Epigenetics: Marrying genetics and environment in autism research?

Funny how these few simple words can create so much tension. Down the years just about every area of health and disease has witnessed the grudge match that is nature or nurture. Obesity:  food intake, or differences in the genes controlling how energy is used and stored? Heart disease: poor lifestyle choices, or genetic differences in our navigation of modern living? The list goes on and on and on in this often polarized debate.

Autism has, and continues, to have its own genes vs. environment debate. Indeed this debate has, perhaps above all others, contributed to quite a lot of the heated discussions in autism circles down the years on what is and isn’t autism in terms of aetiology and pathology. “It’s genetic,” say the twin studies. “No its not,” say the environmental camp, the two extremes sandwiched between various shades of gene-environment interactions in-between.

In this post, I want to talk about another player in the genes / environment arena – epigenetics – an area which might provide an olive branch between the two heavyweights, where foes might even become friends.

What is epigenetics?

Well, think about DNA – the genetic code that makes us who we are. There used to be a time when genes were thought to be everything. DNA was fixed and inside the DNA code were the answers to health, disease, mortality… everything. Nations spent millions, nay billions of dollars, pounds, euros on deciphering the secrets of DNA, with the promise of markers for disease and tailored treatment regimes. It all seemed so simple.

Except it wasn’t. Life never is.

Turns out that your genome might not be your final destiny after all. That DNA stuff, or at least how it is expressed, might be as modifiable as lots of other biological systems in the body. Switches such as methylation, acetylation and phosphorylation entered the dictionary and the ‘histone code’ [1] made an appearance quickly followed by the almost forgotten concept of Lamarckism (an organism can pass on characteristics that it acquired during its lifetime to its offspring).

In recent times we hear that even twins, identical twins, who share the same DNA, have differences in their epigenetic profile at birth [2]. With autism in mind, one wonders how this might fit in with the recent spate of research suggesting that heritability in autism is not necessarily as straight forward as we’ve all been led to believe [3].

How does epigenetics make adversaries like genes and environment kiss and make up?

Well the processes governing those DNA modifying factors might have a lot to do with environment. That recent twin study by Gordon and colleagues [2] suggested that the intrauterine environment might be one of the first places our DNA is influenced. As that warm and safe environment gives way to a lifetime exposure to the big wide world, factors such as diet [4], physical activity [5] even our socio-economic status [6] might further contribute to modifying the expression of our genes. If true, there’s a lesson for government policy in some of that research.

It’s still very early days for epigenetics and even earlier days for research into epigentics and autism. The histone code grows and grows in complexity as our knowledge of the number of possible modifications to genetic expression becomes more extensive. The science of epigenetics raises some interesting questions about how we could all potentially modify our “risk” of disease and general health.

Again with autism in mind, I immediately think back to the collected works of people like Jill James and their suggestion of hypomethylation of DNA in people with autism [7] and their parents [8]. The requirement for further investigation seems paramount if only to ascertain whether this is a central relationship to the presence of autism or merely an artefact.

Some final questions: could we alter such parameters via diet and/or supplementation with various vitamins and minerals? [9] What about the overall picture of methylation in cases of autism, subgroups of cases of autism, outside of what is already known? [10] Are we perhaps looking at the possibility of new ways of remediating such methylation issues and what would be the onwards effects to the presentation of conditions like autism?

Still lots of questions to be answered but at least the distance between genetics and environment might not be quite as great as we all first thought. The “Let’s get ready to rumble!” attitude of genes vs. environment might be replaced by “Let’s be friends.”?


[1] Jenuwein T. & Allis CD.  Translating the histone code. Science. 2001; 293: 1074-1080.

[2] Gordon L. et al. Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence. Genome Research. July 16: DOI: 10.1101/gr.136598.111

[3] Hallmayer J. et al. Genetic heritability and shared environmental factors among twin pairs with autism. Archives of General Psychiatry. 2011; 68: 1095-1102.

[4] Niculescu MD. & Zeisel SH. Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. The Journal of Nutrition. 2002; 132: 2333-2335.

[5] Lim U. & Song MA. Dietary and lifestyle factors of DNA methylation. Methods in Molecular Biology. 2012; 863: 359-376.

[6] McGuiness D. et al. Socio-economic status is associated with epigenetic differences in the pSoBid cohort. International Journal of Epidemiology. 2012; 41: 151-160.

[7] James SJ. et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. The American Journal of Clinical Nutrition. 2004; 80: 1611-1617.

[8] James SJ. et al. Abnormal transmethylation/transsulfuration metabolism and DNA hypomethylation among parents of children with autism. Journal of Autism & Developmental Disorders. 2008; 38: 1966-1975.

[9] Adams JB. et al. Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatrics. 2011; 11: 111.

[10] Shulha HP. et al. Epigenetic signatures of autism: trimethylated H3K4 landscapes in prefrontal neurons. Archives of General Psychiatry. 2012; 69: 314-324.

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