Monday, March 3, 2008

Genetics and Disease

There is a lot of confusion surrounding the role of genetics in health. It seems like every day the media have a new story about gene X or Y 'causing' obesity, diabetes or heart disease. There are some diseases that are strongly and clearly linked to a gene, such as the disease I study: spinocerebellar ataxia type 7. I do not believe that genetics are the cause of more than a slim minority of health problems however. Part of this is a semantic issue. How do you define the word 'cause'? It's a difficult question, but I'll give you an example of my reasoning and then we'll come back to it.

A classic and thoroughly studied example of genetic factors in disease can be found in the Pima indians of Arizona. Currently, this population eats a version of the American diet, high in refined and processed foods. It also has the highest prevalence of type II diabetes of any population on earth (much higher than the US average), and a very high rate of obesity. One viewpoint is that these people are genetically susceptible to obesity and diabetes, and thus their genes are the cause of their health problems.

However, if you walk across the national border to Mexico, you'll find another group of Pima indians. This population is genetically very similar to the Arizona Pima except they have low rates of obesity and diabetes. They eat a healthier, whole-foods, agriculture-based diet. Furthermore, 200 years ago, the Arizona Pima were healthy as well. So what's the cause of disease here? Strictly speaking, it's both genetics and lifestyle. Both of these factors are necessary for the health problems of the Arizona Pima. However, I think it's more helpful to think of lifestyle as the cause of disease, since that's the factor that changed.

The Pima are a useful analogy for the world in general. They are an extreme example of what has happened to many if not all modern societies. Thus, when we talk about the 'obesity gene' or the 'heart disease gene', it's misleading. It's only the 'obesity gene' in the context of a lifestyle to which we are not genetically adapted.

I do not believe that over half of paleolithic humans were overweight, or that 20% had serious blood glucose imbalances. In fact, studies of remaining populations living naturally and traditionally have shown that they are typically much healthier than industrialized humans. Yet here we are in the US, carrying the very same genes as our ancestors, sick as dogs. That's not all though: we're actually getting sicker. Obesity, diabetes, allergies and many other problems are on the rise, despite the fact that our genes haven't changed.

I conclude that genetics are only rarely the cause of disease, and that the vast majority of health problems in the US are lifestyle-related. Studies into the genetic factors that predispose us to common health problems are interesting, but they're a distraction from the real problems and the real solutions that are staring us in the face. These solutions are to promote a healthy diet, exercise, and effective stress management.


Aaron Blaisdell said...

I decided to go back and read some of your early posts, starting at the beginning. Not sure if you'll ever see this comment, but here goes...

We can say that genes play a direct causal role in health, just as they play a direct causal role in just about every trait (morphological, physiological, behavioral). But the nature of the role they play is under debate. The fact that every human (except in extremely rate cases) is born with a four chambered heart, and bilaterally symmetrical, etc. These are traits that have genetic determinants (without having DNA these traits would not develop), but the heritability of these traits is zero. Thanks to Fischer for clarifying the distinction between "caused by genes" and a genetically heritable trait. Heritability is the amount of variance in a trait that has a genetic component. Thus, heritability is the real issue and is what the media should be focusing on. Of course, we all know that the media, in attempting to bring us the cliff notes version of science (and everything) dumbs it down to the point of oversimplicity and inaccuracy.

Stephan Guyenet said...

Hi Aaron,

The first comment on this post! I basically see genetics (as it relates to idiopathic diseases) as determining your level of susceptibility to stressors.

For example, your HLA alleles determine how you react to gluten. But back in hunter-gatherer times, there was no gluten so it was moot.

Anonymous said...

I'm doing the same thing, starting at the beginning and reading through.

I partly agree and partly disagree: for example one side of my family has a high proportion of sufferers from the consequences of insulin resistance up to and including Type 2 diabetes, the other does not - but they have an above average incidence of atypical depression.

Both sides of the family tend to die of cardiovascular disease, often at an advanced age, but almost no-one suffers cancer ever.

IME such familial disease patterns differing significantly from the population as a whole are far from uncommon, which suggests a genetic basis. The important bit is to determine what genes you may carry and how to NOT express them, which is where the environmental bit comes in.

Unknown said...


I think that is interesting about your family, but I don't think you got the point Stephan was trying to get across. To go back to the original Pima example: It does seem that the Pima are more susceptible to certain diseases, and that greater susceptibility would seem to be based on their genetic makeup. But are genetics the cause? Reread the original post.

jewiuqas said...

Genetics versus lifestyle. I often muse myself about the role of these two in determining one’s health history/prospects. You, Stephen, are inclined to accuse lifestyle in the first place for our illnesses. Don’t you think however, that genes themselves are also susceptible of degeneration? The fact is that some people living on a 100% western diet, with all the worse the term might involve, manage to avoid major health problems all their life long, some others, in spite of taking care of themselves, don’t. In my view, the pitfall of this thing with healthy lifestyle is just there: the effects don’t necessarily manifest themselves in the person who is abusing his health (or simply is ignorant, as more often the case is), but it will deteriorate the genes of his/her posterity. That is the reason why western nations (geography is increasingly losing its proper meaning in this context) are becoming sicker and sicker with every successive generation, I reckon. I would cite but one example: some African people living in western countries and eating the worst type of modern food still have healthy teeth. I suppose Europeans got their genes deteriorate over time as they have been longer on western diet. I don’t know if you follow me and see where I want to get. I just think, that genetic and lifestyle factors cannot be fully separated, because lifestyle can influence hereditary properties in the long run.

jewiuqas said...

Dear Stephan,

I have just realized that I have misspelt your name. I beg your pardon for that. I am a regular reader of your site; you helped me to understand some basic facts about nutrition.
May be you’ll find my previous comment a bit na├»ve, or lacking insight. As a matter of fact, I know very little about genetics. Maybe genes don’t change so quickly as to be responsible for the deterioration of health from generation to generation. But what is responsible than? If you keep a population on an un-altered bad quality diet for generations, will their general health stabilize itself on a certain (low) level, or will it get worse and worse? Now, if overall health of modern populations is declining, I can see but two possible explanations: either the quality of our foodstuffs is getting worse and worse, or the pernicious effects of a more or less unaltered diet are passed on to successive generations and thus getting accumulated in our genes. But again, I repeat, I don’t know much about genetics. Can some corporal defects be passed over to one’s progeny in some way other than via genes? For example let us take a couple suffering from deficiency of vitamin D, and having skeletal problems for this reason. Will they pass this illness on to their son? If yes, are the genes intact? As you can see, I am really a newbie in genetics. Your readers are quite enlightened, maybe doctors themselves, so you might find no interest in answering my questions.