“Lifestyle and genes are not the only factors that shape disease risk, and factors and exposures before, during and after birth can help pre-program much of our adult health,” said investigator Robert Yolken, M.D., a neuro-virologist at Johns Hopkins Children’s Center.

Maternal infections and other inflammatory disorders during pregnancy have long been linked to greater risk for schizophrenia in the offspring but, the Swedish and U.S. investigators say, this is the first study that points to maternal food sensitivity as a possible culprit in the development of such disorders.

Two words: environmental damage

See:

(1) Whitacre, J.M. and A. Bender, Degeneracy: a design principle for achieving robustness and evolvability. Journal of Theoretical Biology, 2010. 263(1): p. 143-53.

(2) Mason, P.H., Degeneracy at Multiple Levels of Complexity. Biological Theory, 2010. 5(3): p. 277-288.

From what I have seen re: PTSD studies and twin data, heritability is given as 50%. But that is not in fact the case. We know from general population genetic studies that about 20% of a population is susceptible to PTSD and yet only 1/2 those are affected.

OTOH in high stress war zones reports of the % of troops affected runs in the 20 to 25% range. About what you would expect if 100% of the susceptible get enough stress.

Twin studies do not in fact control for environment. As far as I can tell.

I’m sure it can be done (or done better), but that is currently not the case. IMO. I only know this because the study of PTSD is a hobby of mine. So I’m not deeply conversant with the general field of genetics and heritability.

If there are cases where a rare mutation in a gene occurs along with a phenotype of autism (or schizophrenia, or ADHD) multiple times, then it doesn’t seem that far off to conjecture that this mutation was necessary for the phenotype, in those individuals. Whether it’s sufficient is up for debate–that may be where environmental effects come in.

This is all a very phenomenological type of “why”–when piece X breaks, phenotype Y can result. This single-gene causality sheds little light, however, on why it makes sense that the system breaks in certain characteristic ways rather than others. This is even more true when it is seen that the same mutations can show up in multiple different disorders. While it may be a small step to suggest that had gene X not mutated, uncommon phenotype Y would probably be absent, a model that can robustly predict whether phenotype Y or Z occurs based solely on knowledge of a few mutations X1, X2, etc. is much more difficult. Even more so, if you try to predict the manifestation of a spectrum disorder, i.e. whether the autism will involve speech difficulty or hyperlexia, for instance–and these are the things that really have meaning for what special accommodations or interventions are necessary.

Things like growth patterns and resource trade-offs are much more likely to capture the failure modes as a whole. Biological systems clearly seem to malfunction in a very different way from human machines. If a brake fluid line is ruptured in a car, it will not cause the steering to become more accurate. The most adaptive we can get with designs is to incorporate redundancy, which delays the consequences of progressive malfunction. Probably the most fascinating characteristic of biological systems, in my opinion, is their ability to “get by with what they have”. Yes, there are things like congenital blindness and deafness where there is simple absence of a trait, but more often there are both extreme losses of function and gains of function in the same disorder.

It is probably more apt to think of an organism like an ecosystem where loss of one species causes die-offs of some species and overgrowths of others. True understanding of biological phenotypes will only come about by understanding the interconnectedness of this “ecosystem”, which is much farther off than “lacking X correlates with end result Y”.

Is that really the right way to look at all this?

Some have noted that all the complexities of genetic interactions have not yet been teased out. Throw in the environment and there are a LOT more threads to untangle.

Maybe that didn’t come out quite right. I didn’t mean that you were overselling a particular finding. I mean that EVERYONE oversells these findings. If tomorrow scientists discover that a gene raises the risk of Disease X by 10% the headline the next day will be “Scientists Find Gene That Causes Disease X”. It’s easy to become cynical.

In contrast, previous associations with common SNPs, which supposedly contribute only a tiny increase in risk alone but a large effect in aggregate, have not held up over time. In my opinion, that is because that model of the genetic architecture of illness is not correct – that does not imply (at all) that the illness is not primarily genetic.

“We identified POTENTIALLY causative de novo events in 4 out of 20 probands, particularly among more severely affected individuals, in FOXP1, GRIN2B, SCN1A and LAMC3.”

You wrote that these 4 mutations cause Autism and yet the study abstract says that they are “potentially causitive”.

Over the last 20 years the only common denominator I’ve seen in the field of genetics is oversold findings.

While it’s certainly possible that these 4 genes trigger Autism I wouldn’t bet on it. If history is any guide future research will suggest that they are merely associated with an increased risk of disease or the original discovery was a false positive.

I’m sure if you asked the studies authors they would tell you that the connection between obesity and Autism is in some way related to harmful inflammation or a secondary consequence of harmful inflammation.

The next time you read that a disease is associated with obesity think associated with inflammation. The two are connected like pepperoni and cheese.