Showing posts from 2018

If genomics is the answer, what's the question? A commentary on PsychENCODE

There was much excitement in the press and in the psychiatric research community recently as a flurry of papers was published, presenting the work of the PsychENCODE project. This project, involving the work of many labs, aimed to deploy the powerful tools of genomics to dissect the landscape of gene regulation in the human brain, with the ultimate goal of revealing the molecular underpinnings of psychiatric disease. Genome-wide association studies ( GWAS ) have revealed hundreds of common genetic variants that are statistically associated with increased risk of psychiatric disorders, such as schizophrenia, ADHD, bipolar disorder, and, to a lesser extent, autism. What they have not revealed is how such variants increase risk of disease. The PsychENCODE project aimed to generate a set of data that would allow researchers to answer that question. There are a number of challenges in going from identification of an associated risk variant to elucid

How free is our will?

If we all come with pre-wired traits and with adaptations based on our past experiences, are our decisions ever truly free?  When I give talks demonstrating that we all have innate psychological predispositions – traits that influence our behaviour across our lifetimes – I often get asked what implications this has for free will. If our behaviours are affected in some way by our genes or by the way our brains are wired, doesn’t that mean that we’re really not that free after all? The answer depends, I think, on the kind of free will you’re after and on an understanding of the mechanisms by which we make choices. And let me say at the outset that we do make choices. The idea that neuroscience has somehow done away with free will altogether or proven that it is an illusion is nonsense. All neuroscience has shown is that when you are making decisions, things are happening in your brain. This is, to put it mildly, not a surprise – where else would

Life after GWAS – where to next, for psychiatric genetics?

GWAS ( genome-wide association studies ) for psychiatric illnesses may be about to become a victim of their own success. The idea behind these studies is that common genetic variation – ancient mutations that segregate in the population – may partly underlie the high heritability of common psychiatric and neurological disorders, such as schizophrenia, autism, epilepsy, ADHD, depression, and so on. The accumulating evidence from over ten years of GWAS strongly supports that idea, with many hundreds of such risk variants now having been identified. The problem is it’s not at all clear what to do with that information. GWAS are a method to carry out a kind of genetic epidemiology, based on a simple premise – if a particular genetic variant at some position in the genome (say an “A” base, as opposed to a “T” at position 236,456 on chromosome 9) – is associated with an increased risk of some condition, then the frequency of the “A” version should be higher in peo

Calibrating scientific skepticism – a wider look at the field of transgenerational epigenetics

I recently wrote a blogpost examining the supposed evidence for transgenerational epigenetic inheritance (TGEI) in humans. This focused specifically on a set of studies commonly cited as convincingly demonstrating the phenomenon whereby the experiences of one generation can have effects that are transmitted, through non-genetic means, to their offspring, and, more importantly, even to their grandchildren. Having examined what I considered to be the most prominent papers making these claims, I concluded that they do not in fact provide any evidence supporting that idea, as they are riddled with fatal methodological flaws. While the scope of that piece was limited to studies in humans, I have also previously considered animal studies making similar claims, which suffer from similar methodological flaws ( here and here ). My overall conclusion is that there is effectively no evidence for TGEI in humans (contrary to widespread belief) and very little in mammal