A genome-wide association study or GWAS for short is basically a study in
which you get a large sample of individuals that have a particular
disorder or trait and a large sample of people who don't have that trait and
what it allows us to do is we genotype those people and we sort of slather
about a million markers across the entire genome and then we compare the
genomes of people with the illness to people without the illness and where
significant differences arise is where genes that influence risk for that
disorder might lie.
In its most basic sense this study confirms that there's a
genetic component to anorexia nervosa but it takes us one step further than
that what it's done is it's identified eight areas on the genome where genes
that influence risk for anorexia nervosa may lie now although this is a
breakthrough it's also just a beginning because we're anticipating that there
are going to be hundreds of genes associated with anorexia nervosa so
that's the first finding the second finding is really intriguing and this is
actually what we call genetic correlations so we took all of the
information underlying this GWAS for anorexia nervosa and we correlated it
with 447 other GWAS's of other traits from other psychiatric disorders to
metabolic phenotypes to educational attainment and a number of significant
finding significant correlations arose and the pattern of correlations is such
that there is very clear positive genetic correlations between anorexia
nervosa and other psychiatric disorders like obsessive-compulsive disorder
depression and anxiety disorders and in fact that genetic correlation with
obsessive-compulsive disorder is one of the strongest positive genetic
correlations in psychiatric genetics and the neat thing about that is it mirrors
what we see in the clinic so often we see people with anorexia who have OCD
depression and anxiety but basically the genes are
now telling us that what we're seeing is due to genetic factors which is a really
interesting outcome but we take it one step further so in addition other types
of genetic correlations that we saw are with a bunch of metabolic and
anthropometric or body measurement phenotypes so suddenly we see that
anorexia nervosa is not only a psychiatric disorder but it also has a
metabolic component and this is a novel finding from this study
so traditionally anorexia nervosa has been viewed primarily through a
psychological lens and now I think what we need to do is we need to add a second
lens and we need to start looking through that metabolic lens as well this
doesn't immediately tell us what the underlying biology is but it points
toward clear next steps of research that need to be done we need to understand
exactly what the metabolic component is and how it influences anorexia in the
interim one very important message is how critical it is to adequately
renourish people with anorexia nervosa especially in the United States we often
see that insurance companies will do eyes treatment prematurely so people
will be discharged from the hospital before their bodies have had an
opportunity to sort of react will abate or stabilize at a healthy weight and so
this suggests that getting the metabolism stabilized again might be a
very important in fact core component to recovery from anorexia nervosa.
One of the main principles behind GWAS is to elucidate biology what's the underlying
biology of the illness in this case anorexia nervosa and we've identified
these first eight genes and we have some hints about how they're starting to a
sword in pathways but as we increase our sample size and identify more genes
those pathways are going to become more clear and then what we're hoping to do
is engage our physiologist friends our neuroscientist friends our
pharmacogenetic friends and start actually developing medications
that directly target the underlying biology of the illness
because right now we have no medications that are effective in the treatment of
anorexia nervosa.
so I think there are three limitations of this study and even
though people here 17,000 people with anorexia it makes them think that it's a
big study it's actually just a moderately sized GWAS so we're
actually aiming to get a hundred thousand participants so sample size is
one of the limitations a second limitations is we don't have enough men
and we really want to understand whether the same genes that influence risk for
anorexia and girls and in women also influence risk for anorexia and men so
as we expand our sample size we're gonna have to work really hard to recruit men
to participate and then the third thing is this study was primarily on people of
European ancestry because when we started the study we actually didn't
have the techniques to analyze more diverse samples but now we have those
techniques so as we increase our sample size we're going to sample widely and
we're going to make sure we have representation from all racial and
ethnic categories.
A really important thing for people to keep in mind when
they interpret the results of this study is that genetics are not destiny so when
we're born we get 50% of our genes from our mother and 50% of our genes from our
father in that mix of genes you're gonna have a certain number of risk genes for
anorexia nervosa but you're also can have some buffering genes or genes that
make it less likely for you to develop that illness and then plus we have to
throw in the environment so in the environment you have high risk
environmental situations that you also have buffering environmental situations
and it's those four buckets the risk genes buffering genes risk environment
and buffering environment that together make up your risk so it's very
complicated how at risk you are and who's at risk for developing this
illness.
The next study we're going to expand
beyond anorexia nervosa we're going to continue collecting individuals who had
anorexia nervosa but we're also going to broaden out to the other eating
disorders so we're going to be recruiting people to participate who
have bulimia nervosa and binge eating disorder and this study is called edgy
or the eating disorders genetics initiative and it's going to be easier
to participate in this one because for ANGI we had to collect blood from
everyone but technology has advanced in the last six years and now all we have
to do is spit into a tube and fill out some questionnaires online so stay tuned
we'll be launching EDGI soon and our goal is to get a hundred thousand
participants people who have had eating disorders at any time in their life.
Even though this is a starting point it is not too early for us to engage people
from other fields it would be wonderful to have people who really study
metabolism for their life for their career to start looking at these data
and see where we can go with it it's not too early to get people involved from
Pharma who are interested in drug discovery because one of the things that
we know especially from all of these genetic correlations is genetic
information about anorexia doesn't just tell us about anorexia it tells us about
all of these other psychiatric disorders that it's related to and now we know it
tells us about all sorts of metabolic traits as well so there are far-reaching
implications now that we can start delving deeper in on a biological level