Genetics and Obesity

In my medical anthropology class, we’ve been reading Gina Kolata’s Rethinking Thin: The New Science of Weight Loss and the Myths and Realities of Dieting.  Kolata argues for a biological approach to obesity, that weight is largely under genetic control and that there is no ideal diet which is going to help all people lose weight.  In other words, Kolata is taking up the “nature” side of the nature/nurture debate, with a direct critique of the idea that if overweight people could simply use their willpower and follow the age-old recommendation of eat less and exercise more, they would be ideally thin like the beautiful people we see on television—the Brad Pitts and Angelina Jolies of the world. 

Kolata sums up these points in a very amusing interview on The Colbert Report.  As Fat Fu summarizes about Kolata, “you can actually learn something about the state of the science. And which don’t conclude with exhortations to diet or insinuations that fat people are lazy and ignorant. In fact she doesn’t think diets work.” 

I like Kolata’s book, which is why I assigned it in my class.  And I certainly see the weight of the evidence as supporting many of her main points: heritability and biological regulation of body weight, as well as the absurdity of an “ideal diet” that will simply work for everyone (that’s called ideology, folks).  But Kolata gives us an approach that recreates the mind/body and culture/biology dichotomies, and resorts to a genetic determinism that both obscures the genetics and doesn’t leave much room for anthropology.  For example, she uses one study, a classic one by Stunkard et al. in 1990, to tell us that “70 percent of the variation in people’s weight’s may be accounted for by inheritance,” which is greater heritability than with “mental illness, breast cancer or heart disease.” 

I’ll admit, I am not the biggest fan of twin studies.  They are generally done in western populations without much variance in environment or development and with relatively homogenous populations.  In public, these researchers generally claim the higher range of heritability estimates.  And perhaps most bothersome, these studies seem to provide us with a “why” that is not really there—“genetic” becomes tantamount to cause. 


I have to lecture on the human biology of weight and obesity on Tuesday, so I’ve decided to put together something like my “lecture notes” here on the blog.  I am planning to cover four areas on Tuesday—genetics, weight set points, hunger and appetite, and “will power”—and will hopefully cover most of those by Tuesday.  This time it will be genetics. 

In a recent review (open access pdf available), Farooqi and O’Rahilly (2007) confirm that “heritable factors are likely to be responsible for 45-75% of the inter-individual variation in body mass index.”  Maes et al. in a 1997 review found that “genetic factors explained 50 to 90% of the variance in BMI.”  Thus, variation in the data is greater than implied by Kolata.  And if we’re cautious scientists, we could take the lower estimates as the ones supported by all the science, so we’re talking about roughly 50% heritability. 

And what accounts for this relatively high heritability?  Is it some “obese” gene?  What I do find striking in these discussions is one simply fact that is generally left out.  We know height is one of the most heritable traits we have, in the range of 60-80% heritability (see this Scientific American article) with some estimates going into the 80-90% range in Western populations.  Since BMI is calculated by an individual’s weight divided by the square of their height, one might reasonably assume that height drives a lot of the heritability in body mass index. 

That said, more direct measures of adiposity have indicated high heritabilities for both total and regional fat in two studies that I saw (Malis et al. 2005; Carey et al. 1996).  So the weight side of the BMI equation also appears to be shaped genetically.  But my basic point holds—there is greater variation in the heritability estimates than often presented by genetic researchers and science writers who have a stake in making an argument to the public. 

Moreover, lifetime variation in BMI matters, and matters a lot, both in terms of the health impact and in terms of how environment can impact body weight.  For example, here’s an underappreciated fact about twins.  Pietiläinen et al. (2002) found that “[e]ven in monozygotic twins who share their genetic background, the initially larger twin tended to remain larger, demonstrating the long-lasting effects of fetal environment on final body size.”  As Kuzawa et al. (2007) argue (pdf), fetal programming and uterine environment play a significant role in the development of obesity.  It’s not simply genetics, end of story. 

Indeed, I found it interesting that heritability estimates for BMI went down over the lifespan in one study.  Height stays relatively stable, but both weight and BMI drop in “heritability” as a person ages.  As the researchers write, “nonshared environmental variance increased with age.”  So, in terms of what is driving changes in BMI over the lifespan, one could use the fetal programming and the drop-off in heritability to argue that development and environment are the determinative factors, rather than genetics. 

I’m not actually saying that.  Here’s what I would say: Partitioning the world into genes and environment is a pretty crude strategy, and misses out on how things actually work.  Heritability estimates are not absolute figures but a rough guide to what sorts of traits are more heritable than others.  Height, for example, appears more heritable than weight. 

Also, saying something is genetic doesn’t mean you are analyzing the “difference that makes a difference.”  For example, language ability is surely largely genetic—after all, other species don’t speak full-blown languages, only humans.  However, what really matters in today’s world is what language you speak—English versus Spanish versus Mandarin versus Arabic versus Persian. 

So is obesity a problem of species differences, that humans are relatively fat compared to other species and now live in an “obesogenic” environment?  Or is obesity a problem of cultural variations, of patterns of development and of eating, of historical environments that push sugar and other profit-oriented products?  Myself, I’d take the Super Size Me version—that it is the everyday dimensions of obesity, and not solely the genetic dimensions of obesity, that play a more determinative role in who has a problem or not. 

Do those everyday dimensions play out against significant biological variation?  Most definitely yes.  Can we use our understanding of that variation to understand that “will power” or the “perfect” diet won’t be as effective for most people on the “wrong” side of that variation?  Here I’ll offer a more qualified yes, because this question, unlike the first one, frames the problem as nature versus nurture.  And obesity involves both nature and nurture and their significant interactions. 

Molecular genetic and biological mechanism research actually point to significant variation in “obesity” that is important.  A small percentage of obese individuals have “genetic obesity syndromes” (Farooqi & O’Rahilly 2007), for example, congenital leptin deficiency.  So it’s certainly not a one-size fits all approach.  However, this is precisely what the measurement of BMI does, give a number to a person irrespective of age, gender, muscle-building activities, or any number of other things found to shape BMI scores.

In reviewing the genetic research, what I did find striking is the conclusion that in most cases, obesity appears to be driven more by regulation of appetite and energy intake (Farooqi & O’Rahilly 2007).  As these authors write, “The genetic defects found to date all impair satiety, affecting the function of appetite control centres in the brain rather than being due to a ‘slow metabolism.’  This indicates that we must think of human food intake not as an entirely voluntarily controllable phenomenon but one driven by powerful biological signals from relatively primitive brain areas.  When these basic signaling mechanisms are severely disrupted, it is very difficult to overcome the drive to eat (38).”

Kolata’s book is filled with stories of people who successfully lose weight and then gain it back, driven by hunger.  Even though from the outside it might appear that they are not hungry—how could they be, all that extra weight?—their bodies respond as if they are hungry, as if they don’t have enough energy or even that they are starving.  It is one of the most convincing parts of her book, how she brings together the research evidence showing how heavier subjects react to weight loss like thin people put on starvation diets and the descriptions of struggles with weight loss and the powerful urges to eat described by the people in her book.

7 thoughts on “Genetics and Obesity

  1. Brought here by the pingback. I disagree with a lot of your conclusions but I love how you think. This was a thoughtful, informed piece. A pleasant rarity, and your students are lucky to have you.

    My disagreements. Yes, Kolata and the molecular biologists are giving us the tidy “no loose ends” version. And there are a lot of loose ends out there. But that’s true of any nature/nurture debate. And the evidence that weight is physiologically regulated, heritable, and that weight loss strategies don’t really work, while not bulletproof, are so strong – especially when compared to the degree to which most of us have been convinced of the exact opposite – that it’s understandable that she would present the most forceful case she could without burying herself in the muck that any nature/nurture debate engenders.

    You’re also misstating her case a little. Her ultimate argument isn’t that it’s all genes or that environment is unimportant, it’s a much more carefully worded and circumspect claim that “you may not be able to be arbitrarily thin.” Which I think is the very least you can say given the evidence.

    You’re doing a lot of very interesting picking at the margins of the argument (some of which I enthusiastically agree with, some of which I don’t). And while I think pulling at those threads is necessary and important, and there are deep philosphical issues to contend with, I gotta say. You risk missing the forest for the trees. Yes, environment matters. Yes, nature/nurture is a quagmire. But weight is not just 0.8 or 0.7 or 0.5 heritable. It’s REALLY heritable. No, really.

    What Kolata and the molecular biologists are trying to say is not that biology is destiny, but for some traits biology is more destiny than it is for others. And weight is one of those things for which it’s definitely more destiny. And that’s hard to get across with numbers. On its own just saying that a given trait is 50% heritable or 80% heritable is kind of meaningless – for one thing people interpret the number any way they want. “50% of fat people are fat because of lifestyle.” Or “50% of your weight is genes, 50% is McDonalds.” “If we ate paleolithic we’d be 50% thinner.” (It reminds me of the joke from The Hitchhiker’s Guide: What’s the meaning of life? 42. Now you have to go back
    and figure out what the question was. The heritability index is an excessively precise answer to a question we can’t remember anymore.)

    Here’s my unscientific approach. I know you don’t like twin studies, but it’s twins. In one of my posts on fat fu (‘twins”) I linked to a gallery of photos from a twin festival. I think they give you a visceral feel for just what a heritability index of 0.70 or 0.80 (or 0.50 if you prefer) really means in the real world. I don’t think it’s possible to look at those pictures and not at least begin to see the problem with nitpicking to death the bald fact that stares you in the face – that weight is, yes, incredibly heritable. And honestly, I think people for whom this is all academic or mathematical need to look at them as a reality check. Those photos don’t erase environmental influences but I think they put bounds and context on how much you can expect nurture to explain or “fix” human variation.

    Kolata’s also countering a group of people who are so singleminded about making the nurture case that they haven’t even noticed that they’ve thrown under the bus -and backed over several times – the people they’re hoping to “help.” It’s one thing to argue that high fructose corn syrup has an impact on weight, or that exercise is helpful – it’s an entirely different thing to completely discount physiology, genetics and human variability and allow millions of people to be demonized and scapegoated in the global war on fat.

    Because the real philosophical question we’re wrestling with is not so much how much can we blame on nature and how much on environment, but why do we construct certain traits in a moralizing way and others as morally neutral? Autism and schizophrenia are good case studies, because genetic models were important for shifting the focus away from models which blamed parental neglect and rearing (nurture). But for both of these disorders, the heritability studies are actually pretty mixed, and show much lower heritability than for fat. If somebody had wanted to pick the “nature” argument apart for either disorder and toss blame back on the parents they would have been in a much stronger position than we are when it comes to fat.

    The comparison is important, because at the moment not only are parents being chastised for their children’s weight, there’s talk (at least from the fringes) about prosecuting parents of fat children or having fat children removed from their parents’ homes (which has been done in rare cases in the U.S. and U.K). We’re very much in the situation with fat that we were in the past with children who were autistic. Actually we’re in a much worse situation since we’re in the middle of a global hysteria about weight and it’s unclear to what extremes that will drive public policy.

  2. A couple of great posts; thanks both to Daniel and to Fatfu. I’d also direct your attention to a recent article in the New England Journal of Medicine on the way social networks affect likelihood of obesity:
    Christakis NA, Fowler JH. 2007. “The spread of obesity in a large social network over 32 years.” New England Journal of Medicine. 357(4): 370-379.
    There’s an abstract of the piece here: http://content.nejm.org/cgi/content/short/357/4/370. There’s also a brief discussion of it here on the blog, Healthcare Economist: http://healthcare-economist.com/2008/03/24/the-spread-of-obesity-in-social-networks/

    I hear what Fatfu is saying, and I understand also the activist agenda; both the key point Fatfu makes and the agenda are important. But from my perspective as a researcher on exercise, neurology, skill, and sometimes even evolution, I have a different view. I don’t buy the Supersize Me scenario in one sense; I think that, given what would have been normal levels of exercise even 100 years ago, the all-MacDonalds diet might (MIGHT) not have been unhealthy for humans (although some of the health effects in that movie freaked me out). That is, in cases like the Inuit, we know human groups that have gotten what can only be considered shockingly ‘bad diets,’ by modern dietitians’ standards, who still didn’t have the health problems we associate with obesity. Usually, researchers look to something in the diet to explain why people who ate high quantities of animal fat or red meat or unvarying diets didn’t get health problems; was it fish oil or nuts or some other magic ingredient.

    But the overwhelming difference, to me, is sedentarism. Our society is, in my opinion, so different from others NOT because of what we eat — humans have eaten all sorts of things and seldom consult with a reputable nutritionist before doing so — but because of how little we move. Estimates on movement in foraging societies are always very high; I’ve recently read 12 miles per day, average, but I’ve also been looking at extreme cases, and they are stunning. Native American groups who ran very long distances as part of festivals and inter-group competitions, distances in the hundreds of miles.

    Even in agricultural societies, people also moved a hell of a lot; it wasn’t just foraging. A researcher stuck pedometers on Amish people, a group not known for its low-fat diet or for their obesity problems, and found that people were walking miles every day. One guy apparently was walking around 25 miles a day behind a plow, which wouldn’t have been easy miles. My wife’s grandmother just told me that she and her brothers and sisters used to walk 4.5 miles to and from school — 9 miles a day — and that was before they started to play sports or have fun.

    As Drs. Rainer Hambrecht and Stephan Gielen argued in an essay in The Lancet in 2005, the amount of energy expended by kilogram of body weight is estimated to be less than 40% today of what it was in ‘the Paleolithic.’ (I’m a little uncomfortable with the assumptions about time periods we can’t actually do research in, but the comparative data makes this assertion pretty hard to contest.) Contemporary estimates are that 40% of the US population does NO exercise. We have created an environment in which movement is not necessary when, in most human niches, people are constantly moving. We all know the stories; people walking miles to collect wood or carry heavy jars of water, hunters stalking prey for miles, people walking for days to travel. It’s just not something most of us do.

    Given this staggering difference in activity levels, the question I would ask is not, how do genes make some people obese, but rather how on earth does anyone NOT get obese at low activity levels? We know that body fat itself is pretty energetically cheap to keep on the body; it doesn’t add too much to the body’s ability (or need) to metabolize calories, so once you’ve got, you pretty much get to keep the fat for free. I’m not trying to get all preachy, as Fatfu suggests is the usual route, but rather to point out that, for me, the research question is not, ‘what is the gene for obesity?’ but rather, what the hell is it about the people who DON’T get obese given that we’re in such an odd situation for our physiology?

    People sometimes suggest that over-eating is a kind of pathology, often suggesting that it has to do with psychological problems. They also imply that satiety is a problem; some people are genetically predisposed not to feel satisfied when they eat. I don’t know. But I do know that animals are pretty prone to over-eating, too, as my increasingly fat Labrador retriever and two cats attest. And I know that our horses, if they manage to get their teeth on a bag of feed, will gladly eat until they make themselves very sick. We had a real scare with one of them due to over-eating. And we have many ethnographic and travelers’ accounts of populations with virtually no levels of obesity eating tremendous amounts of food when they have it; I read in grad school a Jesuit missionaries account of how Canadian Indians ate when they got ahold of game during the winter, and they would blow away the most impressive binges in McD’s in terms of an orgy of gluttony. But then again, the group bordered on starvation in between successful hunts in the winter (thanks Marshall Sahlins for assigning that one).

    I agree with Fatfu that there’s a bit of an obesity hysteria, but when you start to look at the difference in activity levels in our environments, it seems pretty clear (at least to me) what the ’cause’ of weight gain is. The point is clearly not to ‘go back’; who would want to have whole communities periodically starving, or force everyone to work at hard manual labor. Moralizing the issue — suggesting that fat people are weak or immoral, or that the parents of fat kids are irresponsible — is hardly helpful (or even accurate), but I also think that the argument that people are just genetically predestined to be obese is equally inaccurate (and probably unhelpful). It may influence the growing social stigma placed upon obesity, but it’s hardly the whole picture of what is leading to changes in our bodies.

    Understanding this global picture of the body and energy reframes the question, for me, about genetic contributions to obesity. Seeing obesity narrowly, bounded by Western ideals of body type and moral assumptions about food, seems to make ‘the obesity problem’ distorted and individual, and it leads to questions like, ‘what are the genes that contribute to obesity?’ Clearly, given this screwed up environment, some people may have genes that, somehow, buck the almost inevitable energy imbalance due to sedentary life. Or maybe there’s something psychological about those who stay thin in spite of rocky road ice cream, Coca-cola, pizza, and family holiday feasts that makes them deviant. But for me, at least, knowing the scorecard in a broader perspective makes me more interested in what is odd about those who stay thin given this situation.

    Reference

    Hambrecht, Rainer, and Stephan Gielen. 2005. Essay Hunter-gatherer to sedentary lifestyle. Lancet 366: S60–S61.

  3. Fatfu, thanks for the detailed comment with thought-out arguments. Greg and I have hoped to spark debate, really the exchange of ideas, and I truly appreciate you coming over here to share your insights. In one sense, I think we are arguing about two different things. I don’t particularly like biological determinism, it doesn’t have a good historical track record when applied to social issues and doesn’t always help us think about complex human phenomena. So some of that is coming up in my post.

    In my take on your comment, you are reacting against an equally determinative assumption–of willpower and an ability to control body shape/thinness–as well as against the stigma accompanying weight in the US. And I actually agree with you. So I applaud when you say about Kolata’s argument, “it’s a much more carefully worded and circumspect claim that “you may not be able to be arbitrarily thin”.” The moralizing side of things is particularly pernicious at times from both the science and the popular side, and even the moralizing gets naturalized (see my critique of Pinker back in January). So for me it was great to see you come over and really bring that out.

    I am planning to post in the near future on some of the physiology and variability, so I hope you check back in to make sure I am not veering too far to one side or another.

  4. Gregdowney writes: Given this staggering difference in activity levels, the question I would ask is not, how do genes make some people obese, but rather how on earth does anyone NOT get obese at low activity levels?

    That’s where the inherited factors come in. Everyone anecdotally knows of individuals who eat many calories and move hardly at all, yet are slender or “average.” Why does Evolution 101 fly out of our heads when we talk about fatness? Human populations aren’t genetically uniform.

    What I’m missing here is a discussion of *why* we would have genes leading to fatness in the first place. It seems to me that populations would support a range of genes, where some people would be able to withstand starvation better than others. Speculatively, it may be that the first diet (“I weigh 150, but I’m so fat, I have to weigh 135”) provides the biological “cue” that starvation is imminent, thus triggering particular “thrifty” genetic responses in some.

    This is a different situation than individuals with specifically damaged genes (whether they involve leptin or not.) Thus you have “freak show” type television shows about extremely large individuals, with the covert message that if “we” keep eating “junk food,” “we” are all going to look “like them.” But as Kolata points out in her book, naturally “average” people who participated in overeating experiments did gain some weight, but lost it when they reverted to their normal eating patterns. So there is something (most likely) genetic going on with these extremely large people that is possibly *different* from having a “thrifty” constitution.

  5. Stefanie —
    I think you totally missed my point. But I’m sure my students next semester in Anthro 151, Human evolution and diversity, will be relieved that you’ve put me back on track to finding the evolutionary thought that ‘flew out of my head’…

    When I asked Anne Fausto-Sterling about a related issue a few years ago, she told me that she suspected that our brains and bodies were so different from prehistoric humans because of such radical change (I assumed in behavior and environment) that she found most evolutionary explanations for modern behavior patterns to be dubious. I guess I share her dubiousness. One of the principal ways that we seem to differ so profoundly from our ancestors that comparison fails us, in my opinion, is this pattern of inactivity and sedentary life. At least in my view, sedentary life is so UNLIKE anything our ancestors might have encountered that coming up with evolutionary scenarios that include it are suspect.

    What I’m saying is that sedentary existence is such a radically different environment than what evolutionary psychologists suggest is humanity’s ‘environment of evolutionary adaptation’ that all bets are off as to how we will respond physiologically. Put a microbe in a glass of Coca-Cola, and it will react, but the environment is so alien to anything it would conceivably encounter outside that glass that it’s difficult to say whether its activities are any realistic predictor of what that microbe would have been like in a different environment. The problem with studying humans is that it’s very hard to find anyone living outside the glass of Coca-Cola when it comes to certain environmental characteristics.

  6. Pingback: The Anthropology of Obesity | Neuroanthropology

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s