The Grand Locus / Life for statistical sciences



Is there a gene for alcoholism? (1)

This is usually the next thing I hear when I say that I am a geneticist. Behind this question and its variants lies a profound and natural interrogration, which could be phrased as "how much of me is the product of my genes?" I made a habit of not answering that question but instead, highlight its inaneness by lecturing people about genetics. So, for once, and exclusively on my blog, here is the tl;dr answer: no, there is not. Now comes the lecture about genetics.

I will start with mental retardation — unrelated with my opinion of those claims, really — and more precisely with the fragile X syndrome. James Watson, the co-discoverer of the structure of DNA and the pioneer of the Human Genome Project declared:

I think it was the first triumph of the Human Genome Project. With fragile X we've got just one protein missing, so it's a simple problem. So, you know, if I were going to work on something with the thought that I were going to solve it, oh boy, I'd work on fragile X.

In other words, there seems to be a gene for mental retardation. The incidence of the fragile X syndrome is around 0.025% of the US population, which makes it an extremely common genetic disease, compared to others. The sickness holds its name from an observation dating from the 80's showing that patients and carriers have an X chromosome that appreared to be broken under the microscope. This turned out to be an artifact of the preparation, the sickness itself is caused by mutations of the gene FMR1. What progress have we made since James Watson's declaration with that simple problem? Well, not much, really. FMR1 itself has nothing to do with the brain, but its loss has a wide range of effects on other genes. So the problem is more complex than it looked.

That was thirty years of planetary effort on a simple problem in a nutshell. The fragile X syndrome, a simple problem that represents only 1 case of mental retardation out of 40. Now let's talk about alcoholism. The incidence is around 8.5% of the US population, which makes it a much more heterogeneous (and difficult to measure) condition than mental retardation. What is the name of the gene that would cause it, you know, the one that they keep talking about in the media?

Actually nobody can tell. The claims that there is a gene for alcoholism (or heterosexuality, or other) usually come from genome association studies. It is important to understand that this kind of evidence is not causal, and that no experiment nor animal model supports them. All it says is that a particular sequence is found more often than expected by pure chance among people diagnosed with alcoholism. But this sequence does not have to be a gene. Most of the time, it is a SNP (single nucleotide polymorphism), i.e. a nucleotide that simply happens to be different between different people. The functions of those SNPs are usually not known. Most of them are neutral in the sense that there is no detectable difference whatsoever if you have one or the other variant.

But if it is not random, it must play a role, right? Well, not really. First, it is an accepted rule in the scientific community that 5% of the studies can be false (which makes me think that I have to discuss this in more detail in a later post). So, if twenty laboratories embark on proving that alcoholism is a genetic disease, one of them should come to that conclusion. Second, not random does not mean highly informative. A SNP allele present in 51% of alcoholic and 50% of the non alcoholic could easily qualify as gene for alcoholism. Finally, in The fallacy of (in)dependence I explained that non-independence, which is at the heart of the claims for the existence of genes of alcoholism, says something about the sampling of the phenomena, not about their causes. In such studies, so much depends on who is considered alcoholic, and how patients were sampled, that it takes some guts to make the bald statements that we sometimes see in the media.

To wrap up the discussion about genes and alcoholism, I will simply say that the studies that keep claiming to discover genes for such and such complex behavior are not serious. The example of the fragile X syndrome shows how difficult it is to really understand what mutations do to our brain, even when the conditions are optimal and when the best teams in the world work on the subject for 30 years. Behavior is simply too complex for today's genetics.

But will we ever find such genes? Is it theoretically possible to predict what will happen to us by knowing our genes? That's what I will discuss in my next post.

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