Saturday, November 07, 2009

Goodbye Genetics, Hello Epigenetics

For the first time in history, science now has tools that can definitively answer long-standing questions about the role of genetics as the cause of diseases.  So far, the results have been devastating for believers in genetic causality.  The better we can see, the less genetic causality we find.

I've previously summarized the minimalist findings of modern genetics research for a number of psychiatric disorders, including addiction, here and here in this blog, and in my book, Empowering Your Sober Self.

Now comes another blockbuster study, this time of schizophrenia, a disease commonly believed to have a strong genetic component.  According to the November issue of Scientific American, summarizing a recent report in Nature, "three crack teams of investigators pooled genomic data from 8,000 schizophrenics of European ancestry but could lay claim to only a handful of weak genetic risk markers."

By contrast, says the same article, epidemiologists have been able to find significant correlations between schizophrenia and environmental and cultural conditions.  Growing up as an immigrant or as a racial minority in a big city, particularly in densely populated and troubled neighborhoods, is a significant risk factor for the disease.

These studies have given a boost to the field of epigenetics -- the study of how environmental conditions evoke or overwrite genetic predispositions.  The primitive notion that our DNA is our destiny is giving way to the understanding that our genes do nothing until they are activated.  Environmental conditions (including not only the chemicals that enter our body but also the decisions we make, the people we hang with, and the stress we undergo) determine whether a gene gets turned on or off.  Our genetic array is like a keyboard, and our interaction with the world governs what melody gets played on it.

By coincidence, a recent issue of Counselor, the magazine for addiction professionals, features an article, "Epigenetics Has Come to the Addiction Field," by Mike Taleff, Ph.D.  Taleff's main point is that it's not genetics that makes a person an alcoholic or other addict.  It is the repeated consumption of alcohol and other drugs that programs a person's genetic material to crave the drug and prioritize its consumption.

This epigenetic understanding, says Taleff, can help a recovering person shed some common myths, such as the belief that "they are somehow morally, bad, defective, or otherwise flawed.  Often, this kind of thinking gets in the way of recovery."  Epigenetics teaches, by contrast, that becoming addicted "has little to do with your moral character."  Addiction is a result of the programming that addictive substances perform on your brain.

Many questions remain to be settled before science can claim that we have a comprehensive understanding of the causes of addiction.  But progress is being made.  For decades, addictionology was stuck in the belief that the alcoholic/addict's disorder was genetically programmed. Thanks to the enormous strides made by genetic science in the past decades, with the deciphering of the human genome and the subsequent advances, we can now say with considerable certainty that genetics supplies only a weak explanation at best. Now we need to turn our eyes toward the epigenetic factors:  environment, culture, and above all the neurochemical properties of the addictive substances themselves.


SteveMDFP said...

Unfortunately, there's a big logical flaw in the line of reasoning here. Difficulty in sorting out the precise mechanisms of genetic influence on addiction risk doesn't mean there isn't any (or isn't much). It only means that the genetic mechanisms are complex, multi-faceted, and probably poly-genetic.

The degree of influence of genetics on such traits is measurable. They are measured using twin studies, examining family history and personal development of addiction in identical twins raised separately vs together.

These studies consistently yield an estimate of 40% - 60% heritability of addiction.

In this context, failure to find a single or small number of genes does not mean that genetics are unimportant; they are clearly of great importance.

See, for further detail:

Sex Differences in the Genetic Risk for Alcoholism
Carol A. Prescott, Ph.D.
published by NIAAA

But the blog is outstanding. It's on my blogroll at:

Best wishes,

Steve Coulter, MD

Martin Nicolaus said...

I can't agree. Twin studies have grave methodological flaws, and "family history and personal development" studies are anecdotal at best. It's because of these well known limitations that the modern quantitative genomics studies have been undertaken. And the pattern they revealed has been rather consistent across a broad range of psychiatric disorders: genetic influences are weak, measurable in the single digits.

SteveMDFP said...

Actually, the situation is exactly like the heritability of athletic prowess. Multiple lines of evidence indicate a strong genetic component, but gene-level studies have come up empty-handed.

Tools to tease out mechanisms of heredity have always lagged far behind the ability to determine that heredity is present for a trait. Greger Mendel, after all, demonstrated the basics of genetics a century before science had any clue at all about DNA.

With such complex, multi-faceted, multi-etiologic conditions, I doubt that precise genetic mechanisms will ever be teased out. The theoretical challenges are daunting, and the practical applications are probably zero.

If a thousand different genetic mechanisms each convey a two-thousandth percent additional risk, there is no conceivable way to use this knowledge directly for any benefit.

The importance of the twin studies in these disorders is to confirm that biology plays an important role in these conditions.

Therefore, truly holistic treatment and prevention efforts must at least consider possibilities of biology-based interventions (e.g., medications), in addition to psychological and social ones.

Best wishes,

Steve Coulter, MD

Martin Nicolaus said...

Well, we have a choice. We can look at the actual genes, and come to the conclusion -- as the modern studies increasingly have done -- that the genes don't have all that much to do with the disorder. Or we can look at studies of twins, which methodologically rigorous critics consider junk science, and draw a tenuous thread of inferences that the genes "must" have been major causal factors.

Anonymous said...

40 to 60% is pretty indefinite. That, in and of itself, is enough to cast doubt upon assertions of 'great importance'
The evidence is far from clear and convincing. The necessary research has just begun.

Martin Nicolaus said...

In reply to Anonymous:

Actually, the "necessary research" has been done for many of the key areas in the past ten to twenty years. We've looked at the actual genes, like we've never been able to do before, and the answer is that genetic causality in these complex disorders and traits is minimal. What still needs to be done is to re-educate our brains to jettison the geneticist folklore and rethink the problems based on the evidence.