Information for participants

Thank you to everyone taking part in the 100,000 Genomes Project.

We are very grateful for your participation. It is helping to increase understanding of the genetic causes of rare diseases and cancer.

Please do let us know suggestions for further FAQs that you think would be helpful for us to answer. Please contact us at [email protected].

Frequently Asked Questions: General

Please inform your GP before you move house so that your records can be easily tracked and your results returned as quickly as possible.

Genomics England will always return results to the healthcare professional who asked you to join the Project. If you have moved since joining, that healthcare professional may either arrange to pass the results on to your new specialist, or arrange for you to go back see them again for the results.

Neither Genomics England nor the hospital where you took part will be able tell you exactly when your results will be back. This is because we have to focus on the work we are doing to return everyone’s results as quickly as possible. We have started returning results, but these need to be checked by NHS labs before they go back to patients. Over time this will become quicker, but things often take longer at the start of a big project like this because everything has to be set up and tested. Results will be returned to people throughout 2017 and 2018.

The Project is sequencing the whole genome of every participant – this lays it all down on file for future reference. So far our analysis of this data has been focusing on your genes – the 23,000 bits of that genome that play an active role in making your body do what it does. We use very sophisticated ‘gene panels’ to compare your genes against the ones that we know are associated with certain medical conditions. Beyond the genes, we have also begun to analyse other variants – this expands how much of your genome that we look at. In the very near future, we will also be able to use new technology to look at more bits between your genes, which will help us to find more answers for you.

When you join this Project, your blood sample is sent to Genomics England alongside information about your clinical features, coded in something called HPO terms (HPO stands for Human Phenotype Ontology – this uses standard terms to describe humans all over the world, so we can compare you and your genome more accurately against other people).

This information is submitted by the clinical team (doctor, nurse or genetic counsellor) who recruited you onto the Project. It gives us clues about which genes to look at first. We also look at your NHS health records for more clues, and these are updated on our system regularly – so if you have developed new symptoms since you signed up for the Project, we should be able to consider them too.

The more clinical information we receive from your clinical team, the better chance we will have of finding answers about your condition. Genomics England makes available the initial analysis data (called ‘tiered variants’) from your genome to your clinical team so they can also review the data themselves if they want to.

Genomics England works with the NHS to analyse your information and reports it back to your local team. It would not be right for us to cut your doctors out of that conversation, to liaise directly with you. Any findings then need to be assessed by the local hospital laboratory before your doctors can feed back to you.

We intend to revisit everybody’s data at least once using the latest information and diagnostic tools in search of an answer for you. There are also thousands of researchers around the world, led by doctors across the UK, who are now working in our database on specific areas of medicine – they may also find answers for you in the future. If they do, we will tell your local doctors. As with all research findings, these then need to be assessed by the local hospital laboratory before your doctors can return any findings.

At the moment, around 20%–25% of participants are receiving an initial diagnosis (1 in 4, or 1 or 5 of families). We will continue to research the 75%–80% of participants who receive an initial result in which no diagnosis has been found (a ‘negative result’). For some people, this is because the gene which has caused their disorder has not yet been discovered. For some people, it may be because the type of genetic variant causing their disorder is complex, or because there is more than one gene causing the problem, and more work needs to be done to find them.

Compared to standard NHS genetic tests, we’ve already been able to find answers for more people. For example, we have used whole genome sequencing to find a diagnosis for nearly 40% of children who are on this Project because of an intellectual disability, compared to an average diagnosis rate of 18% for those using microarray testing in the past. And we will continue to get better at finding answers for you, as technology improves and we all learn more about different parts of your genome really do.

Genomics England owns the data after it has been donated by participants with their generous consent to its use for research purposes.

But in the sense that participants can withdraw their consent to use of their data at any time, it belongs to the participants.

We are keeping all the panels up-to-date used in both the 100,000 Genomes Project and for the NHS Genomic Medicine Service.

PanelApp is being used as the tool to store and collect information about genes and panels for the NHS Genomic Medicine Service (GMS), as well as for continuing analysis in the 100,000 Genomes Project. Some panels being used for the NHS GMS are the same as those used for genome interpretation for participants of the project. Others have been developed afresh for the NHS GMS. This is because the range of disorders which will be available to test in the NHS (outlined in the Test Directory) isn’t quite the same as the disorders that were investigated in the project.

We are reanalysing the whole genomes of participants. We will look at adding new panels to your reanalysis if there have been major changes in your condition. Even if we use the same panels, they will have been updated if there are newly discovered genes. We now have a field called ‘Panel type’ on each panel page within PanelApp, which indicates what the gene panel is for. Panels with ‘GMS…’ in this field will be used for a clinical indication in the NHS Genomic Medicine Service, while panels with ‘Rare Disease 100K’ or ‘Cancer Germline 100k’ are for project participants. Some panels will have both, for example the intellectual disability panel.

The curation team at Genomics England is continuing to support updates to panels for the NHS GMS and in the project. The aim is to use the same expertise and evidence to keep them all updated together. External reviews help with this effort – we encourage experts to add new publications or new genes to panels, and the curation team review the ‘Activity’ page for new reviews each week. You can view the Activity page to see changes we are making.

Genome reanalysis may happen for a number of reasons. Sometimes a researcher or the Genomics England bioinformatics team will find a new diagnosis while analysing particular groups of genomes. Sometimes a person’s medical condition may change and their doctor may want to take another look at their genome data with the new information.

Genomics England is aiming to reanalyse everyone’s genome data once we have returned everyone’s initial result to the NHS. This will mean all participants benefit from the learning that has taken place during the project. At the moment we are still working on getting a preliminary result back to everyone, so the timing of reanalysis for any particular patient is not yet possible to predict.

You can withdraw from the 100,000 Genomes Project at any time, for yourself, your child, or someone you are a consultee for. Please download the appropriate form below, which you should return to the clinical team of the person who is being withdrawn.

Download form to withdraw yourself or your child (form 6a)

Download form to withdraw as a consultee for someone else (form 6b)

More guidance on withdrawal can be found on each form.

Frequently Asked Questions:
Focused on areas where healthcare and research interact

This information covers similar topics to the FAQs for researchers (which can be found here); the aim of these is to help researchers and clinical teams works together, to maximise benefit for participants, advance knowledge and contribute to the wider genomics community.

Please note that where we have used me and my in the text this also refers to my child where appropriate.

The clinical-research interface describes the interactions and overlap between healthcare and research. By helping doctors and researchers share ideas, we hope to increase diagnoses and research opportunities for our participants and expand genomic knowledge.

You will be contacted by your clinical team; this can include doctors, nurses and genetic counsellors. There are 3 main reasons why your clinical team may contact you.

(i) Your clinical team will contact you if there is a new result for you. The first analysis of your data may have given you a confirmed diagnosis, a partial explanation, or may not have identified any causative variants. Results may also come from subsequent analyses of the data. This can happen for several reasons; for example, because new information has come to light and your clinical team has requested a new analysis, or a researcher has identified a genetic variant that might be causing your health condition and your clinical team agree that this is relevant for you. Please see Question 3 for further information about potentially diagnostic variants identified by researchers.

(ii) Your clinical team may also contact you if a researcher would like to work with them and needs further information that may be helpful for interpreting your genome data, or if they would like to publish their findings in a medical journal. If your clinical team think this may be helpful and further information is required beyond the original consent that you gave for research (for the 100,000 Genomes Project or within the Genomic Medicine Service), they will contact you to ask for your permission.

(iii) Your clinical team may also contact you if they find a clinical trial or patient registry you may be eligible for. They will give you information and discuss whether you may be interested in pursuing this. A clinical trial is usually designed to test the effectiveness of a new medication or other treatment option. A patient registry collects information, and may include an observational study, to learn more about a condition and any changes over time.

In most cases, the reasons for contacting you will relate to the reason you had genetic testing. Participants who consented for research (which includes all who are in the 100,000 Genomes Project), may also be contacted about a clinical study that is relevant for other symptoms they have developed or another condition they have been diagnosed with, that appears in the longitudinal healthcare data we receive over time. For example, if you were in the 100,000 Genomes Project because of a cancer, but later develop a problem with your vision, we may contact your clinical team if there is a clinical trial for a new eye treatment that you could be eligible for.

Related FAQs: Questions 3, 4 and 5

If a researcher thinks they have identified a variant in your genome data that may be diagnostic, they complete a form which is sent to Genomics England for review. This includes information about why the researcher thinks the variant(s) may be causative and evidence to support this from the medical literature.

The Genomics England clinical team will review the information and assess various aspects to help inform the best next step, such as how relevant the variant is to the clinical diagnosis or symptoms.

Those variants that meet criteria for being good candidate causative variants will be returned to the clinical laboratories. NHS clinical scientists will do a formal assessment of the variant(s) and where appropriate will re-issue the diagnostic report and your clinical team will share the result with you. It is very important that researcher-identified variants go through this rigorous assessment process to ensure they are of the clinical standard expected in healthcare.

Variants may also be identified by other means, such as through pipeline improvements and technologies being tested by the Genomics England Bioinformatics and Research & Development team. We will also return these results through an equivalent mechanism to participants’ clinical teams.

We will only contact clinicians whose patients have consented to be contacted; in some cases, we may therefore be unable to feed results back. All the participants within the 100,000 Genomes Project and those who have consented for research through the Genomic Medicine Service, have consented to be contacted unless they have subsequently withdrawn their consent.

Some researcher-identified findings may not relate to the primary reason for which genetic testing was done; in this case they will be processed within the Genomics England Additional Findings workstream. While many participants will have consented to receive additional findings, others have not consented, and it is of utmost importance that we follow participants’ wishes.

Related FAQs: Questions 2 and 4

A researcher can ask us to contact your clinical team, with a request for a collaboration. If your doctor wishes to pursue this and further information is needed beyond the scope of the original consent that you gave for research, they will contact you to discuss. If you agree to participate they will ask for your consent to share information with the researcher and / or for another sample. It may be that there is additional information in your medical record that is helpful for interpreting a genomic variant. In some cases where additional testing is required, your clinical team may be able to send stored DNA from the clinical lab. In other cases, they may need a fresh sample.

Some researchers may want to look further at many different people’s data. In such cases we may need to discuss with the NHS and external groups to seek their support for bigger projects.

Sometimes researchers may apply to us for permission to use spare portions of the blood or tissue samples that you gave us when you had your genome sequenced. Priority will be given to studies that are most likely to yield diagnostic results for participants, are most likely to benefit the genomics community, are larger scale (and therefore using lots of stored samples is beneficial), and those where the Genomics England Research & Development team are assessing new technologies and techniques for interpreting genome data.

Related FAQs: Questions 3 and 5

Yes. There are two ways this may happen.

A researcher (or group of researchers) may ask your clinical team to collaborate to investigate your results further. For example, they may need further information from your clinical team to help confirm or refute a potential diagnosis.

It is also possible for your doctor to make a request for a specific researcher to study your data. For example, if they know the researcher has expertise in a condition or set of symptoms and they think there is a high chance of an underlying genetic disorder. This might also be helpful, for example if there is a variant of uncertain significance and there is a researcher who could help, either by providing their expert opinion or by being able to pursue this further with functional testing in their research lab. The researcher must have access to the Genomics England Research Environment and we cannot guarantee that a researcher will be able to help. We are working to improve this facility, as we think it is helpful to have a two-way flow of information, that can be initiated by both researchers and clinicians.

Related FAQ: Question 4 and 7

Yes. Genomics England expects researchers working on the data from the 100,000 Genomes Project to work with Project Participants. To support this, we fund one patient and participant involvement (PPI) representative for each research domain. You can read the full role profile and responsibilities of a PPI representative here.

If you are interested in becoming a PPI representative, please email the Research Management Team and the domain lead for the research are you’re interested in joining.

Researchers who want to publish in the medical literature using data from the Library (National Genomic Research Library) must make an Airlock application to extract selected de-identified data. Applications are reviewed to make sure that the data cannot be used to identify you. This secure process enables researchers’ findings to be shared to facilitate research and the communication of new findings, without revealing the identity of participants.

Sometimes a researcher may wish to contact a clinician to collaborate on a publication for the medical literature, where it will be helpful to have additional information (beyond the research consent you have already given). If your doctor wishes to pursue this, they will contact you to discuss and if you agree will ask for your consent to share information with the researcher.

Finally, your doctor may wish to publish a report in the medical literature, based on the data available to them within your medical record. They will discuss with you and ask for your consent for publication.

No. Data within the Library (National Genomics Research Library) is de-identified and researchers with access to the Genomics England Research Environment are not allowed to attempt to re-identify any participants.

There are specific circumstances in which researchers can contact Genomics England with information that may be relevant to participants and where appropriate we will contact the relevant clinical teams. For example, if a researcher thinks they have found a potentially diagnostic variant; if we are asked to help identify participants who may be eligible for a clinical trial or patient registry; or if a researcher would like to collaborate with a clinician to help make a diagnosis and / or write a publication for the medical literature. In all cases we will contact your clinical team, who will be best placed to assess and discuss with you. We will not provide identifying details to researchers.

Your doctor may also ask us to pass on a request to a specific researcher, where they feel they will be well placed to give an expert opinion on your genome data. In this case we will flag your genome data to the researcher within the Genomics England Research Environment but will not share identifying details with the researcher. Your clinical team may also wish to ask another doctor, who is also a researcher, for their opinion. In this case, they are doing this to help with your clinical care and the request and opinion are happening outside of the Genomics England Research Environment and within the Healthcare system, and they will need to follow the appropriate governance rules for the sharing of clinical data.

Related FAQs: Question 7

If new information has come to light it is important that you update your clinical team if they are not yet aware. If you are under several different medical teams or if your doctors change, it is important that your main clinical team and / or your genetics team are aware of important updates. Having up-to-date information is helpful both for the primary analysis and whenever there is a re-interpretation of the genome data.

For participants consented for research (this includes all those within the 100,000 Genomes Project), we also receive longitudinal healthcare data, which is available in a de-identified form to researchers within the Genomics England Research Environment.

Whilst some people may have the same doctor for many years, it is not uncommon to be under the care of different clinical teams and for this to change over time. For potentially diagnostic variants identified by researchers, we will usually be contacting the relevant Genomic Laboratory Hub (GLH) who will re-issue the diagnostic report if appropriate. They will make sure that when a diagnostic report is re-issued that it is sent to an appropriate clinical team. In some cases we may write directly to a clinician, for example to pass on requests for collaborations from researchers.

Useful information

Genome Analysis

Find out how its done.

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Results

Latest updates for participants.

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Genome analysis and results

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