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

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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 people with the condition than pe…

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

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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 mammals more generally (with one very…

Grandma’s trauma – a critical appraisal of the evidence for transgenerational epigenetic inheritance in humans

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Can molecular memories of our ancestors’ experiences affect our own behaviour and physiology? That idea has certainly grabbed hold of the public imagination, under the banner of the seemingly ubiquitous buzzword “epigenetics”. Transgenerational epigenetic inheritance is the idea that a person’s experiences can somehow mark their genomes in ways that are passed on to their children and grandchildren. Those marks on the genome are then thought to influence gene expression and affect the behaviour and physiology of people who inherit them. 
The way this notion is referred to – both in popular pieces and in the scientific literature – you’d be forgiven for thinking it is an established fact in humans, based on mountains of consistent, compelling evidence. In fact, the opposite is true – it is based on the flimsiest of evidence from a very small number of studies with very small sample sizes and serious methodological flaws. [Note that there is, by contrast, very good evidence for this kind…