Lipoedema UK’s role in the Genetic Analysis of Lipoedema Project – St George’s University Hospitals NHS Foundation Trust
Professor Peter Mortimer
The Lymphoedema department at St George’s Hospital lead by Professor Peter Mortimer and Dr Kristiana Gordon has renowned expertise in diagnosing both Lymphoedema and Lipoedema. The department also takes part in extensive patient studies and genetic research in both of these areas, attempting to identify the defects in the genetic code that define both conditions.
Dr Kristiana Gordon
Having heard about the amazing work that the team was doing to advance the understanding of Lipoedema, Lipoedema UK wanted to get involved. Therefore, Dr Gordon, Dr Ostergaard and Professor Mortimer were invited to the Lipoedema UK’s 2016 conference explaining the research project. This lead to a large donation to continue their work.
Glen Brice and Dr Pia Ostergaard – Researchers from St George’s Hospital, London at Lipoedema UK Conference 2017
In 2017 Dr Pia Ostergaard and St George’s Nurse Glen Brice attended and gave an update at our Sheffield conference, over 50 of our conference members were able to enrol in the research project over the conference weekend. Patients were also recruited by the Lymphoedema Department of University Hospitals of Derby and Burton NHS Foundation Trust led by Professor Vaughan Keeley who work closely with St Georges on genetic studies of both lymphoedema and lipoedema.
Lipoedema UK were also able to arrange for other groups of patients to meet with Glen Brice, where tissue samples and statistics were taken over a two-hour period, which normally would have taken St George’s several weeks to arrange.
Thanks to these efforts, approximately 300 individuals have been consented to the study, 247 of these are lipoedema cases, the remainder unaffected relatives. Recruitment for the project has now closed, but the team at St George’s is currently analysing the many SF36 Quality of Life questionnaires that all the recruits so kindly have filled in and the group is hoping to publish their findings later this year.
The St George’s team also proposed to get Lipoedema included in Genomics England’s 100,000 Genomes Project https://www.genomicsengland.co.uk/). This is a NHS and National Institute for Health Research effort to provide a resource of 100,000 whole genomes from NHS patients with rare diseases and their families. The aim is to promote new genetic discovery and medical insights to those rare disease for which we still do not understand the genetic cause. Just over 90 individuals with lipoedema were recruited to the 100,000 Genomes Project and the St George’s team will have access to the Whole Genome Sequencing (WGS) data for those.
Dr Pia Ostergaard presenting at a Lipoedema conference, explaining the research project
The St George’s team has analysed the genetics of several lipoedema families, which is the traditional approach in a genetics study. The team thought they had some potential candidate genes, however, on further analysis these variants turns out to not have any pathogenic effect on protein function, i.e. these variants are deemed benign. Therefore, the hunt must continue.
The team therefore obtained genotyping data from over 170 of the recruited individuals, for use in a what is called a genomewide association study (GWAS). This is another type of genetic investigation, which researchers can use to decipher genetic diseases. The GWAS would allow the St George’s team to identify regions in the lipoedema cohort which are similar, but different to a control population. Thereby, regions with faults in the genetic code causing lipoedema can be highlighted. Still, this would not reveal the exact nature of the problem but would be an initial signpost. The team will then take the results from the GWAS and look in the WGS sequencing data from the 100,000 Genomes Project plus an additional 80+ Whole Exome Sequencing (WES) data available to the team. This would hopefully allow them to decipher the specific genetic defects causing this condition.
The St Georges’s team’s quest to understand lipoedema is continuing and will depend on renewed funding for the project.
Genomics England’s 100,000 Genomes Project (Update October 2019)
If you are a participant in the genetic researching project you may receive a standard letter from the genetic counsellor from St.George’s in reference to 100.000 Genome Project Update which states they have completed the whole genome sequencing but “no clear cause of the condition in the family has been identified.
The initial screen by the “Clinical Embassy” looks for any genes that were put on a candidate gene list and as, in the case of Lipoedema, there were not any good candidate genes (as none has been discovered), this gene list is really just excluding any primary lymphoedema and lipohyperdystrophies with known cause. The action at this point is that if no genes are identified, a clinical report will be generated.
What happens next, is that the data from the 100K project then moves into the “Research Embassy” at St Georges, who will then have access to the data and can start the proper work on trying to elucidate a genetic background. This step is going to take time and the research is only really just starting when it comes to analysing 100K data. St George’s bioinformatician will upload the files in the research environment. As this is whole genome sequencing, there are massive data files that need uploading (several Tb of data), so the computing is not a quick process but frustratingly will be slow as no one knows what they are looking for yet.
Lipedema Foundation Registry
The Lipedema Foundation based in the USA now have an online registry (Lipedema Foundation Registry LFR) established to help our lipedema community, including affected individuals, families, clinicians, and researchers. Lipoedema UK encourage all our members, their families and friends to take part. It’s goals are to:
learn more about lipedema
understand barriers to diagnosis
better manage symptoms
assess quality of life impact
develop new treatment approaches
This registry is only for:
– People with lipedema
– People who think they might have lipedema, and
– People who do not have lipedema (to use as comparison groups)
Participants under 18 must have an adult enroll in the registry on their behalf. The adult must:
– Be 18 years of age or older
– Be the parent, legal guardian, or other legally authorized representative of the participant
– Be willing and able to provide consent for the child under 18
– Obtain assent (agreement) from the minor participant, if they are between 13-17 years of age and are able to assent. Children under 13 are able to participate, although assent is not required.
Once a child turns 18, the Lipedema Foundation will contact the family and request that the participant provide his/her own consent to stay in the LFR.
Individuals from any country are welcome to participate in the LFR. Currently, the LFR is only available in English and participants must be able to read the consent and answer the surveys in English.
The Lipedema Foundation (LF) has developed an “Initial Survey” that should take approximately 60 minutes to complete. It will help provide direction for what types of research we should fund next.
To complete the survey please click on the image below. If you have any questions, comments or issues with the Registry – please contact Registry@lipedema.org.
Understanding the Causes of Lipoedema
Interview with Professor Peter Mortimer
Professor of Dermatological Medicine
Molecular and Clinical Sciences Institute (Dermatology Unit)
St. George’s, University of LondonLondon, England