Biological insights from 108 schizophrenia-associated genetic loci:
Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
This publication is accompanied by a massive grant to the Broad Institute for the purposes of making discoveries in the field of psychiatric genomics. Eric Lander is a brilliant scientist, but boy can he bring in the dollars. Psychiatric genetics has been around for a while, from the days of linkage studies to association analysis. But it’s been plagued by inability to replicate positive findings, strongly suggestive of issues of sample sizes too small to have the power to answer the questions being posed robustly. The people associated with the Broad Institute are smart. Hopefully they don’t have to worry about adding a line to their CVs with studies they’re not totally sure of. With these sorts of sample sizes there is a chance that they can brute force their way past some of the expected problems of finding genuine novel genetic associations when a trait his highly polygenic.
Finally, perhaps with some of the $650 million allocated to this research they could publish in journals that are open access or pay Nature/Science/Cell to have them open access? If you look at the author list it’s enormous. These projects in the future are going to involve many different research groups, and a substantial portion of peoples’ careers. It is probably optimal that this research is widely distributed partly to stimulate interest from those who are thinking about a career in science.
Addendum: I can see why they don’t call it ‘psycho-genomics.’ But it would be fun.
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