genetic basis of Lipedema and we are pursuing both strategies to identify genetic causes of Lipedema..

Methodology

This is a genetic study to identify high-risk variants in genes within Lipedema families, and to identify common genetic risk factors for Lipedema in the population.

We will be comparing the genomes (or the exome; the part of the genome that codes for genes) of Lipedema patients within families to look for genetic variants that segregate between affected and unaffected family members. We will aim to characterize how these Lipedema-associated variants may be affecting the normal function of the gene they reside in. We will also use a statistical approach to identify genes that harbor a significant “burden” of rare genetic variants in all the Lipedema patients combined compared to matched control samples.

In addition, we will be expanding our search for common genetic susceptibility variants by including additional patient cohorts we are collecting from Spain and Australia, to not only strengthen the findings of our previous GWAS but to also identify novel genetic associations with Lipedema. In this, we will be comparing the frequency of common genetic variants across the entire genome in Lipedema patients compared to matches control samples.

Expected outcomes

We hypothesize there are high-penetrance rare variants segregating from parents to children in families and there will be a burden of rare variants in particular genes in Lipedema patients. We also hypothesize that common variants identified through the pilot-study can be validated in further patient cohorts, and that additional signals will be identified.

This work will provide the community with new insights into the genetic architecture of Lipedema, hopefully identifying a set of novel, highly-penetrant genes that run in families causing Lipedema, and also common genetic risk variants, present in the general population, that predispose to Lipedema.

Practical implementations of results

This work will improve our understanding of the genetic background of Lipedema by identifying additional genes or gene sets involved in disease development.

By identifying new genetic targets and understanding risk factors, this work will have direct application in genetic diagnostics. This work could also open new avenues for biological research. For example, the most promising genes could be developed into in vivo models to enable the elucidation of disease manifestation and progression. This could eventually lead to the identification of drug targets and the development of therapies for Lipedema. 

Our Research Grantees by:   Topic | Recent Projects | Past Projects

LF36_21