Genetics vs. environment in obesity discussion

I started this as a comment to this thread, but perhaps this is enough for its own spin-off discussion. IndianCowboy said:

I'm not denying the influence of these genes on one's ability to maintain a certain weight. I'm not even denying the size of their influence, but one thing that bothers me is that many researchers, bloggers, reporters, whatever impute more into the findings than they should.

And I agree with that. Clearly it's not all genetic, and diet + exercise play a large role. Additionally, any one genetic locus (which is what's usually found in a study) alone is unlikely to be a big factor by itself. But despite what Hank keeps claiming, it's not really disputed that there is a genetic factor as well, and that's important to recognize both from the epidemiology side of things (to understand why so many people are overweight), as well as from a treatment standpoint. Simply telling someone who's overweight to "eat less and exercise more," while clearly good advice, can be frustrating when they know they already *are* eating less and exercising more than many of their thin friends, for example.

I think it was also IndianCowboy who'd mentioned "penetrance" on his own blog when discussing obesity. And that's yet another thing to consider as well. The authors suggest this SNP may affect expression of the downstream gene (or may be a marker for differences in expression of it). Other genetic or environmental influences may also affect this expression. [Warning: personal anecdote time] For instance, I'm a person who rarely feels full. I can eat and eat and never get that "I'm stuffed" feeling. (Great for Thanksgiving dinners; not so great for everyday meals). My sister is the same way. I never realized this was, well, out of the ordinary until I became pregnant with my daughter. Not only did I have horrible morning sickness, but I also felt that "I'm stuffed" feeling after only a few bites of food. I ended up losing 13 pounds during my first trimester from the combination of the nausea and inability to eat real meals. Clearly my genetics hadn't changed, but my hormones had, likely affecting expression of the genes that cause one to feel "full." (According to this, I probably don't make as much PYY as people who normally feel full after a meal). I could easily see how this could lend itself to obesity. I learned growing up what a normal portion size was, and I didn't (and don't) eat a lot of high-calorie, high-fat fast food, but what about people who feel this way and regularly eat 2 Big Macs and a large order of fries in a sitting? And worse, were taught to eat that way from childhood? It can be very difficult to train one's self to eat less when you still feel hungry after a meal.

I also have a fairly sluggish metabolism. If I average more than about 1200 calories a day, I gain weight. This is despite hitting the gym 3-4 times a week and running around after my kids (not to mention all the walking around campus), so I'm a pretty active person. For whatever reason, I just don't seem to burn calories very quickly. This was probably a good trait 500 or 10,000 years ago, but now it's unfortunate for me if I want to maintain my weight. My mother-in-law, on the other hand, has had 8 children and still is a size 6, despite eating practically every other meal cooked in lard. (OK, maybe not quite that bad, but I swear I gain weight just *smelling* the food at her house).

Obviously this is all anecdotal, but since it takes quite a lot for me to be somewhat thin (and we're not even talking "skinny" here--my own BMI is around 21-2, so around the middle range of "normal"), I feel a lot of sympathy for anyone who struggles with their weight, and it can be condescending to tell them "just eat less" or "just exercise more." I know that simply doesn't do it for me, and if I were less stubborn, I'd just say "to hell with it" and not bother. I think that learning what affects weight at the genetic level--and ideally, finding something to help deal with it there in addition to diet and exercise--would do a lot for those who lose motivation when simple diet and exercise don't work.