About two and a half months ago I brought your attention to the fact that there is population substructure in the Gujaratis of Houston. That might sound strange, but here’s the back story. Over the past ~10 years or so there has been a project attempting to catalog common human genetic variation, known as the HapMap. The HapMap began with East Asian, West African, and European groups. But over the years it has been expanding. The first South Asian population added to the database were people of Gujarati origin in Houston, Texas. Therefore, you had a situation where in the medical genetic literature there was a lot of talk about “Gujaratis from Houston,” as if that was a group of particular importance.

The ultimate pragmatic rationale for the catalog was to allow researchers to control for ancestry when attempting to fix upon genes implicated in disease. By illustration, if Chinese have disease X at a greater frequency than Europeans, if you had a common pool of Chinese + Europeans then all the genetic variants associated with the Chinese might come up as causal, when actually it’s just a correlation with ancestry. Continue reading →

The question of national and individual origins has a corporeal and concrete dimension, and a mythic and symbolic one. This is evident in the religious traditions which most of the world’s populations adhere to. Israel is both literally and figuratively a descent group. They issue from the tribes descended from the sons of Jacob. Those who convert into the Jewish religion customarily also convert into the Jewish nation, and so figuratively share the same descent. Similarly, among Muslims there is a particular prestige given over to the descendants of Muhammad, the Sayyids. Within Hinduism the importance of descent groups manifests generally in terms of the endogamy prevalent among South Asians, and also in specific cases, such as with gotras. The fundamental atomic basis of Confucian religious morality is arguably filial piety. Confucius’ descendants still play a prominent role in modern China promoting his ideas.

But descent also has a scientific and concrete aspect. Sometimes the mythic and scientific align. It does seem that the notional male line descendants of Genghis Khan are actually descended from one individual who flourished ~1,000 years ago. In other instances the connection is complex. Jews do seem to share common descent, but it is also evident that they have mixed greatly amongst the nations. And sometimes the inferences generated by science may warrant a reconsideration of treasured myths. Most reasonable people will probably accede to the clear overwhelming descent of South Asian Muslims from the native people of the Indian subcontinent, but the genetics clinches that. True, there is quite often a clear trace of Middle Eastern and African ancestry among the Muslims of South Asia above and beyond what may be found amongst non-Muslims, but often this component is dwarfed by a minor East Asian element which seems to warrant no cultural memory! Continue reading →

I know that many people took advantage of the 23andMe sale I highlighted on Sunday. I also know that a fair number of these were brown, as I also have a list of people who I emailed, and several South Asians confirmed that they’d purchased the 23andMe kit. What do you get if you purchase this kit? Basically 1 million markers, SNPs, which are simply population-wide variant positions within your genome. These markers were chosen because variation is often informative, in terms of traits, as well as ancestry.

But obviously you are not going to just be looking at a string of letters. The data has to be analyzed for you. 23andMe provides a range of tools in this domain. But, one needs to use them cautiously, and also understand their limitations. In particular, these tools were often tuned for a specific set of populations which does not include South Asians. So some of the results are going to strike you as strange.

First, let’s hit the easy stuff. Health and traits. Continue reading →

About a month ago I put up my first post on this weblog. I argued that South Asians have been genetically undersampled, which is rather alarming considering that Indians, Pakistanis, Bangladeshis, Nepalis, Sri Lankans, etc., are 1/6th of humanity. The alarming part is that understanding population genetic structure is considered a prior condition of much medical genetic research. Without taking into account genetic relatedness one can not usefully establish correlations between particular variants and particular diseases or traits. For example, it is well known that South Asians have a high risk for diabetes, but the possible risk variation within this genetically diverse group has barely been addressed (there is some data which indicate that Bengalis and South Indians are at more risk than Punjabis). Continue reading →

The 2009 paper Reconstructing Indian population history was a watershed in understanding the genomics of South Asians. Before this point the studies had been with unrepresentative samples, fewer markers, or, South Asians were only a sidelight. This paper put the focus on South Asians to elucidate the group’s population history (it still undersampled eastern South Asians, though this seems part of the plan because of their focus on two, not three, ancestral Indian components). If you want to know more about the paper, here is the ungated version. But in this post I want focus on an issue which you can find only in the supplements to the paper.

The HapMap project, which surveys genetic variation in world populations, has a set of Gujaratis, from Houston, Texas. This is currently the primary population of Indian origin you have to work with in the public data sets. There are other South Asian populations in the public domain, but their number of markers is far lower. So the Gujarati sample is very useful right now. But one thing that immediately jumps out at you is that there are in fact two Gujarati clusters. In the PCA plot I’ve extracted from the supplements you see the two largest components of genetic variation. PC 1, the x axis, separates whites from South Asians, and PC 2, separates one group of Gujaratis from everyone else. What’s going on here?

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Two issues compel this post. One is practical. The other is more, shall I say, spiritual (or at least fun!). In regards to the first, a few weeks ago I reviewed a paper which reported that the efficacy of response to a particular leukemia treatment regime was dependent on the amount of Native American ancestry an individual had. One has to be specific here, because many people who are white or black American have significant Native American ancestry (Brett Favre’s paternal grandfather was Choctaw), and many people who identify as Native American may not have as much Native American ancestry as others. But for the purposes of this blog post, I want to bring to your attention the figure above, which I extracted from the paper. Its implications may pose a major problem in the future for South Asian biomedical research in the United States. Continue reading →

Wired has a totally charming story of one man’s quest to understand and beat the confounding scratch-off lottery ticket:

Mohan Srivastava, a geological statistician living in Toronto, was working in his office in June 2003, waiting for some files to download onto his computer, when he discovered a couple of old lottery tickets buried under some paper on his desk. The tickets were cheap scratchers–a gag gift from his squash partner–and Srivastava found himself wondering if any of them were winners. He fished a coin out of a drawer and began scratching off the latex coating. “The first was a loser, and I felt pretty smug,” Srivastava says. “I thought, ‘This is exactly why I never play these dumb games.'”

The second ticket was a tic-tac-toe game. Its design was straightforward: On the right were eight tic-tac-toe boards, dense with different numbers. On the left was a box headlined “Your Numbers,” covered with a scratchable latex coating. The goal was to scrape off the latex and compare the numbers under it to the digits on the boards. If three of “Your Numbers” appeared on a board in a straight line, you’d won. Srivastava matched up each of his numbers with the digits on the boards, and much to his surprise, the ticket had a tic-tac-toe. Srivastava had won $3. “This is the smallest amount you can win, but I can’t tell you how excited it made me,” he says. “I felt like the king of the world.”

Delighted, he decided to take a lunchtime walk to the gas station to cash in his ticket. “On my way, I start looking at the tic-tac-toe game, and I begin to wonder how they make these things,” Srivastava says. “The tickets are clearly mass-produced, which means there must be some computer program that lays down the numbers. Of course, it would be really nice if the computer could just spit out random digits. But that’s not possible, since the lottery corporation needs to control the number of winning tickets. The game can’t be truly random. Instead, it has to generate the illusion of randomness while actually being carefully determined…”

Srivastava had been hooked by a different sort of lure–that spooky voice, whispering to him about a flaw in the game. At first, he tried to brush it aside. “Like everyone else, I assumed that the lottery was unbreakable,” he says. “There’s no way there could be a flaw, and there’s no way I just happened to discover the flaw on my walk home.”And yet, his inner voice refused to pipe down. “I remember telling myself that the Ontario Lottery is a multibillion-dollar-a- year business,” he says. “They must know what they’re doing, right?” [Link]

This story reiterated in my mind how important it is to have a good understanding of science and mathematics in modern society. Consider how many activities in your day are governed by a mathematical code or logical pattern of some kind. Every minute you spend on Facebook you are helping Facebook perfect and equation to predict what you might buy for example. Nerds are poised to inherit the future.

Continue reading →