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selec By now you have read about the new paper in Science, Greenlandic Inuit show genetic signatures of diet and climate adaptation. Carl Zimmer has an excellent treatment in The New York Times, Inuit Study Adds Twist to Omega-3 Fatty Acids’ Health Story. The backstory here is that for decades people have been told to take fish oils because of their possible protective role against heart disease. Apparently some of these recommendations were based on observing the dietary habits of indigenous peoples of the Arctic and their health outcomes. Unfortunately studies which attempt to gauge the impact of these recommendations on Western populations have come back mixed at best. I myself stopped taking fish oils years ago after a review of the literature and asking around. Well, it turns out that there may have been a confound that the populations of the Arctic are adapted to their particular diet.

The figure to the right gets at the heart of the result. Greenland Inuit (they selected for individuals with less than 5% European ancestry), Europeans, and Chinese, exhibit a particular genome-wide pattern of relatedness, which you can see at the bottom. Looking at their results the authors found that there is gene flow from a Greenland-like population to the Chinese at some point over the last 20,000 years. This seems plausible. Additionally, I recall that Greenland natives and Europeans share Ancestral North Eurasian heritage. This is not a population genomics paper focused on phylogenomics, so these details aren’t too important. The takeaway is that on a set of derived alleles around the fatty acid desaturase genes the populations of Greenland seem fixed for variants which are very different from the major alleles in both Chinese and Europeans. These genes are very extreme in terms of their results on the population branch statistic (PBS), which measures deviations in allele frequency against reference groups.

The details are somewhat gnarly. The authors look at several groups of genes, before zeroing in on the FADS group, and they also look at several variants within FADS, as well as various phenotypes. It turns out some markers make the Inuit differ in height and weight, and the height result also applies to Europeans (the frequency is far lower, so that may be why it wasn’t picked up in earlier GWAS).

But I want to focus on a major top-line result. First, here is Rasmus Nielsen in Carl’s piece, “The same diet may have different effects on different people.” And from the paper itself: “In addition to the associations with height, we also found known associations with low fasting serum levels of insulin, total cholesterol, and LDL cholesterol for European carriers of low-frequency–derived alleles of FADS1 variation, suggesting that there may be a protective effect of these variants on cardiometabolic phenotypes.” The implications of this study are commonsense, but they’re also very deep, as they confirm a deep intuition that the same dietary regime may not have the same outcome in all humans. As the authors note in the piece many of alleles at high frequency in Greenlanders are also at high frequency in American native populations in general. Looking at the time depth of the selection event it seems likely that a lot of change occurred in Beringia or Siberian, so for New World groups this may be an ancestral suite of characteristics. But perhaps even more interesting is that many populations have high minor allele frequencies of these alleles. I looked at one marker in the 1000 Genomes data set, and the range is wide. Many Eurasian populations have the “Greenland” variant at ~10% frequency, so ~1% might be homozygote for that genotype.

5169qqIjeZL._SX309_BO1,204,203,200_ What that means is that studies in small populations like the natives of Greenland may still have wide-ranging implications. There are literally hundreds of millions of people with these alleles. Though one might suggestion caution about extrapolating results out-of-population, some of the phenotypes are replicated already in Europeans who have the variant.

This study can’t be understood in isolation. It allows for broader generalizations. Ten years ago I read Why Some Like It Hot: Food, Genes, and Cultural Diversity. This was really a pre-genomic era book, drawing on an older body of work. But it is very interesting, and reports on a wide range of studies and the author’s own experiences. Much of it won’t be a surprise to many, but others would still benefit from its comparative method. Today we know a lot more about population-level variation, and what it might tell us about individual-level variation. It’s going to be fun times ahead, as I suspect that the intersection of diet, nutrition, genomics, and quantified-self is going to be a very big deal in the near future.How and what we eat is important. The diet industry is nearly a one hundred billion dollar market.

 
• Category: Science • Tags: Genomics 
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  1. The shoe that I am waiting to see drop is the recommendation of a Mediterranean diet, in which one of the main validating tests was conducted involving Spanish women.

    While the traditional Mediterranean diet has been shown, beyond question, to be beneficial in people with Mediterranean ancestry, it is not at all obvious to me that these benefits are equally great for people whose ancestry is remote from that region of the world (e.g. Scandinavians or Koreans).

    • Replies: @granesperanzablanco
    One significant difference between Med populations and others is the rate of APOe4 carries. It is very low in Southern Europe but higher in Northern Europe. As a heterozygote I am keenly interested in the optimal diet for me.
  2. Yup. Different groups have had to adapt to different diets. So trying to fashion diet advice based on what one group does was bound to be foolhardy (about as useful as the advice “copy the habits of successful people”).

    Readers see also:

    HBD is Life and Death

    Even George W. Bush Has Heart Disease

  3. one thing i want to emphasize: the genetic variants at high frequency in one population may be at low, but non-trivial frequency in others. so re: portability of med. diet. let’s say it is optimzied for people with a mediterranean genotype. if we get most of the major alleles nailed down, then that’s actionable information for non-med people. if, for example, 25% of han chinese would benefit from the med. diet that’s more people than actually consume the mediterranean diet due to their culture.

    p.p.s. more and more convinced that gut flora is also a major variable, and that might be heritable or have co-factors (e.g., perhaps lack of use of some types of antibiotics in some cultures makes some diets more effective?)

  4. The evidence that Eskimos had low rates of heart disease has not held up well:

    Fodor et al, ‘“Fishing” for the Origins of the “Eskimos and Heart Disease” Story: Facts or Wishful Thinking?’
    Canadian Journal of Cardiology (2014)
    http://www.sciencedirect.com/science/article/pii/S0828282X14002372

  5. Would a similar research on Indians vs. Myanmarese/Cambodians/Laotians/Bangladeshis on Carbohydrate consumption ( recommendation of 60% energy from carbs) vs. Type 2 diabetes. The 60% recommendation is made across the board, but it appears the impact is worst on Indians. Elizabeth HoLiday identified some unique SDaiabetes markers in south Indian populations; a number of others have claimed that they have identified unique markets, but no convincing proof exists.

  6. ““The same diet may have different effects on different people.”

    My gut feel is the full consequences of this will be huge.

  7. Fish oil is not the same as eating fish

    Omega 3 supplements + pizza and Coke shouldnt mirror the biomarkers of a traditional diet.

  8. http://www.circumpolarhealthjournal.net/index.php/ijch/article/view/18001

    There is in fact evidence that the Inuit have compensated for decreased production of vitamin D through increased conversion to its most active form and through receptors that bind more effectively.

    http://www.ncbi.nlm.nih.gov/pubmed/12719317

    For Inuit children, a traditional diet contains 20 mg of elemental calcium per day, well below the recommended daily intake. To identify alterations in intestinal or renal calcium absorption, 10 healthy Inuit children (5 to 17 years of age) were given a standardized calcium load (Pak test). Five had hypercalciuria (hyperabsorptive in 3 and renal leak in 2), a frequency markedly different from that for white children (p < 0.004) and not explained by calcitropic hormone and serum calcium levels, which were normal. There was a preponderance of the bb vitamin D receptor genotype (8 of 10 subjects; p < 0.01 for comparison with white populations). Dietary calcium absorption appeared to be more efficient in these Inuit children, with an increased frequency of hypercalciuria associated with the bb genotype. This may represent a genetic adaptation to dietary constraints and may predispose to nephrolithiasis or nephrocalcinosis if standard nutritional guidelines are followed

    https://en.wikipedia.org/wiki/Umami

    Umami (/uːˈmɑːmi/), a savory taste,[1][2][3] is one of the five basic tastes (together with sweetness, sourness, bitterness, and saltiness)

  9. I have 23amdme – is there a simple way for me to figure out if I have the ‘fish oil is good’ variant from their available data? I’m a bit of a noob at this.

    • Replies: @notanon
    I don't know the answer but one day I expect that's exactly the kind of readout you could get with lists of good and bad foods for you personally.
  10. Slightly OT: There was another study on BMI and height in Europe last week – http://medicalxpress.com/news/2015-09-tall-slim-genetic.html, where they apparently found that genes for taller height reduce BMI, and that they would predict the genetically taller European populations to have genetically lower BMI.

    I don’t doubt that genes which increase height, all else equal, decrease BMI . After all, unless those variants actually adding to weight as well, BMI = weight / height. The same muscle and lean mass over a taller frame = lower BMI. So if many genes related to height simply relate to increased and prolonged bone growth without boosting lean mass (which is the majority contributor to BMI for most folk), then they would lower BMI.

    But I wonder if they actually captured the whole signal. Obviously European populations do not actually vary such that the taller populations have lower BMI. Their take is that “environmental differences across Europe masked genetic differentiation for BMI”. I would be skeptical of this -particularly, the genetics of obesity and overweight are not well understood, and distinct from the genetic differences behind normal BMI. It seems to me there is room for some populations to have a higher frequency of generalised obesity protective variants than others (better satiety / appetite response to food, improved insulin regulation, etc.), specifically having the effect of reducing accumulation of fat mass beyond the healthy range, even if they do not have variants that make a low BMI likely by stretching lean mass out over a taller skeletal frame.

  11. @ohwilleke
    The shoe that I am waiting to see drop is the recommendation of a Mediterranean diet, in which one of the main validating tests was conducted involving Spanish women.

    While the traditional Mediterranean diet has been shown, beyond question, to be beneficial in people with Mediterranean ancestry, it is not at all obvious to me that these benefits are equally great for people whose ancestry is remote from that region of the world (e.g. Scandinavians or Koreans).

    One significant difference between Med populations and others is the rate of APOe4 carries. It is very low in Southern Europe but higher in Northern Europe. As a heterozygote I am keenly interested in the optimal diet for me.

  12. @Supersnail
    I have 23amdme - is there a simple way for me to figure out if I have the 'fish oil is good' variant from their available data? I'm a bit of a noob at this.

    I don’t know the answer but one day I expect that’s exactly the kind of readout you could get with lists of good and bad foods for you personally.

  13. […] article: Greenlandic Inuit show genetic signatures of diet and climate adaptation. see also Your Genes Are What You Eat from […]

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