Tuesday, January 4, 2011

Nature + Nurture: Epigentics and Illness

Medical Alert PendantWe are constantly bombarded with references to growing epidemics of many types of illnesses and disorders- autism, hypothyroidism, diabetes, psoriasis, etc.. Some people argue it is a sign of the decline of our society and the overwhelming bad choices people are making. Some claim it is genetic, and the impact of modern medicine which allows "impacted" individuals to survive and pass on their genes.
The truth is that it is probably a combination of these factors, mediated by epigenetics- the impact of environment, stress and chemistry on gene expression without any change in DNA at all. This is an area only recently starting to gain the attention it deserves and we are far from real clinical, much less societal understanding.

A recent Scientific American article on the problems caused by the limitations of categorizations of the DSM manual and difficulties in tracing mental illness to its genetic roots danced around the issue of epigenetics, but handled it badly.

Consider the following excerpt:
How can these assertions be explained? In fairness to Robins and Guze, they could not have imagined the extraordinary genetic complexity that produces the risk of many common human ills, including mental disorders. What this means is that common mental disorders appear to be due to different combinations of genes in different families, acting in combination with epigenetics -- gene expression varies even if the underlying DNA sequence is the same -- and non-genetic factors.

In some families, genetic risk for mental disorders seems to be due to many, perhaps hundreds, of small variations in DNA sequence -- often single “letters” in the DNA code. Each may cause a very small increment in risk, but, in infelicitous combinations, can lead to illness. In other families, there may be background genetic risk, but the coup de grace arrives in the form of a relatively large DNA deletion, duplication, or rearrangement. Such “copy number variants” may occur de novo in apparently sporadic cases of schizophrenia or autism.


Note that although the first paragraph mentions the impact of epigenetics, the following sentences go on to talk about actual changes to the DNA. All inquiry into epigenetic controls and the impact of this on tracing genetics is avoided.

In truth, epigenetics is one of the last great mysteries in the study of illness transmission. For decades we have argued Nature versus Nurture.. debating the impact of genes over lifestyle choices in illness. But the truth is that for many illnesses (especially chronic illnesses- autoimmune diseases and mental illnesses large amongst them), the combination of genes, lifestyle and environment is the most important and hardest to categorize. Making things even more complicated, recent research is indicating that it is not just YOUR lifestyle and choices that impact you, but those of your parents and even GrandParents which can impact your health.

The good news is that there is a move to fund more research on epigenetics ( chronic illnesses are expensive, so the ROI can be argued). Just this year, the NIH issued a new series of grants to fund research into the impact of epigenetics in chronic illness. If you have one of these diseases ( as I do), will epigenetic research cure you? Unlikely. At best, we will find ways to modulate the impact of the disorder. But what it can do is break the cycle of illness being passed from generation to generation. If your children can be impacted, your grandchildren or great grandchildren might be disease free. This long term thinking is critical to breaking these cycles.


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