* This domain has almost all the archives on gnxp.com, including many comments, going back to 2002

* My specific content from this weblog, ScienceBlogs, and Discover, can be found at Unz Review, where I’m posting. ]]> http://www.gnxp.com/new/2014/03/30/gnxp-status-update/feed/ 0 http://www.gnxp.com/new/2012/06/04/10-years-of-gene-expression/ http://www.gnxp.com/new/2012/06/04/10-years-of-gene-expression/#comments Mon, 04 Jun 2012 07:54:57 +0000 http://www.gnxp.com/wp/?p=1491 Just thought I would mention that a few days ago the weblog Gene Expression has been around for 10 years. I won’t say much more at this point because of time constraints. But I wanted to enter it into the record, as well as admitting two minor points. I often used to say in the early days that my foray into blogging was rather a coincidence. I was playing around with the JSP/Servlet platform and wrote up a primitive blog software which I decided to test with my own weblog…and somehow one thing led to another. But I’m 99% sure now that at some point I would have started a weblog, and soon in relation to 2002. Second, of late I notice that Gawker is occasionally mentioned in the media as the locus for various politically correct outrages. If you had asked me 10 years ago that Gawker would be such a banal and conventional website I would have been surprised. The founding editor of Gawker was an occasional contributor to the first incarnation of GNXP in 2002. People tend to idealize the early blogosphere too much, there was a lot of stupid Iraq warblogging going on (I was part of it to some extent), but there definitely was some amalgamation of heterodoxy. Today the blogosphere reflects the mainstream media by and large.

On the other hand, the F2 generation might be potentially very light indeed (or dark)….

My friend Steve Hsu gave a talk at Google today. Here are the details:

I’ll be giving a talk at Google tomorrow (Thursday August 18) at 5 pm. The slides are here. The video will probably be available on Google’s TechTalk channel on YouTube.

The Cognitive Genomics Lab at BGI is using this talk to kick off the drive for US participants in our intelligence GWAS. More information at www.cog-genomics.org, including automatic qualifying standards for the study, which are set just above +3 SD. Participants will receive free genotyping and help with interpreting the results. (The functional part of the site should be live after August 18.)

Title: Genetics and Intelligence

Abstract: How do genes affect cognitive ability? I begin with a brief review of psychometric measurements of intelligence, introducing the idea of a “general factor” or IQ score. The main results concern the stability, validity (predictive power), and heritability of adult IQ. Next, I discuss ongoing Genome Wide Association Studies which investigate the genetic basis of intelligence. Due mainly to the rapidly decreasing cost of sequencing, it is likely that within the next 5-10 years we will identify genes which account for a significant fraction of total IQ variation.

We are currently seeking volunteers for a study of high cognitive ability. Participants will receive free genotyping.

From what I recall of my discussion with Steve the aim here is to fish in the extreme tail of the distribution to see if that allows for an easier catchment of I.Q. upward incrementing alleles. 3 standard deviations above the mean I.Q. is about 1 out of 750 individuals or so.

The recent announcement of a new journal sponsored by the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust generated a bit of discussion about the issues in the scientific publishing process it is designed to address—arbitrary editorial decisions, slow and unhelpful peer review, and so on. Left unanswered, however, is a more fundamental question: why do we publish scientific articles in peer-reviewed journals to begin with? What value does the existence of these journals add? In this post, I will argue that cutting journals out of scientific publishing to a large extent would be unconditionally a good thing, and that the only thing keeping this from happening is the absence of a “killer app”.

It works for physics, computer science, and to a great extent the social sciences. Why not the biosciences?

End Update

Over the past few days I’ve been very disturbed…and angry. The reason is that I’ve been reading Misha Angrist and Dr. Daniel MacArthur. First, watch this video:

In the very near future you may be forced to go through a “professional” to get access to your genetic information. Professionals who will be well paid to “interpret” a complex morass of statistical data which they barely comprehend. Let’s be real here: someone who regularly reads this blog (or Dr. Daniel MacArthur or Misha’s blog) knows much more about genomics than 99% of medical doctors. And yet someone reading this blog does not have the guild certification in the eyes of the government to “appropriately” understand their own genetic information. Someone reading this blog will have to pay, either out of pocket, or through insurance, someone else for access to their own information. Let me repeat: the government and professional guilds which exist to defend the financial interests of their members are proposing that they arbitrate what you can know about your genome. A friend with a background in genomics emailed me today: “If they succeed in ramming this through, then you will not be able to access your own damn genome without a doctor standing over your shoulder.” That is my fear. Is it your fear? Do you care?

In the medium term this is all irrelevant. Sequencing will be so cheap that it will be impossible for the government and well-connected self-interested parties to prevent you from gaining access to your own genetic information. Until then, they will slow progress and the potential utility of this business. Additionally, this sector will flee the United States and go offshore, where regulatory regimes are not so strict. BGI should give glowing letters of thanks to Jeffrey Shuren and the A.M.A.! This is a power play where big organizations, the government, corporations, and professional guilds, are attempting to squelch the freedom of the consumer to further their own interests, and also strangle a nascent economic sector of start-ups as a side effect.

You are so much more than your genes. So much more than that 3 billion base pairs. But they are a start, a beginning, and how dare the government question your right to know the basic genetic building blocks of who you are. This is the same government which attempted to construct a database of genetic information on foreign leaders. We know very well then who they think should have access to this data. The Very Serious People with a great deal of Power. People with “clearance,” and “expertise,” have a right to know more about about your own DNA sequence than you do.

What can you do? What can we do? Can we affect change? I don’t know, I can’t predict the future. But this is what I’m going to do.

1) I am going to release my own 23andMe sequence into the public domain soon. I encourage everyone to download it. I would rather have someone off the street know my own genetic information than be made invisible by the government. That is my right. For now that right is not barred by law. I will exercise it.

2) Spread word of this video via social networking websites and twitter. The media needs to get the word out, but they only will if they know you care. Do you care? I hope you do. This is a power grab, this is not about safety or ethics. If it was, I assume that the “interpretative services” would be provided for free. I doubt they will be.

3) Contact your local representative in congress. I’ve never done this myself, but am going to draft a quick note. They need to be aware that people care, that this isn’t just a minor regulatory issue.

4) The online community needs to get organized. We’re not as powerful as a million doctors and a Leviathan government, but we have right on our side. They’re trying to take from us what is ours.

5) Plan B’s. We need to prepare for the worst. Which nations have the least onerous regulatory regimes? Is genomic tourism going to be necessary? How about DIYgenomics? The cost of the technology to genotype and sequence is going to crash. I know that the Los Angeles DIYbio group has a cheap cast-off sequencer. For those who can’t afford to go abroad soon we’ll be able to get access to our information in our homes. Let’s prepare for that day.

This is a call to arms, a start. I’ve been complacent about this issue, focusing more on the fascinating aspects of ancestry inference which are enabled by personal genomics. No more. I’ll be doing a lot of reading today. If you have a blog, post the video. Raise awareness. Let’s make our voices heard. If they take away our rights because we’re silent, we have only ourselves to blame. If they take aware our rights despite our efforts, we’ll set up the infrastructure for the day when we can take back what is ours.

P.S. Feel free to post info and ideas in the comments. I just literally woke up to the urgency of this issue in the past 48 hours.

Finally, I know 3-D visualization is bad form, but I went for it anyway. Below is a cube which shows the positions of Gujaratis, Chinese, Mexican Americans, and Utah whites and Tuscans from the HapMap, along with a few extra samples from friends and family. Can you tell where my parents are?

This is what Dienekes also found. Aggregating various ancestral components together to be analogous to what Zack produced at K = 5, you get the bar plot below from his runs:

I assume that all ancestry analyses will find that I have a substantial minority of East Eurasian ancestry. I have a similar amount of ancestry which is obviously connected to West Eurasia. And the rest of my ancestry is going to fall into the catchall which is “South Asian,” which Reich et al. in Reconstructing Indian History argued was in fact a compound between a West Eurasian-like population (“Ancestral North Indian,” ANI) and a South Eurasian population (“Ancestral South Indian,” ASI) which was more closely related to East Eurasians than West Eurasians, though distantly so at that (modern West Eurasians are interchangeable with ANI, but ASI do not exist in unadmixed form).

Finally, here’s an analysis of chromosome 1 and its affinities to various reference populations. I’ve labelled myself. No surprises:

I am HRP002 in HAP. DOD075 in Dodecad. IN8 in BGA. I am willing to submit to any of these new grassroots ancestry projects if they want me. But I doubt I’ll find anything too surprising now. They converge upon the same rough proportions (as they should).

I’m at the stage where I want to look more deeply into the details of how long ago the “eastern” admixture occurred. It seems to come down from both parents. If it was very recent there should be some linkage disequilibrium detectable because recombination should not have broken down the allelic associations distinctive to each ethnic group yet (this is noticeable in African Americans). But I am not so sure it is recent anymore, as I’d thought. I suspect a Tibeto-Burman and Munda element were absorbed by Bengali peasants in the course of demographic expansion in what became Bangladesh between 1000 and 1500 A.D., and that ancestry is well distributed across the population now.

But even though I won’t find anything out for myself, the reason HAP and projects like it are useful is that we need better coverage of the world’s variation. There are big coarse questions which we’ve tapped out, but there are still lots of gaps to fill. I’m willing to do my part in that (or, more precisely, at this point I’ve drafted my parents into the role, since they aren’t related and so represent two independent data points for Bengal).

Addendum: I know for many people of European ancestry this sort of thing doesn’t tell them anything new. Not so for me. I always suspected East Asian admixture due to the phenotype of my extended family (and to some extent, me. I did not need to shave regularly until my 20s), but I was always curious as to its extent. Additionally, for the reasons of phenotype I had assumed my mother had very little of such ancestry while my father had a great deal. It turns out that in fact my mother may marginally be more “eastern” than my father.

- Albion’s Seed. I read this in 2004, and it was a page turner.

- The Cousins’ Wars. I had thought of Kevin Phillips as a political writer, but this was a very engaging and deep cultural history. My prejudice resulted in my not reading this until 2009.

- What Hath God Wrought. This book focuses on the resistance of the Whigs and Greater New England to the cultural ascendancy of the Democrats and their “big-tent” coalition which included most of the South, the Mid-Atlantic, and much of the “Lower North” (e.g., the “butternut” regions of the Midwest settled from the Border South).

- The Rise of American Democracy. This is a good compliment to the previous book, in that it takes the “other side,” that of the Democrats. In many ways this is the heir to Arthur Schlesinger’s Age of Jackson.

- Throes of Democracy. A somewhat “chattier” book than the previous ones, it is still an informative read. It covers a period of history with the Civil War as its hinge, and so gives one the tail end of the Age of Sectionalism.

- Freedom Just Around the Corner. By the same author, but covering a period of history overlapping more with Albion’s Seed.

- The Age of Lincoln. This is not a “Civil War book.” It is of broader scope, though since the the war is right in the middle of the period which the book covers it gets some treatment. I’d judge this the “easiest” read so far of the list.

- Replenishing the Earth. This is about the Anglo world more generally, but it is nice to plug in America into a more general framework. North America is not sui generis.

- The English Civil War. This is obviously not focused on America, but it is a nice complement to Albion’s Seed, as it shows the very deep roots of the division between two of America’s folkways. The Cousins’ Wars serves as a bridge between the two, shifting as it does between both shores of the Atlantic.

I’m game for recommendations! I had a relatively traditional education in American history, and did very well in my advanced courses, but I knew very little before I read books like this.

1936 presidential election, blue = F.D.R.

Walter Russell Mead has a fascinating blog post up, The Birth of the Blues. In it, he traces the roots of modern American “Blue-state” liberalism back to the Puritans, the Yankees of New England. This is a plausible argument. I believe that many social-political coalitions and configurations in contemporary America do have deep historical roots. But assertions and models must be tested. It is for example absolutely correct that early New England was the redoubt of American statism. First the Federalists, and then later to a lesser extent the Whigs, took refuge in New England during the long phase of anti-government Democratic ascendancy which led up to the presidency of Abraham Lincoln. But New England statism has its limits; the map above shows that it is in Greater New England that resistence to FDR seems to have been deepest. I don’t necessarily chalk this up to “flinty Yankee” anti-government sentiment. Rather, I think we need to consider that the ideological content of social-political coalitions and configurations sometimes matter less than long persistent affinities across cultural networks and domains.

Very few Americans for example are aware today that in 1800 New England was the region with the strongest adherence in the United States to orthodox Protestant Christianity. In contrast, Deism was firmly rooted among the Southern planter aristocracy. As late as 1850, even after the Second Great Awakening transformed the religious landscape of the South, the conservative Carolina aristocrat John C. Calhoun remained a Unitarian. And it was in the South than support for Revolutionary France ran strongest, while New England favored the United Kingdom and its allies. I suspect most modern Americans would be taken aback by such affinities simply based on the substance of what New England and the American South represent in terms of ideology at any given moment.

Until a few years ago I was very ignorant of American history. And therefore I was totally innocent of many important patterns which span the generations in our nation. Scholars such as Walter Russell Mead would have impressed me with their erudition, but I didn’t have the data base to evaluate the plausibility of their claims. In everyday discourse we often bandy about history learned when we were teenagers as if they can serve as robust frames for the sorts of inferences we make. Alas, they can not. There is no substitute for genuine knowledge. Albion’s Seed is a good start, but many accessible books which cover the first period of American sectionalism are filled with much relevant insight.

So where does this leave this website? The archives are obviously active and useful for many people. Even without any front page content this blog serves 1-2,000 pages per day just as a function of search engines sending traffic to old posts. That’s important. GNXP could turn into an archive site, as I always imagined it would at some point, and still play a vital role in the information ecology.

But I’m not ready to turn this into a hibernating site yet. Kevin and David are still posting obviously. And, because of the traffic and the old links that come to this domain GNXP has good PageRank. My main interest then is to promote science bloggers whose content should “get out there.” So I’ve been soliciting contributions from people now and then with the promise that cross-posting will boost the PageRank of their site and give them some publicity. If you have a weblog with content that I think would fit the front page of this weblog, and are interested in cross-posting, feel free to email me at contactgnxp -at- gmail.com with a link. I’ll add it to my RSS and see if it’s a good fit. If you seem a good candidate for front page privs, I’ll shoot you an email with the details about your login, etc.

Additionally, I’ve modified the column format some. At the top of the sidebar now are a set of articles which come from an aggregation site where I curated various weblog RSS feeds (as well as some google searches). And, there’s always my pinboard and Jason’s delicious. There’s also a footer column now where you can find archives, books, etc.

I’ll probably be tweaking with the format and what not every now and then. All things must change.

Speaking of using PageRank, the Harappa Ancestry Project now has its own domain, http://www.harappadna.org. If you’re South Asian, Iranian, Tibetan, or Burmese, please check it out.

http://www.zackvision.com/weblog/2011/01/harappa-ancestry-project

This is the feed:

http://www.zackvision.com/feed/

If your ancestry is from these nations:

• Afghanistan
• Bangladesh
• Bhutan
• Burma
• India
• Iran
• Maldives
• Nepal
• Pakistan
• Sri Lanka
• Tibet

Read on! If not, “for entertainment purposes only”….

I have been griping in public and in private about the “reference” populations used for South Asian genomics for years. Because of the Permit Raj the HGDP had to use Pakistani populations. Additionally, because of the HGDP’s mandate to focus on smaller groups which might harbor genetic uniqueness you have some very obscure tribes, but only one sample set from an Indo-Aryan speaking population. And even there, it was a minority, not the Punjabi speaking majority of Pakistan.

Some of this has changed in recent years. Papers such as Reconstructing Indian History and Genetic diversity in India and the inference of Eurasian population expansion have added more populations to the mix. The current phase of the HapMap has Gujaratis from Houston. But there is always a problem when you take a small population set to be representative of a broader group. There are ~1.3 billion South Asians. Using Gujaratis from Houston, who are likely to be of a narrow range of castes, is still problematic. Because of the long history of endogamy and likelihood of fine-grained caste and geographical structure good population coverage is of the essence for South Asians. Taking the Beijing HapMap sample as representative of Han Chinese is not optimal, but this sort of thing would be far less optimal in South Asia.

So when Dienekes began the Dodecad Ancestry Project I was very curious. I had had ADMIXTURE for a while, but it prompted me to start playing around with it myself. My plan was to wait to see how Dienekes fared. In particular, what didn’t pan out in terms of fruitful use of labor. Mine is finite, like everyone’s. My medium term plan was to start up a South Asian equivalent to Dodecad at some point in the first half of 2011.

Then Zack approached me. I know Zack from the internet since 2003 through the blogs. His primary interest in blogging was about Pakistani culture and liberal politics (he’s Pakistani American and a liberal). But he also has a doctorate in electrical engineering, so he has some technical skillz. It turns out that because of Zack’s own peculiar genetic background (he’s 1/4 Egyptian) he kept asking me questions. Eventually it became clear that he was interested about starting something similar to Dodecad…and I told him my own future plans, and encouraged him to take up the torch immediately. I knew Zack had the technical chops, and also could probably devote more time and energy at the time than I could.

I immediately gave him my 23andMe sample. Since I had Dienekes already run my genome we kind of knew what to expect. And it looks like Zack has the software running well. He included a Nepali sample, and it turns out that in an MDS clustering I fell 71% into the dominant Nepali cluster. This is kind of what I expected.

In any case, the details:

Please do not send samples from close relatives. I define close relatives as 2nd cousins or closer. If you have data from yourself and your parents, it might be better to send the samples from your parents (assuming they are not related to each other) and not send your own sample.

If you are unsure if you are eligible to participate, please send me an email (harappa@zackvision.com) to inquire about it before sending off your raw data.

What to send?
Please send your All DNA raw data text file (zipped is better) downloaded from 23andme to harappa@zackvision.com along with ancestral background information about you and all four of your grandparents. Background information would include where they were born, mother tongue, caste/community to which they belonged, etc. Please provide as much ancestry information as possible and try to be specific. Do especially include information about any ancestry from outside South Asia.

Data Privacy
The raw genetic data and ancestry information that you send me will not be shared with anyone.

Your data will be used only for ancestry analysis. No analysis of physical or health/medical traits will be performed.

The individual ancestry analysis published on this blog will be done using an ID of the form HRPnnnn known to only you and me.

What do you get?
All results of ancestry analysis (individual and group) will be posted on this blog under the Harappa Ancestry Project category. This will include admixture analysis as well as clustering into population groups etc.

I suggest you read about Dienekes’ analysis on South Asians for an idea about what to expect.

You can access all blog posts related to this project from the Harappa Ancestry Project link on the navigation menu on every page of my website. You can also subscribe to the project feed.

If you’re South Asian, Iranian, Burmese, or Tibetan, and have a 23andMe genotyping done, you know what to do. If you know someone from these groups who have had that done, please forward this one.

Or to put it another way, Christians need to find a way to thrive in a society that looks less and less like any sort of Christendom — and more and more like the diverse and complicated Roman Empire where their religion had its beginning, 2,000 years ago this week.

A little over five years ago I wrote, A prayer for the Emperor. I concluded:

Because of their diversity, ultimately I suspect the religious orders and groups have to be either subordinate or oppositional to the state. This was the trend in ancient Rome or China. In contrast, Westerners have had a model where one a powerful exclusive religious institution strikes hard bargains with states as if they were equals (the Roman Catholic Church). Or, in nations like Norway, the national church has been absorbed by the state so the two are coterminus. The diffusion of religious power to innumerable bodies will inevitably result in the pulling back of the strong reverential stance that American politicians right now seem to take to all religions, so long as they aren’t so deviant as to practice animal sacrifice. At least that’s what I’d bet on.

Douthat responded:

I agree with some of this, but I’m skeptical about the last part. The dogma-free, “operational ecumenicism” that he describes hasn’t made politicians less reverential toward religion so far - if anything, the decline of the old dogmatic boundaries separating Protestant churches from one another, and Protestants from Catholics, has had the opposite effect. The less that believers care about their doctrinal differences, the more they can band together for more general political purposes – stopping gay marriage, for instance – and the more it makes sense for politicians to address their concerns. Whereas once a politician couldn’t make specific appeals to Catholics without offending Baptists, and vice versa, today he doesn’t have to worry about those kind of differences, and can just focus on the political issues that unite megachurch worshipers with Catholic home-schoolers, Orthodox Jews, and so on.

I think Douthat’s critique of my prediction has been born out, insofar as Barack H. Obama did utilize a watered down form of god-talk in 2008, despite his likely personal skepticism of the supernatural claims of religion. What I think both Douthat and I missed at the time was what he alludes to in his current column: the swelling tide of secularism which arose as a reflex to conservative religious activism. That being said, I think in many ways the analogy to ancient Rome does hold, even if my specific inferences were incorrect. A minimal threshold of public piety, no matter personal belief, is demanded of politicians today. No sect commands dominance in the public arena, and a syncretic ecumenical ceremonial deism reigns supreme, though both the New Atheists and religious traditionalists object to its ascendancy.

This is naturally not a endorsement of every claim made in this book. But whatever the substantive facts, the author managed to implement the plan of argument and the marshaling of evidence in a fashion which is extremely impressive.

(Acknowledgement, John Hawks)