Polygenic score for obesity. . .and?

Coverage of a recent study.

The adults with the highest risk scores weighed on average 13 kilograms more than those with the lowest scores, and they were 25 times as likely to be severely obese, or more than 45 kilograms overweight. “What’s striking is not just the weight,” says Sekar Kathiresan, a cardiologist and geneticist at Massachusetts General Hospital in Boston and the Broad Institute in Cambridge, Massachusetts, who led the study. “If you have a high risk score for obesity, you’re at high risk for heart attack, stroke, diabetes, hypertension, heart failure, and blood clots in the legs.”

And what else? The polygenic score is a result of a statistical fishing expedition. We do not know whether the genes in the score govern physical characteristics, such as metabolism and food preferences, or whether they affect psychological traits, such as conscientiousness. I would be willing to bet that a lot of it is the latter.

If my intuition is correct, then the “obesity score” would predict a lot of other behavioral traits as well. Propensity for getting into financial difficulty. Grades in school. etc.

10 thoughts on “Polygenic score for obesity. . .and?

  1. Markets are seen as a battle for customers’ money. But the biggest battle is for customers’ time.
    Worries about obesity lead to people being encouraged to spend their time doing nothing that creates value or generates pleasure (except reduction of fat), such as pumping iron in public gymnasia, doing exercises or running around in circles. Terrifying them into spending their time this way produces results, but an exercise pill would solve the problem far better. The problem there is that no one has produced one that actually works. This is not through want of trying. But the problem is simply one of putting atoms and molecules in the right place, and this seems only to be achievable by solutions of the running around in circles variety.
    Any new ideas are often greeted as being “fads”, such as various diets. The latest idea to have hit big business is biomics. A correlation between obesity and an individual’s biome seem to have been found, but whether changing the latter produces a dramatic result remains to be seen.

  2. We do know where the different genes are, and they are overwhelmingly in the brain. See Stephen Guyenet’s “The Hungry Brain”. That’s why these studies are powerful – they are an unbiased look at which parts of the human genome influence various potential human states.

  3. From the article “High- and low-risk individuals start to show significant differences in body weight at about 3 years of age”.

    Looks like there is more involved than a propensity for getting into financial difficulty poor study habits in school and some physical characteristics are being governed.

    • But do those same individuals track linearly with high/low risk over time, or do they change their relative positions as they go through puberty into adulthood? Looking in the aggregate, it would be easy to mark that the percentage of high risk people at age 3 was the same percentage of high risk people at age 40, but that doesn’t mean it was the same people.

      Just as a for instance, my dad was a tiny kid. Wrestled in the 95 lb weight class until his senior year of high school. In his sophomore year of college he grew 3-4″ and gained around 50 lbs. He did this while being a serious competitive miler. (He ran track and cross country.) By 50 he was 6’1″ and around 200 lbs, still a runner.
      In my case, I was 5’10” and 150 by 8th grade, and hit 6′ in the middle of undergrad. Now I am 6′ and 210 pounds on a good day. (Maybe less if I still ran regularly.)
      Now genetically, we are probably really close in terms of risk factors. Observationally we are damned near identical, and have been my whole life. But if you put 14 year old me next to 14 year old him, people would assume that he was my little brother, possibly 5-6 years younger.

      TL;DR people fluctuate wildly in their relative physical sizes within their age group from childhood to adult hood. I would be skeptical of a study that doesn’t follow the same people from youth to middle age yet claims that the genes predict relative sizes across age groups.

  4. I think the key is that the polygenetic score is a strong predictor of “severe obesity” (i.e. morbid obesity). I don’t think the causation/correlation distinction is important at this point and I don’t see any reason to be skeptical of the results.

    The important question, in my mind, is if there is any possible benefit to knowing the “severe obesity” risk for an individual through a genetic test before the BMI can be measured with a tape and a scale?

    It is my understanding that mortality rates start to increase at a BMI > 40 and increase linearly beyond that but the mortality risk is still less than smoking until the BMI > 50.

    So how does an early but not deterministic predictor of severe obesity help? It looks like an interesting new dimension for further research but I don’t see how it adds any actionable information to what we already have.

    • I like the idea of that, although if I am honest with myself it might just be co-correlated with how much time one spends studying, writing, and screwing around in front of a computer. 🙂

  5. Admittedly, I’m not an expert on obesity, but have read some on the topic and chatted with experts about it (nutritional researchers at NIH, leaders at The Obesity Society, a nonprofit research group). From what I’ve read and heard, obesity is complicated and involves multiple factors – physiological (e.g. hormonal malfunctions), psychophysical (brain chemistry), psychological (e.g., depression, anxiety), and social. In the latter case, one study demonstrated that people who socialize with overweight people (family and friends) tend to weigh more than others who socialize with the svelte. I have a recollection that this study was carefully done to sort out cause and effect but, unfortunately, I cannot remember the citation. The hypothesis was that socializing with overweight/obese associates contributed to making obesity socially acceptable. And compounding this medical and psychological problem is that being obese is revealed publicly, which leads to opprobrium and other adverse reactions from other people. As a counterexample, consider another “pandemic,” diabetes. One cannot tell whether another person has diabetes merely through visual observation. In sum, obesity is a complex problem and difficult to solve.

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