Wiring the Brain

--> A paper published today represents a true landmark in psychiatric genetics. It reports results of a genome-wide association study (GWAS) of schizophrenia, involving 36,989 cases and 113,075 controls. Assembling this sample required collaboration on a massive scale, with over 300 authors involved. This huge sample gives unprecedented statistical power to detect genetic variants that predispose to disease, even if their individual effects on risk are tiny. The study reports 108 regions of the genome where genetic differences affect risk of disease. This achievement is rightly being widely celebrated and reported, but what do these results really mean? GWAS look at sites in the genome where the particular base in the DNA sequence is variable – it might sometimes be an “A”, other times a “T”, for example. There are millions of such sites in the human genome (which comprises over 3 billion bases of sequence). Each such site represents a mutation that happened some ...

Disorders such as autism, schizophrenia and epilepsy each affect about 1% of the population and are therefore defined as “common disorders”. But are they really? I mean, they are clearly really that common, but are they really “disorders”? Are they natural categories that reflect some shared underlying etiology or are they simply groupings based on sets of shared symptoms? Genetics is providing an answer to that question and demonstrating that so-called “common disorders” are really collections of rare disorders with similar symptoms. This represents a complete paradigm shift in psychiatry, the full ramifications of which have yet to be appreciated. We have known for decades of examples of rare genetic syndromes that can include symptoms of autism spectrum disorder (such as Fragile X syndrome or Rett syndrome ) or of schizophrenia (such as velo-cardio facial syndrome , now called 22q11 deletion syndrome), while epilepsy is a known symptom of many genomic di...