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” when they filled out paper work for the hospital).
But at least the issues with an “Asian” category are clear. Consider the “Hispanic/Latino” category. In the the USA this term also became popular through government fiat around 1970, as a catchall for people whose ancestry derives from the Spanish speaking Americas, with Spaniards, Portuguese, and Brazilians, being border-line cases. Additionally, it has become relatively common in the general American culture to code Hispanic as non-white. This despite the fact that all Latin American populations have large self-identified white populations, with some, such as Argentina and Uruguay, being overwhelmingly white. In the USA between 54% and 92% of Hispanics identify as white in terms of their race. The discrepancy is that some surveys allow for the “Some other race” option, which is the second most popular choice. Surveys which force respondents into a few categories such as white, black, Native American or Asian, produce a result where Hispanics default to a white self-identification.
Implicitly we know it’s more complicated than this mishmash of bureaucratic convenience and opportunistic American identity politics. The HapMap has a Mexican American sample from Los Angeles. Above you see K = 3 in ADMIXTURE for Mexican Americans. Each thin “slice” is an individual, with the color proportions reflective of genomic contributions of one of three putative ancestral groups.The full plot had Europeans and Chinese as well. Blue seems to correspond with Native American, and red white European (the green residual is modal in East Asians). Los Angeles’ Mexican American community is obviously mixed-race. What in Latin American might be termed mestizo. And yet according to the survey data when forced to choose this community seems to affiliate with a white Spanish identity, blanco. Seeing as almost all of them are Spanish speaking and not indigenous (I am aware that the USA has a small and growing non-Spanish speaking Latino population of indigenous immigrants), this would make sense. But another facet of Mexican American identity surfaces in the concept of Aztlán, which is a nod to the Nahua roots of much of the Mexican population.
But whatever the the cultural nuance and subtly, which can be decomposed at length, it is also important to properly characterize the genetic structure of the Hispanic populations. Some Mexican Americans are predominantly white European in ancestry, and some are predominantly Amerindian. Many are mixed in roughly equal proportions. This is not just a minor detail. Going back to my first paragraph, a new letter to Nature Genetics reports on the differential response to treatment in children with leukemia proportional to Native American ancestry. Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia:
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.
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…
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.
In 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: