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Working Groups - Genetic modifiers -

The Genetic Modifiers Working Group aims to investigate genetic factors that influence the onset and progress of HD. Part of the difference in age of onset is determined by the CAG repeat length in the HD gene, but there are also other determinants that are not related to the CAG repeat. Any genes that influence the age of onset are likely to be important targets for therapy, as drugs that could modify their operation may also be able to alter the age of onset of the disease. Furthermore, specific symptoms of HD may be determined by genes other than the HD gene. Hence, knowing about these influences could also improve symptomatic treatments for HD patients.


The Genetic Modifiers Working Group aims to facilitate genetic studies on HD by all members of the working group and the wider network, and to set up studies to facilitate the availability of this information EHDN-wide.

Current projects

At the moment we are carrying out three major projects which aim to provide data for genetic analysis:
  1. Whole genome scan: CHDI will provide whole genome scan data from all participants of REGISTRY who have donated DNA samples. This means that most of the variation in the genome can be detected, enabling studies on whether specific changes in DNA are associated with the onset or progression of different aspects of HD.
  2. Improving the data available for genetic analysis: In order to collect onset data for a range of symptoms in REGISTRY, we have developed a questionnaire in parallel with a similar study in the USA called COHORT. The collection of data about the onset of behavioural changes as well as movement symptoms may help elucidate the underlying genetics of HD. We have also improved the way family history data is collected within REGISTRY and are now aiming to distribute some funds to help HD study sites collect and validate these family history data. These are essential for working out whether the symptoms that we wish to investigate are determined genetically.
  3. To provide a forum for clinicians, scientists and geneticists to share ideas about collection and analysis of genetic and other data. The ultimate goal is to enable high quality scientific studies that illuminate the pathophysiology in the course of HD. This might, for instance, help decide which scientific findings in disease models are most relevant to HD in humans. In turn this would indicate which models are most useful for particular types of treatment trials.
Study participation

The genetic modifiers study is one of the core studies of REGISTRY. It requires donation of blood samples for DNA extraction. To illuminate the pathophysiology of HD, genetic data are analysed together with relevant clinical data obtained through REGISTRY. This includes the family history data and the clinical characteristics questionnaire asking about the age of onset of specific symptoms. These data are assessed only once and then updated from information given longitudinally in subsequent visits. All data are pseudonymised before analysis.

The Genetic Modifiers Working Group has approximately 30 active members (April 2008). With the advent of real data we very much hope to expand! We welcome geneticists and statistical geneticists with an interest in HD and analysis of complex genetics, as well as all EHDN members that have an interest in genetics and wish to propose specific studies when the genetic data become available.


Lead Facilitators

Lesley Jones
Executive Committee, Lead Facilitator Genetic Modifiers
School of Medicine, Cardiff University, Psychological Medicine and Neurology, Heath Park
Postal address: Henry Wellcome Building
CF14 4XN Cardiff
phone: +44 2920 687054
fax: +44 2920 687068
homepage: medicine.cf.ac.uk/en/person/dr-lesley-jo...

Associated Language Area Coordinator (Lanco)

, Portugal