
The Thin Gene - jseliger
http://www.nytimes.com/2016/11/25/opinion/sunday/the-thin-gene.html?action=click&pgtype=Homepage&clickSource=story-heading&module=opinion-c-col-right-region&region=opinion-c-col-right-region&WT.nav=opinion-c-col-right-region
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jrapdx3
This is a very interesting and well-written article. The subject of particular
importance to me for a couple reasons.

One is professional. I ran an obesity treatment clinic for several years but
it's a clinically important area of practice that fascinated me as far back as
undergraduate years. The article correctly states that treatment for obesity
is largely unsuccessful, the tools and methods have barely made a dent in
terms of solutions.

Surgical procedures for obesity are crude measures to be sure, very frequently
associated with severe nutritional deficiencies that are hard to manage. IMO
at best surgery is a desperate "last straw" means to stave off fatal outcome,
worthy in that sense, but hardly a prescription for the 99% of the population
who are not in that condition.

Fact is there's no medical problem more complex than obesity. Hundreds of
genetic factors are connected to the many metabolic, endocrine, and immune
system alterations from normal found in the obese. There are profound
correlations with behavioral disorders and metabolic abnormalities associated
with obesity.

An issue in the research that I'll need to learn more about is whether obese
patients actually have excess aprosin. The woman who is the subject of the
article is deficient, but that doesn't necessarily mean that blocking the
hormone will have a favorable effect in obesity. Also, it's apparent the
hormone has multiple effects, antagonizing the hormone effect could well cause
undesirable outcomes.

I can easily empathize with the woman's plight. While I'm not suffering
anything like the devastating condition portrayed, I've always been on the
underweight end of the scale. Even as I go forward into my "mature" years,
this characteristic hasn't changed. Tall and very thin body build isn't
optimal for health and social reasons, then again people say I look good for
my age, so it's not the same set of problems as the article describes.

The lesson I take from the article and real-world observations is the
incredibly vast range of individual variability among humans, not that we'd
have any doubt about it based on even casual observation. But it's a reality
we have to constantly remind ourselves about. Our preference of putting things
into categories blinds us to the limits of categorizing. Truth is on close
examination humans will inevitably fall between the cracks wherever we put the
categorical boundaries.

~~~
tropo
Don't forget viruses. There are viruses that are unusually common in really
huge people.

~~~
jcoffland
Can you cite any proof of this?

~~~
smallnamespace
Not directly related to viruses, but here's a study that shows that gut
bacteria from thin people will make mice thinner:

[http://www.nytimes.com/2013/09/06/health/gut-bacteria-
from-t...](http://www.nytimes.com/2013/09/06/health/gut-bacteria-from-thin-
humans-can-slim-mice-down.html)

There are a lot of knobs that control metabolism, and scientists are only
starting to figure it out.

------
gwern
On a related note, the first GWAS hit for anorexia nervosa has been announced
just today:

"Genome-Wide Association Study Reveals First Locus for Anorexia Nervosa and
Metabolic Correlations", Duncan et al 2016
[http://biorxiv.org/content/early/2016/11/25/088815](http://biorxiv.org/content/early/2016/11/25/088815)

"Anorexia nervosa (AN) is a serious eating disorder characterized by
restriction of energy intake relative to requirements, resulting in abnormally
low body weight. It has a lifetime prevalence of approximately 1%,
disproportionately affects females(1,2), and has no well replicated evidence
of effective pharmacological or psychological treatments despite high
morbidity and mortality(2). Twin studies support a genetic basis for the
observed aggregation of AN in families(3), with heritability estimates of
48%-74%(4). Although initial genome-wide association studies (GWASs) were
underpowered(5,6), evidence suggested that signals for AN would be detected
with increased power(5). We present a GWAS of 3,495 AN cases and 10,982
controls with one genome-wide significant locus (index variant rs4622308,
p=4.3x10-9) in a region (chr12:56,372,585-56,482,185) which includes six
genes. The SNP-chip heritability (h_SNP^2) of AN from these data is 0.20
(SE=0.02), suggesting that a substantial fraction of the twin-based
heritability stems from common genetic variation. Using these GWAS results, we
also find significant positive genetic correlations with schizophrenia,
neuroticism, educational attainment, and HDL cholesterol, and significant
negative genetic correlations with body mass, insulin, glucose, and lipid
phenotypes. Our results support the reconceptualization of AN as a disorder
with both psychiatric and metabolic components."

More specifically, with _endocrine_ components
([https://twitter.com/psychgenomics/status/802254444154892289](https://twitter.com/psychgenomics/status/802254444154892289)).

(Of course, you don't need any GWAS hits to do research on the genetics of
anorexia nervosa or to look for
[https://en.wikipedia.org/wiki/Genetic_correlation](https://en.wikipedia.org/wiki/Genetic_correlation)
with other traits, since that can be done with polygenic scores sans any hits
or with twin/family studies, but it does help motivate research.)

------
nealabq
Here's an idea: a site for people with unusual genes, good or bad. They can
describe why they're unusual, and in some cases get asked for more details or
even for a DNA sample. All voluntary of course. Forums for people with similar
conditions, questions about long term affects or attempted remedies. Feed the
data to an AI. Maybe monetize with subscriptions to medical researchers.

~~~
therein
I had this idea a few years ago.

~~~
mixedCase
Have you implemented it?

~~~
therein
I started looking into it but I was busy with something else at the time.

I had talked to the mods of /r/nootropics and also the owners of a few
domestic suppliers/storefronts and they were definitely very interested. I
mean, it is clear that if we are as a community serious about self-
experimentation, we have to find a way to consolidate the results of our
individual n=1 studies.

------
goblin89
FBN1, the gene also behind Marfan syndrome[0].

[0]
[https://en.wikipedia.org/wiki/Marfan_syndrome](https://en.wikipedia.org/wiki/Marfan_syndrome)

------
lucidguppy
I feel like this is a submarine for gastric bypass surgery. I've noticed that
in the UK there seems to be a lot more push for these through documentaries
(US has them too).

I was able to lose a lot of weight on a whole foods plant based diet. Its a
permanent change. With the SAD diet being the dominant form of nutrition -
very few people can maintain a healthy weight (25%).

------
packrat386
A modern day Erysicthon

------
jcoffland
> For instance, the contestants on the “Biggest Loser” TV show became paragons
> of self-control; some shed more than 100 pounds, something very few of us
> could ever achieve. And yet a recent study showed that even these incredibly
> disciplined dieters gained all the weight back.

This study has now become quite famous but it should be noted that the
participants where given no help after the show and not surprisingly went back
to their old habits.

> “Unfortunately, many contestants are unable to find or afford adequate
> ongoing support with exercise doctors, psychologists, sleep specialists, and
> trainers — and that’s something we all need to work hard to change,” -- from
> [http://mobile.nytimes.com/2016/05/02/health/biggest-loser-
> we...](http://mobile.nytimes.com/2016/05/02/health/biggest-loser-weight-
> loss.html)

One participant did manage to keep most of the weight off but only through
persistence.

I feel for those with real genetic disorders but for most of us we _can_ lose
weight _and_ keep it off. New York Times articles which tell us that it's not
our fault, that it's genetics, leptin, metabolism, aging, etc. are exceedingly
popular but for most of the population these are just excuses.

Here us how you do it. Drop your daily calories to a very low but still safe
level (1500 or less) by counting and writing down the calories of everything
you eat. Do this for at least two months. Then start an exercise cycle where
you do an hour of highly strenuous cardio at least five days a week. Continue
for at least two months. Then go back to dieting. Repeat until you hit your
goal weight. Then you can relax until your weight creeps up 10-15 lbs at which
point you start the cycle again. This is what it takes for an average person
in our modern society to stay healthy.

If this seems extreme consider that for thousands of years most of our
ancestors endured much more physical exertion on a regular basis and on less
calories. We live in a world of excess which is in itself a sufficient
explanation for our obesity problem. Excluding of course those few people who
actually suffer from weight related diseases.

~~~
smallnamespace
> New York Times articles which tell us that it's not our fault, that it's
> genetics, leptin, metabolism, aging, etc. are exceedingly popular but for
> most of the population these are just excuses.

The science explains _why_ some people have to _work so hard to be thin_ ,
while others like myself can eat whatever I want whenever I want and still
remain rail-thin.

If I can eat 3k calories a day and be skinny, while someone else needs to drop
to 1500 calories to not be fat, it seems the height of unfairness to blame
that person for being in that situation.

~~~
jcoffland
If the science explained anything sufficiently we'd have drugs that treat
obesity.

Excess is enough to explain the problem.

~~~
smallnamespace
Science has yet to cure cancer--would argue that all cancer is caused by
excess?

------
Neliquat
The solution for obesity is self control. Any other band aid is just a crutch.
I wish we could move past 'genetics' and take personal responsibility.

~~~
nxc18
While having strong self control is of course important, there are differences
between individuals that you're not considering. Many of the people who give
this self-control argument have never had theirs tested - it is hard to not
eat a lot when you are acutely hungry and eating doesn't stop that, for
example.

Also note that your statement doesn't really work in the general case. I have
friends who are extremely skinny (to the point that it distresses them) who
are trying to get bigger. It doesn't matter how many thousands of calories
they eat, how excellent their nutrition is, they struggle to gain anything -
and that is someone who naturally only wants to eat ~1500 calories per day. Is
it lack of self-control that they don't spend every waking moment stuffing in
high-calorie food despite not being hungry?

~~~
avar
Have these friends of yours tried talking to e.g. a powerlifting or
bodybuilding coach? It's pretty easy to get on a structured low-effort diet to
gain weight, and muscle mass with some exercise thrown in.

Getting above 1500 calories isn't some desperate effort of "spend[ing] every
waking moment stuffing in high-calorie food". It's a couple of protein shakes
a day that take you a couple of minutes to prepare & slurp down.

Eating enough _can_ be a very difficult logistical problem, but not at the
1500 calorie level, but at something like a >5000 calorie level where you're a
professional strongman or powerlifter, or someone like Michael Phelps eating
8000 calories a day.

~~~
nxc18
He was drinking lots of protein shakes... It wasn't that he was maxing out at
1500, it is that he didn't seem to want much more than that. With the amount
of protein shakes and other things he was eating, anyone else would have
gained fat at the very least. He lifted, too, but he wasn't that dedicated, so
idk.

~~~
avar
Sounds like your friend went through a half-assed ad-hoc diet & exercise
program, which unsurprisingly didn't yield results.

Extracting any useful data from "I have friends who..." is impossible. People
are notoriously bad at self-evaluating things like their food intake or
exercise regiment, and on top of that they're prone to present themselves in a
good light.

You'll find few people who'll say "Yeah I could have lost/gained weight, but I
lack the dedication and impulse control to manage my diet & exercise", even
though that may be the description that best explains the situation.

