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  • Medical Genomics

    Posted by Assistant Village Idiot on July 23rd, 2020 (All posts by )

    This is an area where white privilege is real. We are increasingly able to determine risk scores for conditions that might develop later in life, and the large majority of the research subjects have been of North European ancestry. The studies have been done by Americans, Scandinavians, Dutch, etc, and a very large UK Biobank, but consider the motivations of all. Pharmaceutical and other companies have some interest in pure or general research, but mostly they want to be able to develop products for people who might buy them. Where do university labs get their subjects? Governments want to help their own people. 80% of sampling worldwide is Northern European.

    To understand why this matters, we usually take height as an example of a polygenic trait. There have been many SNP’s (smallest units) found to be “associated with” height. Even though they only have enough to account for 15% of the variance at this point, it was enough to predict that Shawn Bradley would be well above-average in height from his DNA alone. (Former NBA. 7’6″) But all of these discoveries are from Northern European samples. When you run the same tests on people of African descent, they show very few of those SNPs associated with height. They have so few, in fact that the test will predict that they are very short indeed, less than five feet, even if they are seven feet tall. Africans have different genes making them taller. A word on the side about these many genes that contribute to height. They are not so much of the form “make the shinbone a little longer,” as more general health items such as digestion and energy conversion, or when hormones activate and when they stop. A fair number may be primarily prenatal influence.

    A further word about “associated with.” Genes often come in long strings on the chromosome from one generation to the next, breaking up only gradually over the centuries, so that we even use this rate of breaking up as a measure of how long ago it was inherited. Therefore, everything on that particular chain will be “associated with” height even if only a couple of them actually have anything to do with height. An example I have heard twice and therefore figure must be common, are the genes “associated with” being able to manipulate chopsticks. Clearly, anything more common in East Asian genes is going to be a positive hit for that association, even though almost none of those genes have anything to do with the skill. This is true for many kinds of research, which is why we say “correlation is not causation.” Social scientists, particularly in education still seem unable to grasp this in practice, however well they can recite it in theory.

    The practical effect is that sometimes preventive interventions target a particular mechanism, so that a medication might be protective. Yet if that medication doesn’t work on you, you are just taking it uselessly – with whatever side effects it produces. Simple accurate prediction is also useful. If you learn your child has a high polygenic risk score for schizophrenia, you put double and triple effort into making sure she doesn’t touch marijuana until she’s thirty-five (probably twenty-five for males). Chinese-Americans may end up doing well despite their low numbers here, because the Chinese are going to be doing that work on their own. But it’s going to be a long slog in Africa. Not only are there not a high percentage of customers there (they will likely have to depend on what we learn from African-American samples), but the genetic variance is so great there that the sampling has to be ten or a hundred times as great. The difference between Khoi-San and Igbo, or the Kikuyu and Tswana are more than four times the genetic distance between me and Australian aborigines, and there’s dozens of those tribes, whose responses to medication are going to vary widely. Stray fact: Africa is large, but dividing it into five easy categories is fairly useful in terms of history. East Africa is very different from West Africa. North Africa is very different from southern Africa, and central Africa is distinct as well. It’s a shorthand starting point to prevent overgeneralization.

     

    5 Responses to “Medical Genomics”

    1. pouncer Says:

      Plurally anecdotal observations —

      My family shops “Asian” grocery stores / markets in North Dallas and suburbs. It is frequent to see Asian (Korean, I think) mother-daughter pairs with a mom not quite five feet tall — and shaped a bit “stumpy” — accompanied by a daughter in her low-teenaged-years, shaped “stalky” with no adolescent curves yet, rocketing along a growth path approaching not quite SIX feet. Presumably the influences are dietary and maybe social, not genetic.

      I attribute it to Texas beef.

    2. Assistant Village Idiot Says:

      The genetic underlies. This is mostly based on prenatal and early childhood nutrition. the Dutch were short, then grew to the tallest in Europe in about a generation. But given the nutrition evening out, there is no further change in Europe. It is easier to break things than to build them.

    3. Robert Prost Says:

      You may remember the holy grail of science in the 1990s – sequencing the human genome. It was prophesied that once complete, disease would be quickly vanished. Counter examples soon emerged. In my institution, we had a researcher who discovered the gene responsible for obesity. A huge amount of money was spent to develop a colony of genetically identical mice. Well, not all the genetically fat mice turned fat and not all the genetically skinny mice stayed skinny. Hmmm. Now epigenetics is a hot area of research because it’s not just DNA, but how the DNA is translated into proteins.

    4. Sgt. Mom Says:

      I had read in a number of sources that post WWII, Japanese schools had to get new and bigger desks after the 1950s or so, since the better and protein-richer diet available let the post-war kids max out their genetic potential for height, after decades of a diet of skimpy rice and veggies.

    5. fiona Says:

      Check out the book Who we Are and How We Got Here. The author investigates ancient DNA now, but he started out doing medical analysis on specific medical issues. The one he singles out is the greater incidence of prostate cancer in African American males. Over time the group traced it to certain genes of greater incidence in West Africans, the group most American Slaves came from. Did they get hurrahs from the liberal establishment? No, they (like the pharmaceutical firms testing African American specific drug reactions) got nothing but accusations of racism and How dare you! I don’t understand this reaction, but it seems to be quite common. Is it related to the different universes we seem to inhabit?