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SNP coverage analysis/comparisons (23andme v3/v4, AncestryDNA, FTDNA) (self.23andme)

submitted by firemylasers

I ran some analysis on what SNPs are covered by 23andme v3, 23andme v4, AncestryDNA, and FTDNA (better known as Family Tree DNA).

The genomes used were public with the exception of the v4 file, for which I used my own. The v4 file and the AncestryDNA files were created within the last few months, the v3 file is from maybe 2012, and I think the FTDNA file is also from the past few months. I won't disclose the source I used, but it is publicly accessible and can be easily found if you have a burning desire to look at other people's genetic data.

The number of SNPs (including the limited number of items without the Rs prefix) in each file is:

Analyzed file Number of SNPs
23andme v3 991,624
23andme v4 598,897
AncestryDNA 701,478
FTDNA 693,719

This information isn't very useful like this, but the next part is. After enough data manipulation and comparison, I was able to determine how many SNPs from each file were covered. I think the table below presents this information pretty well:

Comparison file Primary file Number unique to Primary
23andme v3 23andme v4 71,570
23andme v4 23andme v3 464,297
AncestryDNA 23andme v4 291,416
23andme v4 AncestryDNA 393,997
FTDNA 23andme v4 296,302
23andme v4 FTDNA 391,124
FTDNA AncestryDNA 30,983
AncestryDNA FTDNA 23,224

The way this works is that the number unique to the primary file is the number of SNPs present in the primary file but NOT present in the comparison file, or the number unique to the primary (within the comparison of course). Since I ran this in several ways, you can infer a lot of useful info from this. Make sure not to confuse the order -- if the data is "A B 123", it means that B has 123 SNPs that A does not have, not the other way around. But if it's "B A 227", that means that A has 227 SNPs that B does not have. Keep in mind that this can be misleading if you don't realize the unique SNPs reported are in a different file for both examples, and that this can also be used to identity the number of shared SNPs using the totals reported in the first table.

I have extensively verified these results, so they should be accurate. I did do some additional analysis, but most of it is not as interesting as this stuff is and I'm not as confident about the results from that stuff.

So, what does this tell us? Well, the results confirm that 23andme v4 did loose a large number of SNPs vs v3, but it also tells us that 23andme v4 added only 71.5k new SNPs over v3 while loosing 464k SNPs, which is much more informative than the raw net loss of 392,727 SNPs. You can also see that while AncestryDNA and FTDNA can give you around 100k more total SNPs than 23andme, there are still over 290k SNPs that can only be obtained via 23andme's chip, and so each can only give you around 305k of the SNPs present on 23andme's chip. And yes, those 290k SNPs include many many many important medically-relevant SNPs that are NOT reported by FTDNA/AncestryDNA.

You can also see that there are potentially significant differences between the SNPs reported by AncestryDNA and FTDNA despite both using extremely similar chips. FTDNA is of course known for scrubbing certain info from their raw data, including a chunk of medically-relevant SNPs.

Some of the additional analysis I ran looked at AncestryDNA/FTDNA vs v3, but I'd need to rerun that and verify it before reporting those results. I also looked at how many unique genes you get from combining different tests, but the same issues apply to that (and it is a bit misleading because of differing genes covered with differing combinations). I can go redo it if it's wanted, but those results weren't that useful. I can summarize that analysis as: while combining tests will give you more SNPs, you won't be getting much useful information out of it (at least if you're looking for health-related SNPs).

Part of my reason for doing this analysis was to see if it'd be worth paying for additional tests, which I'd consider justifiable if I was getting a bunch of useful SNPs, but the results convinced me that it was not worth it. If you don't care about health and just want as many SNPs as possible for some odd reason, you can get over a million unique SNPs in total by combining v4/FTDNA/AncestryDNA (or just a bit under a million with only one of them added to v4), but it is almost utterly pointless, I'd far rather wait to spend the money on exome sequencing once the price drops low enough (or even just on an upgrade to 23andme v5 whenever that gets released).

I hope this was interesting!

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[–]trillskill 2 points3 points  (4 children)

Hey I just wanted to say thanks for the awesome analysis, this is very useful for people deciding on whether it is worth it for them to explore additional testing. Did you ever get around top comparing 23andMe v3 to FTDNA and/or AncestryDNA? I've been considering getting genotyped by FTDNA but I didn't know whether or not it would be worth it considering I had chip v3 results.

[–]firemylasers[S] 1 point2 points  (3 children)

v3 + FTDNA => +14,500 SNPs vs v3 alone

v3 + AncestryDNA => +13,500 SNPs vs v3 alone

I suggest v3 + v4 => +71,570 SNPs vs v3 alone (and much more medically interesting SNPs here)

[–]trillskill 0 points1 point  (2 children)

How would I get v4 data? Was it given automatically to v3 users? I know 23andMe let users choose to upgrade from v2 to v3 a while back but I don't recall anything allowing v3 users to get v4 data.

[–]firemylasers[S] 2 points3 points  (0 children)

I'm not sure if they allow the direct upgrade from stored samples that they did in the past. They actually don't recommend v3 to v4 upgrades because they don't change health/ancestry reports significantly. You can still reorder the test though to get v4 raw data, but IDK if it'll offer you something worth the price for your particular use case.

I've noticed some interesting recent tidbits from 23andme that loosely suggest a possible chip change may be coming. There's nothing concrete though -- it could be something else entirely that's happening.

[–]firemylasers[S] 2 points3 points  (0 children)

Okay so based on past release patterns the v5 chip may possibly be coming in November 2015, but it could be November 2016 instead (and IMO there's a good chance of that). They may be announcing something related to readding health reports for US customers soon, although I'm a bit skeptical of that. They raised another large chunk of money recently, so a November 2016 update seems quite possible.

I'm not sure what the next step will be in terms of chips. They could increase the number of markers by shifting to a lower-density iSelect HD chip, but I can't really see them doing that. I think their next chip update may happen once there's a 24-sample iSelect HD that can handle more than the current 700,000 max SNPs, as currently you need to use a lower-density chip for more than 700k. However, given their endorsement of imputation, it's possible that they may stick with v4 even past November 2016. IMO the company is much more focused on research projects related to their database now, and much less so on their products. 23andMe is doing small-scale runs of higher-end sequencing technologies for some of their research, but outside of that, you can't get it anytime soon (see below).

Whole-genome sequencing won't be coming for a long time, and exomic sequencing is still far too expensive for 23andMe's price point. Exome is definitely not happening within the next revision or two of the chip unless they decide to eat a LOT of the costs and/or raise their price significantly.

IDK, it's hard to see what the next step forward will be. Maybe Illumina will release something interesting soon, I know 23andMe works closely enough with them that they'd likely have access to unreleased stuff, so nobody really knows what's possible there. I know that they'll eagerly deploy exome sequencing once it eventually becomes cheap enough to use, but that's not really soon at all. Their current chip can get some exomic markers and CNVs, which is rather interesting, but they're still limited by the 700k max SNPs on their current 24-plate custom chips.

Unfortunately as all of these chips are for research use only, it is next to impossible to get them directly -- you basically have to go through 23andMe, FTDNA, or AncestryDNA if you want results, and then you're limited to only either the OmniExpress's 700k SNPs, or 23andMe's 600k custom SNPs (which are clearly superior for medical purposes)...

Maybe 23andMe will look into offering pharmacogenetic testing via clinicians. Lots of money to be made there...

Or maybe they'll just focus on research using their existing DB. One million samples is a fucking insanely large DB, and they can pick any samples to resequence using exome or whole-genome sequencing (which can be done with screening for certain SNPs to identify study populations!) -- they have so many samples of DNA sitting around, can you even imagine having over a million archived samples of DNA?

[–]Cosmotropics 2 points3 points  (3 children)

For someone who is more interested in the medical/health e.g. aspects in the data is the v4 a big no-no compared to v3?

[–]ChaoticGoodBrewing 2 points3 points  (1 child)

So it appears after reading this 23andMe blog entry that they planned on switching to the V4 chip regardless of the FDA health issue. http://blog.23andme.com/news/23andmes-new-custom-chip/

The part that stuck out to me was:

"...The selection was made to maximize the number of actionable health and ancestry features available to customers as well as offer flexibility for future research."

So I'm optimistic that the V4 hopefully is better.

[–]Cosmotropics 1 point2 points  (0 children)

Yes let us hope so! Now that you mention it, I think I may have stumbled upon that post before, but I was conflicted as to whether or not to believe it, seeing as so many people argued that the V3 was simply better due to it's sheer number of SNPs.

At any rate, I will be doing the V4 soon, as there aren't really that many options. I'm quite fresh at this, but I think I will just use Promethease and see what pops up on health/personality.

[–]firemylasers[S] 1 point2 points  (0 children)

That's hard to say, see my previous reply:

They actually don't recommend v3 to v4 upgrades because they don't change health/ancestry reports significantly. You can still reorder the test though to get v4 raw data, but IDK if it'll offer you something worth the price for your particular use case.

[–]Equivalent_Alps_8321 1 point2 points  (0 children)

v5 update?