Neurological disorders appear genetically distinct from one another and from psychiatric disorders

Science Paper Graph

As part of the Brainstorm Consortium, UK DRI researchers have played a role in starting to re-shape how we think about disorders of the brain. If we can uncover the genetic influences and patterns of overlap or distinctiveness between different disorders, then we might be able to better understand the root causes of these conditions — and potentially identify specific mechanisms appropriate for tailored treatments.

The Brainstorm Consortium is an international collaborative effort, led by Ben Neale and Aiden Corvin at the Broad Institute, that includes over 600 institutions across the globe. Its main goal is to bring together vast amounts of genetic data to understand similarities and differences, at the genetic level, among various types of brain diseases (both psychiatric and neurologic). Many UK DRI researchers are part of the consortium, including our PIs Jose Bras (UCL), Rita Guerreiro (UCL), Nick Fox (UCL), Valentina Escott-Price (Cardiff) and David Rubinstein (Cambridge).

Published in Science, a new study from the group takes the broadest look yet at how genetic variation relates to brain disorders. The team determined that psychiatric disorders share many genetic variants, while neurological disorders (such as Parkinson’s, Alzheimer’s and multiple sclerosis) appear more distinct both from one another and from psychiatric disorders.

The Guerreiro-Bras lab at the UK DRI at UCL generate genetic data on Parkinson's disease that was important to include in the Brainstorm Consortium study. The group were involved from early on as part of the Brainstorm Consortium’s steering and the analytical groups. They performed analyses and guided data interpretation, particularly those including neurodegenerative phenotypes.

Dr Jose Bras, Programme Lead at the UK DRI at UCL, explains the power of the consortium:

"In total, this study included genetic data of over 1.1 million individuals, with over a quarter being affected by one of these diseases. These are staggering numbers that would not be achievable without such a collaborative effort." 

The researchers were surprised to note that genetic factors predisposing individuals to certain psychiatric disorders — namely anorexia, autism, bipolar, and OCD — were significantly correlated with factors associated with higher childhood cognitive measures, including more years of education and college attainment. Neurological disorders, however, particularly Alzheimer’s and stroke, were negatively correlated with those same cognitive measures. The teams will need more work and even larger sample sizes to understand these connections.

Understanding the genetic similarities and differences between these diseases means that we are closer to being able to characterise diseases in much more detail than current clinical classes. This has future implications, for example, in individual selection for trials, molecular therapeutic interventions or personalised therapies. Dr Jose Bras, UK DRI at UCL

The consortia have made their GWAS data accessible online, either freely available for download or by application. They plan to examine additional traits and genetic variants to explore these patterns further, aiming to discover the relevant mechanisms and pathways that underlie and potentially link these disorders.

Funding for this study was provided in part by the National Institutes of Health, the Orion Farmos Research Foundation, and the Fannie and John Hertz Foundation. 

Paper: The Brainstorm Consortium. Analysis of shared heritability in common disorders of the brain. Science. Online June 21, 2018. DOI: 10.1126/science.aap8757 

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