Additional findings

As part of participants’ consent for the 100,000 Genomes Project, they were asked if they wanted us to look for additional health information in their genome sequence; we call these ‘additional findings’. Additional findings are not related to the main reason why participants were recruited to the Project.

We are now ready to return the additional findings results and we are working together with the NHS on how we will share them with our participants.

Participants will now have the opportunity to check whether they have consented to receiving additional findings results, and to let us know if they’ve changed their minds. Click here to find out more about the ‘Check My Choices’ portal.

Our additional findings analysis will focus on looking for gene alterations or ‘spelling mistakes’ in a specific list of genes that may increase the risk of people developing certain health conditions. We chose this list because, if someone has an alteration in one of these genes, then they may have an increased risk of developing disease. If you have an alteration, it does not mean that you will [definitely] get that condition. This is a very important point to understand. Instead, health professionals believe there may be an increased chance and steps can be taken to reduce the likelihood of the associated health condition developing the associated health condition, or the condition can be treated or monitored.

The full list of genes and the health conditions associated with them can be found below. These gene alterations are rare, and about 1 in 100 participants who consented to additional findings in the 100,000 Genomes Project will have one of these findings.

What is looked for in adults and what is looked for in children

Only alterations in genes that cause childhood-onset disease will be looked for in child participants. This is in line with national policy on ‘The genetic testing of children (second edition) 2010’.

Some participants, who joined the 100,000 Genomes Project as children, have now reached the age of 16. This means that they will need to be asked again – as adults – whether they consent to continue in the Project or not. The NHS and Genomics England have been, and still are, contacting these young adults and their parents/guardians.

For any participants who opted in for additional findings when they were a child but have not re-consented as an adult, we will only report back results from the list of children’s gene alterations. Anyone in this situation who wants to re-consent as an adult participant should contact the clinical team who recruited them onto the 100,000 Genomes Project. If you are not sure how to contact the relevant clinical team, please get in touch with our Service Desk team on 0808 2819 535.

Timelines

We would like to apologise for the long wait that all participants who have consented to receiving additional findings results have had to endure so far. This has been a massive undertaking between Genomics England and NHS England, and we really appreciate your patience and understanding.

Additional findings results will start to be returned to NHS genomic laboratories from Spring 2021. All of the results will have been returned to the NHS by December 2021, so participants should expect to hear back between Spring 2021 and the start of 2022. We will be analysing and reporting back the results in batches over this time period, so as not to overwhelm the laboratories. Everyone who has provided consent for the additional findings to be looked at will get a result, even if no gene alterations on the list above are found.

We’re drawing this to your attention because we don’t want you to worry that you’ve been forgotten, or if a friend or family member receives their results before you.

Checking your choice for additional findings analysis and changing your decision

We only look for these gene alterations if a participant has told us that they want us to do this. Participants can change their mind about whether they want to receive these additional findings results at any time.

 Use the Check My Choice portal 

If you’ve forgotten whether you asked for additional findings or not, you can use the ‘Check my Choices’ portal to see what you agreed. The portal is managed by Genomics England and is secure. If you use our portal, we will use your details to look at the permissions you have given us. You can also use the Genomics England secure portal to change your choice at any time.

If you are not able to use the portal, you can also call the Genomics England Service Desk to check or change your choice on 0808 2819 535.

The deadline for the second batch of additional findings analysis is Monday 5 July 2021.

If you change your choice from ‘no’ to ‘yes’ and you miss the deadline for a batch, your analysis will be done in a subsequent batch.

We will start analysing results in April, so if you change your choice from ‘yes’ to ‘no’ after this, the system may still put you through for analysis. We will notify the genetic services that you have changed your mind, but it may be that they have already completed the analysis and are in the process of returning your result to you. In this case you may still receive a result.

Results

As the gene alterations we are looking for are rare, most people will not have an additional finding identified.

Unlike the primary findings where results were only returned for the person with the condition, so there was one result per family, for additional findings each participant who consented for additional findings will receive their own letter with their result.

Receiving results

All participants who have consented to additional findings results will receive a letter from one of the NHS Genomic Medicine Service Alliances, whether we have found a gene alteration (a ‘positive’ result) or not (a ‘negative’ result). The regional NHS Genomic Medicine Service Alliances have replaced the NHS Genomic Medicine Centres from the 100,000 Genomes Project.

If you receive a positive result for additional findings, please don’t assume this means you have one of the health conditions that are associated with the genes we have looked at. What we will have found is a gene alteration which may indicate that you are more likely to develop one of these health conditions. You will be invited to schedule an appointment with an NHS clinician, where you will be able to discuss the additional findings result, what this means for you, and any next steps. Individual details cannot be discussed outside of your appointment.

If you receive a negative result for additional findings, this means we have not found any gene alterations that may increase the likelihood of you developing the health conditions in our list, but this does not mean that you will never develop them. At this time, with the scientific knowledge we have available, no gene alteration which may increase the likelihood of you developing the health conditions in our list has been found in you, but other gene alterations might be discovered in the future.

Additional findings conditions and genes

The following conditions will be looked for as part of the additional findings analysis.

Adults only

Genes: MLH1, MSH2, MSH6

Changes in these genes increase the risk of developing various cancers, most commonly bowel, womb and ovarian. Approximately 1 in 200 people in the general population have one of these gene alterations.

There are other genes that are linked to a risk of bowel cancer that we won’t be looking for.

For more information on genetic causes of bowel cancer and Lynch syndrome, visit the Bowel Cancer UK website or the Genomics Education Programme, part of Health Education England, website.

Genes: MUTYH, APC

Changes in these genes increase the risk of developing bowel polyps and cancer.

For more information on genetic causes of bowel cancer and Lynch syndrome, visit the Bowel Cancer UK website or the Genomics Education Programme website.

Genes: BRCA1, BRCA2

Alterations in the two BRCA genes have been shown to increase the risk of breast cancer, as well as ovarian cancer and prostate cancer. These changes have a 50% chance of being inherited from parent to child. For more information about the BRCA genes, visit the Macmillan website or the Genomics Education Programme website (BRCA1 and BRCA2).

Genes: VHL, MEN1, RET

Von Hippel-Lindau disease is a rare condition caused by changes in the VHL gene that affects 1 in 36,000 births. Parents with Von Hippel-Lindau disease have a 50% chance of passing it down to their children. Von Hippel-Lindau disease can present with lots of different complications and at various ages, even within the same family. Find out more about Von Hippel-Lindau disease from VHL UK/Ireland’s website or the Genomics Education Programme website.

Multiple endocrine neoplasia type 1 (MEN1) is a condition, caused by changes in the MEN1 gene, that can lead to tumours growing in the endocrine glands. Most people inherit the mutated MEN1 gene from a parent, and there is a 50% chance of a parent passing it down to their children. More information about MEN1 can be found on the Association for Multiple Endocrine Neoplasia Disorders (AMEND) website, Macmillan’s website, or the Genomics Education Programme website.

Changes in the RET gene significantly increases the risk in medullary thyroid cancer. Parents with an altered RET gene have a 50% chance of passing this down to their children. For more information, visit the Genomics Education Programme website.

Genes: LDLR, APOB, PCSK9

Familial hypercholesterolaemia is a condition that causes high cholesterol, which can lead to early heart attacks and heart disease. Changes in any of the three genes we are looking for can cause familial hypercholesterolaemia because they remove cholesterol from the blood. People who have changes in one of these genes have a 50% chance of passing it down to their children. Find out more about familial hypercholesterolaemia and high cholesterol on the British Heart Foundation website, Heart UK’s website, or the Genomics Education Programme website.

Some gene alterations have no effect on the individual who has them, but may affect future children. If someone has such an alteration, they are said to be a ‘carrier’. At the moment we are only looking for one of these conditions – cystic fibrosis. For a child to have this condition both parents will be carriers. We will therefore only look for alterations in the cystic fibrosis gene if both partners in a couple took part in the Project and both asked us to look for this.

Gene: CFTR

Cystic fibrosis is an inherited condition caused by changes in the CFTR gene, and affects 1 in 2,000 to 1 in 3,000 babies of Northern European ancestry. It is less common in other ethnic groups. Between 1 in 22 and 1 in 27 people in the UK are carriers. Read more about cystic fibrosis on the Genomics Education Programme website.

Adults and children

For children whose parents have asked for additional findings, we are looking at a very small number of genes where there is something that could be done to prevent illness in a child.

Gene: APC

Changes in this gene increases the risk of developing bowel polyps and cancer.

For more information on genetic causes of bowel cancer and Lynch syndrome, visit the Bowel Cancer UK website or the Genomics Education Programme website.

Genes: VHL, MEN1, RET

Von Hippel-Lindau disease is a rare condition caused by changes in the VHL gene that affects 1 in 36,000 births. Find out more about Von Hippel-Lindau disease from VHL UK/Ireland’s website or the Genomics Education Programme website.

Multiple endocrine neoplasia type 1 (MEN1) is a condition, caused by changes in the MEN1 gene, that can lead to tumours growing in the endocrine glands. More information about MEN1 can be found on the Association for Multiple Endocrine Neoplasia Disorders (AMEND) website, Macmillan’s website, or the Genomics Education Programme website.

Changes in the RET gene significantly increases the risk in medullary thyroid cancer. For more information, visit the Genomics Education Programme website.

Genes: LDLR, APOB, PCSK9

Familial hypercholesterolaemia is a condition that causes high cholesterol, which can lead to early heart attacks and heart disease. Changes in any of the three genes we are looking for can cause familial hypercholesterolaemia because they remove cholesterol from the blood. People who have changes in one of these genes have a 50% chance of passing it down to their children. Find out more about familial hypercholesterolaemia and high cholesterol on the British Heart Foundation website, Heart UK’s website, or the Genomics Education Programme website.

FAQs

This section will be regularly updated.

We are really sorry if you have not yet received your main results from the 100,000 Genomes Project. Although we have returned all of our analyses back to the NHS, there is still a big job for clinicians to confirm that our analysis is correct for each patient. The COVID-19 pandemic has also decreased staffing, resourcing and other capacity in the NHS, but we are still working together to try to get all main results back to our participants as quickly as possible.

Additional findings will start to be returned from Spring 2021 and it is expected that all findings have been returned to participants by beginning of 2022.

In our plans for returning carrier findings, the NHS and Genomics England agreed that we would only return a result for conditions caused by a genetic alteration passed from both parents to a child, if both parents were carriers and had agreed to reproductive findings. Cystic fibrosis is the only condition on the list at the moment, and only families where both parents are in the 100,000 Genomes Project and where both agreed to additional findings will be looked at for this.

For more information about each of the conditions we look for in our additional findings analysis, please visit the following links to charities and organisations specialising in those conditions:

Lynch syndrome and bowel cancer:

Breast and ovarian cancer:

Von Hippel-Landau disease:

Multiple endocrine neoplasia type 1 (MEN1):

Familial medullary thyroid cancer:

Familial hypercholesterolaemia:

Cystic fibrosis:

A negative result means we have not found anything in your genome that has strong evidence of causing any of the conditions we’ve looked for. However, please note that this does not mean that you will never develop one of these conditions. If you develop any symptoms you’re worried about, please contact your doctor.

Our additional findings analysis will include participants who have passed away if they had given their consent for this before their passing. Many participants nominated someone to whom results could be returned to in the event that they had died, however not all participants provided us with this information. The NHS Genomic Medicine Service will look at each case on an individual basis to see if they have records that mean they can report the results.

Loading...