Razib Khan One-stop-shopping for all of my content

February 8, 2011

Health care costs and ancestry

Filed under: Ancestry,Genetics,Genomics,Health,Medical Genetics,race — Razib Khan @ 1:07 am

The Pith: In this post I examine the relationship between racial ancestry and cancer mortality risks conditioned on particular courses of treatment. I review research which indicates that the amount of Native American ancestry can be a very important signal as to your response to treatment if you have leukemia, as measured by probability of relapse.

If you are an engaged patient who has been prescribed medication I assume you’ve done your due diligence and double-checked your doctor’s recommendations (no, unfortunately an M.D. does not mean that an individual is omniscient). Several times when I’ve been prescribed a medication I have seen a note about different recommended dosages by race when I did further research. Because of my own personal background I am curious when it says “Asian.” The problem with this term in medical literature is that “Asian” in the American context is derived from a Census category constructed in 1980 for bureaucratic and political purposes. It amalgamates populations which are genetically relatively close, East and Southeast Asians, with more distant ones, South Asians (when my siblings were born I remember that my parents listed their race as “Asian” ...

December 15, 2010

“Genome blogging”

Nature profiles Dodecad, the Pickrell Affair, and the emergence of amateur genomicists in a new piece. Interestingly David of BGA is going to try and get something through peer review. In particular, the relationship of Assyrians and Jews.

So we have Genomes Unzipped, Dodecad, and BGA. What next? Who next? I hope Dienekes doesn’t mind if I divulge the fact that the computational resources needed to utilize ADMIXTURE as he has is within the theoretical capability of everyone reading this post. Rather, the key is getting familiar with PLINK and writing some code to merge data sets. After you do that, to really add value you’d probably want to get raw data from more than what you can find in the HGDP, HapMap and other public resources.

But here I make an open offer: if you start a blog or a project which replicates the methods of Dodecad and BGA I’ll link to you and promote you. When Dienekes began Dodecad I actually started to play around with the data sets in ADMIXTURE, but I’ve personally held off until seeing what he and David find. What their pitfalls and successes might be. Here’s to 2011 being more interesting than we can imagine!

Update: Already had a friend with a computational background contact me about doing something on South Asian genomics. So again: if you get a site/blog set up, and start pumping out plots, I will promote you. In particular, if you need 23andMe raw data files of geographical region X it might be useful to try and get the word out via blogs and what not.

November 23, 2010

Eurogenes 500K SNP BioGeographicAncestry Project

Filed under: Admixture,Ancestry,BGA,Genetics,Genomes Unzipped,Genomics — Razib Khan @ 12:11 am

Since I have been promoting the Dodecad Ancestry Project, it seems only fair to bring to your attention Eurogenes 500K SNP BioGeographicAncestry Project. The sample populations are a bit different from Dodecad, but again ADMIXTURE is the primary tool. But the author also makes recourse to other methodologies to explore more than simply population level variation. For example, his most recent post is Locating and visualizing minority non-European admixtures across our genomes:

Imagine, for example, a white American carrying a couple of tiny segments of West African origin, from an ancestor who lived 250 years ago, and an eastern Finn with no Asian ancestors in the last 4000 years or more. If we run an inter-continental ADMIXTURE analysis with these two, it’s very likely the American will score 100% European, while the eastern Finn will probably come out around 9% North and East Asian due to really old Uralic influence.

That sort of thing isn’t a huge problem when comparing the genetic structure of populations. Obviously, overall, eastern Finns rather than white Americans are genetically closer to North Asians, and that’s basically what ADMIXTURE picks up. However, if the focus is also on individuals, this certainly can become an issue. Our hypothetical American might be aware of that African ancestor, with solid paperwork backing up their genealogical connection, but he’s pulling his hair out because nothing’s showing up via genetic tests.

So let’s take a look at a real life example of how RHHcounter can pick up segments of potentially recent Sub-Saharan African origin…

euras1
Olivia Munn & Uyghur woman

The basic issue here is that in terms of genomic variation old admixture looks different from new admixture. Someone who is a first generation Eurasian, with a Chinese and European parent, may be about the same ancestral mix proportionally as a Uyghur. They would resemble a Uyghur on STRUCTURE and be placed within that cluster on a PCA chart (this is what happens in 23andMe). But, the Uyghur “Eastern” and “Western” genetic heritage has been reshuffled to a great extent by recombination over the past 1,000-2,000 years. In contrast, a first generation Eurasian will have huge swaths of their genome which are Eastern or Western on alternating strands (from their respective parents). In population genetic language a group of first generations hybrids would be exhibit a lot of linkage disequilibrium (LD). In a panmictic hybrid population LD will decay due to recombination, which breaks apart the distinctive allelic associations inherited from the parental populations.


This is the key to differentiating between the old “Asian” ancestry which sometimes falls out of the genetic variation of Finns at low frequencies, and more recent Asian ancestry. For example, the paleoanthropologist Vance Haynes is apparently a great-grandson of one of the original “Siamese Twins,” Chang Bunker. Chang Bunker was a Chinese Thai, so presumably Vance Haynes would come out to be ~10% Asian, and would be shifted toward the Asian cluster in relation to other Europeans. On the other hand, a closer look at his genome would indicate differences from a Turk who was ~10% Asian, because Vance Haynes’ Asian ancestry has only had three generations for recombination to break apart the original allelic associations which were passed down from Chang Bunker. After only these few generations the genome would still show many segments of clustered ancestry with distinctive sets of markers characteristic of Han Chinese.

Let’s make this more concrete. Below are two “ancestry paintings” from 23andMe. One is of a reference example, a Uyghur woman, and another is of a Eurasian individual. The difference is pretty obvious:

eurasianman

23andmeclusFor the record, 23andMe says that the Eurasian man is 50% Asian, 50% European. For the Uyghur woman, 52% European, 48% Asian. As I indicated above, Eurasian individuals who are projected onto the variation of the HGDP sample tend to cluster with the Uyghurs. In the image to the left the black mark indicates the Eurasian man. The Uyghurs are green. The purple rectangles are Hazaras.

But obviously this is a trivial example. What’s the point of sniffing around for non-European ancestry in individuals whose non-European ancestry is 1) visible, and 2) recent and immediate. No, a bigger question here are claims and suggestions by some white Americans that they have significant non-European ancestry. Usually this is Native American. But in the case of one of the European-origin samples which “Polako” (the principal behind the BGA Project) analyzed it seems there is a suggestion of West African ancestry.

dandonThis individual is Dr. Don Conrad of Genomes Unzipped. In particular, Polako found that there were two nearby segments on two chromosomes which exhibited a pattern of population atypical heterozygosity in Dr. Don Conrad’s genome. Look at chromosomes 7 and 13. Contrast the pattern with my distant paternal cousin, Dr. Daniel MacArthur. He also exhibits points of heterozygosity, but they’re randomly distributed across the genome. It’s old admixture or just noise.

Polako doesn’t make much of Dr. Don Conrad’s results, and neither do I (presumably as Dr. Don Conrad is a member of Genomes Unzipped it’s easy to talk about his results without any of the ethical or moral hassles about confidentiality). On the other hand, unlike Dr. Dan MacArthur, a little utilization of the powers of the interwebs indicates that Dr. Don Conrad is an American. In particular, of recent Midwestern background. Though I’m not a total creep, so I didn’t start poking around Ancestry.com. But after the Pickrell affair I am probably just a touch more hesitant to laugh off peculiar results from these sorts of analyses as simply algorithms-gone-meshugana.

Image Credit: Colegota

November 12, 2010

Was the Pocahontas exception necessary?

Filed under: Ancestry,Genetics,Genomics,race — Razib Khan @ 12:11 am

Harry_F._ByrdIn Jonathan Spiro’s Defending the Master Race it is recounted that as American states were passing more robust anti-miscegenation laws and legally enshrining the concept of the one-drop-rule an exception was made in Virginia for those with 1/16th or less Native American ancestry. The reason for this was practical: many of the aristocratic “First Families of Virginia” claimed descent from Pocahontas. Included within this set was Senator Harry F. Byrd Sr. of Virginia, who was 1/16th Native American, being a great-great-grandson of Pocahontas. This sort of background was probably not exceptional among the “Founding Stock” of Anglo-Americans whose ancestors were resident within the boundaries of the American republic at independence. Only around 1700 did the white population of the American British colonies exceed the indigenous, so no doubt some amalgamation did occur.

But from what I’ve seen the extent of admixture with the indigenous substrate was very marginal, especially in comparison to white populations in Argentina or Brazil. Or so I thought. In conversation a friend recently claimed that over 50% of American whites were 5% or more non-European in ancestry. I expressed skepticism, and he dug up the citation. Genetic ancestry: A new look at racial disparities in head and neck cancer:

The study included 358 patients; 37 percent were African American.

The researchers examined diagnosis (late versus early stage) and overall survival for African Americans with HNSCC based on self-reported race and genetic West African ancestry.

During the past decade, many groups have developed and characterized sets of single nucleotide polymorphism markers that can distinguish genetic ancestry among major ethnic groups such as Asian and West African, called ancestry information makers (AIMs).

For the study, genetic ancestry was based on a panel of 100 AIMs to estimate genetic background.

“Using these genetic markers gives you additional statistical power. It’s no longer two just categories – Black or White; it becomes a continuous variable. Race is not equal to genetics. Genetic markers don’t define specific races,” says Dr. Worsham.

Ultimately, the study found no correlation between West African genetic ancestry and HNSCC outcomes. Only self-reported race was associated with head and neck cancer stage.

Only 5 percent of self-reported African Americans had more than 95 percent West African ancestry, with 27 percent having less than 60 percent West African ancestry. By comparison, 48 percent who self-reported as Caucasian had more than 95 percent European American ancestry.

I’m not too worried about the number of markers. 100 should be sufficient on the scale of continents if well selected. But I’m curious about the representativeness of the sample. The African American one seems more European than others I’ve seen previously. And I really haven’t seen that much admixture with non-Europeans in the CEPH Utah white sample in the HapMap. But perhaps the Utah whites aren’t representative? Dienekes ran ADMIXTURE on the HapMap3 populations a few weeks ago, and I don’t see any elevated component of non-European ancestry in the Utah whites when compared to the Tuscans from Italy.

admixhapmap3

A factoid such as that less than 50% of white Americans are 95% or more European in ancestry can get traction quickly. But I think we should wait a bit and just get more samples. The results are from a presentation at a conference, not even a paper. Of course there’s a possibility that many people have more interesting backgrounds than multi-generational families which settled in Utah rather early. Time will tell.

Addendum: I believe that Native American admixture is going to be more common among the white Americans of the South than Yankees from New England. The reason I would give is that powerful and populous tribes and confederacies such as the Creek and Cherokee persisted in the Southern highlands far longer than in New England. The CEPH sample is going to be biased toward Yankees, as well as European converts from the British Isles and Scandinavia, so perhaps giving a somewhat lower result for non-European ancestry in American whites.

Addendum II: I thought about it more. Something went wrong in their analysis, or they had a very unrepresentative sample. Perhaps they had many Latinos and only coded their self-identified race and not ethnicity (50% of American Latinos identify as white). Maybe the AIMs aren’t good. I don’t know. But I do know that American genealogy buffs who assume Native American ancestry are often very disappointed. They seem to far outnumber those who find surprising non-white ancestry.

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