Wednesday 9 August 2017

23andMe launch a new v5 chip and revise their health and trait offerings in the UK

23andMe have quietly rolled out their new v5 chip. There has not so far been any official announcement from 23andMe, though the news was confirmed yesterday by a moderator in the 23andMe Forums. We believe 23andMe are now using Illumina's new Global Screening Array chip which is already being used by Living DNA. 23andMe were one of the 12 customers who signed up to the GSA in June 2016. They also belong to the Global Screening Array Consortium.

The GSA has 640,000 markers and the ability to include up to 50,000 custom markers. Here is a description of the chip from Illumina:
The Infinium Global Screening Array-24 v1.0 BeadChip combines multi-ethnic genome-wide content, curated clinical research variants, and quality control (QC) markers for precision medicine research. 
The genome-wide content was selected for high imputation accuracy at minor allele frequencies of >1% across all 26 1000 Genomes Project populations. The clinical research content includes variants with established disease associations, relevant pharmacogenomics markers, and curated exonic content based on ClinVar, NHGRI, PharmGKB, and ExAC databases. Quality control content enables sample identification and tracking for large-scale genomics and screening applications.
The full technical specifications for the GSA chip can be found here on the Illumina website.

The Illumina Omniexpress chip, which was previously used by all the genetic genealogy companies, is being phased out, so we are likely to see other companies moving to the GSA in due course. The OmniExpress worked well for European populations but was not so good for other populations. The GSA provides much better global coverage and should improve the results for people with non-European ancestry.

The GSA is designed for imputation. Imputation is the process of inferring the missing markers in a DNA sequence. This can be done by statistical methods because DNA is passed on in chunks, which means that markers travel together. Researchers can use imputation to reconstruct an entire genome sequence, and it provides a much more cost-efficient way of doing large-scale studies. However, I know of no scientific papers which have looked at the efficacy of imputation for cousin matching. The companies will have a significant challenge ahead in the months to come as they adapt to the new chip and test out their imputation pipelines.

Because there are so few overlapping markers between the GSA and the OmniExpress this change will also present problems for companies and third-party websites that accept autosomal DNA transfers. A choice will need to be made as to whether to do comparisons using only the overlapping markers or whether to experiment with imputation. GEDmatch is already experimenting with its new Genesis database, which can now accept GSA transfers. It will be interesting to see what solutions are found by other companies.

Along with the move to the new chip, 23andMe have also changed their product offering in the UK. There has not been any official announcement but as far as I can establish from the archived versions of their British website in the Internet Archive the changeover seems to have occurred some time towards the beginning of May. When the website was archived on 29th April 23andMe were still offering UK customers 100 health and trait reports. They offered 40+ reports for inherited conditions, 40+ drug response reports, 10+ genetic risk factor reports and 40+ trait reports. The genetic risk factor reports including reports for haemophilia and some breast cancer genes (BRCA1 and BRCA 2). A full list of the previously offered health reports can be seen here.
The 23andMe GB home page on 29th April 2107.
The next archived version of the 23andMe GB website dates from 6 May 2017. From that date onwards UK customers have been offered a very much reduced range of health reports. There are now 40+ carrier status reports, 3+ genetic risk reports and 25+ traits and wellness reports. The drug response reports are no longer provided at all, and the breast cancer and haemophilia reports have been dropped. A full list of the new reports offered can be found here. As far as I can establish UK customers now receive exactly the same version of the test as customers in the US, the only difference being that we do not have an option to order an ancestry-only version of the test for half the price.
The 23andMe GB home page on 9th August 2017.

23andMe have slowly been moving their customers over to their new website (otherwise known as The New Experience or TNE for short). My accounts were finally transitioned on 15th June 2017. I understand that all the UK accounts were transitioned at the same time. I believe the transition process is now complete, with the Canadians appearing to be the last people to be transitioned in July.

With the transfer to the new website all our old health reports have been archived. There are no new health reports. Instead there are five ancestry reports, 19 trait reports and 7 "wellness" reports.

I was on holiday in the US when I was transitioned and I initially assumed that the lack of new health reports was because I was accessing the website from the US and not the UK. However, I later established that none of the transitioned accounts in the UK were receiving any new health reports. I wrote to 23andMe customer service to find out why this was the case and received the following message on 10th July:
Per FDA restrictions, newly authorized reports will not be provided to customers genotyped on your current chip version. The conditions covered by our newly authorized reports are addressed by reports in your Reports Archive.

In order to receive the newly authorized reports, you will need to be genotyped again. Upgrades are unavailable at this time. We are currently working on an upgrade policy for our customers and would encourage you to wait for this policy to be finalized. The upgrade policy will allow you to be genotyped on our most up-to-date chip at a discounted rate within the next few months. More information about upgrades will be available soon.
My guess is that 23andMe customers in the UK have been tested on the new v5 chip from May 2017 onwards when the website changed and the number of reports was reduced.

23andMe received authorisation from the FDA in April this year to start offering genetic health risk reports for 10 diseases and conditions. No doubt they are also working towards approval for introducing other reports too. Clearly, in order to get the FDA approval, the reports will need to be validated on the new v5 chip and it's no longer worth their while trying to update and validate the old-style health reports. I can therefore understand the decision to stop offering these reports to existing customers.

tested with 23andMe back in 2010 on the v2 chip. I've never had to pay a subscription or pay for any updates so I've had very good value for money in the last seven years. I will be upgrading to the new chip when it becomes available to existing customers and I shall look forward to receiving all the new reports as and when they become available.

Update 10th August 2017
It has been confirmed in a post by a moderator in the 23andMe Forum that 23andMe are now using the Illumina Global Screening Array. They suggest that with an upgrade to the new chip: “Results shouldn’t change significantly, however, there may be some slight differences in Ancestry Composition, DNA Relatives, and small changes in your haplogroup assignment.”

We are told that 23andMe have updated their phasing algorithms so that “family members can still be phased, even if they are on different chips”.

It appears that the transition to the v5 chip is not yet complete. Here is a further quote from the moderator: “Our labs are currently transitioning to the v5 chip. While transitioning, there may be some overlap between v4 and v5 data being released. Future customers will be genotyped on v5.”


hallwal said...

Interesting. This massive shift, involving few overlapping SNPs with old versions, seems rather terrifying as it potentially alienates all autosomal DNA results in all currently existing databases. Many of the most valuable DNA kits in those databases came from now deceased individuals. The vast majority of others will not be DNA geeks like us and retest on the new chips. This means a vast generation of immensely valuable DNA results may be lost forever, which would be heartbreaking.

hallwal said...

On a lighter note, an admittedly selfish question: If this change is intended to improve results for non-European populations, does that mean it will slightly lessen the quality of the results for European populations?

Debbie Kennett said...

In theory it should be possible to impute the missing markers so that old kits are compatible with the new v5 chip. Much will depend on the quality of the imputation at the different companies. 23andMe have a large database of over two million people so hopefully that will allow them to do a good job of the imputation.

I don't know how this change will affect Ancestry Composition results for Europeans. Let's hope the new chip will improve results for everyone!

The Lost Guide said...

As far as the mtdna portion of the chip, SNPs for 973 loci have been deleted in v5 vs v3 and 961 have been added. I don't see any obvious pattern (e.g. more New World or Asian haplogroup coverage at the expense of European). However in the case of my interest, Haplogroup W, it is devestating; 26 loci informative in placing a person on the tree have been removed, and the 12 new ones added are not very useful. This includes mutations that define major subgroups. The mutation for subgroup HV has been deleted as well, which means this major group is now classified as 'R0'. This all will undoubtedly cause a lot of consternation when users get results showing mtdna haplogroups different from their siblings or mothers! Don't know the rhyme or reason for this, but it means 23andme results have become all but useless for me in analyzing Haplogroup W or HV placements... Pausanias, Haplogroup W Website

Debbie Kennett said...

That would indeed be a shame. Are all the mtDNA SNPs actually working properly yet? I know there have been a few teething problems with the new GSA chip.

Daiko said...

You could just go to FTDNA and do a FULL MTDNA SEQUENCE for $200, if you really want to have a deep understanding of your MTDNA