Genetics of common neurological diseases
This page is maintained as a historical record and is no longer being updated.
This page is being kept as a historical record of the research conducted at the Sanger Institute. This page is no longer being updated and was last edited Summer 2013.
Please note: This page is no longer being updated.
From Autumn 2007 to Summer 2013, Professor Aarno led the Genomics of common neurological disorders group at the Wellcome Trust Sanger Institute which mainly investigated the genetic predisposition of traits affecting the Central Nervous System, particularly migraine, epilepsy, schizophrenia and autism.
Professor Aarno Palotie is faculty member at the Broad Institute of MIT and Harvard and the Massachusetts General Hospital, Center for Human Genetic Research in Boston MA and is the Research Director of the Human Genomics Program at the Institute for Molecular Medicine, FIMM in Helsinki, Finland. From Autumn 2007 to Summer 2013, Professor Aarno led the Genomics of common neurological disorders group at the Wellcome Trust Sanger Institute which mainly investigated the genetic predisposition of traits affecting the Central Nervous System, particularly migraine, epilepsy, schizophrenia and autism.
The team searched for both common and low-frequency variations in the DNA sequence of people who have migraine, epilepsy and autism, and seeked to link these variants to susceptibility to these conditions. Many of the projects were based on studying a geographically isolated population – the Finnish founder population. Using large well-characterised sample sets from this group and others enabled the discovery of several new regions of DNA associated with disease. In collaboration with a number of international groups, the team used genome-wide association studies to identify the first robust variant associated with common forms of migraine. The wealth of multiple studies with large sample sets enabled the group to use different study designs for variant identification and verification and for the estimation of the size of the effect contributed by the variants.
The recent boom of genome-wide association studies (GWAS) has had a major impact on our current view of genetic susceptibility to common traits and complex disorders. Although many neurological disorders have a strong genetic component, relatively few associations have been found so far. Despite extensive research, the detailed molecular background of the genetic susceptibility to these traits remains relatively unclear.
The overall goal of our group is to improve our understanding of the genetic mechanisms underlying neurological and neurodevelopmental traits with a particular focus on migraine, epilepsy, schizophrenia and autism. These conditions have a considerable impact on public health:
- migraine ranks among the 20 most disabling diseases and has been estimated as the most costly neurological disorder in Europe
- 1 in 50 people in the UK will have some form of epilepsy at some time in their life
- 1 in 100 people over the age of 18 will be affected by schizophrenia
- 2-4 in 1000 children will be affected by autism
It is hoped that developing a deeper understanding of the genetic background of these conditions will lead to improved diagnosis and treatment.
We recently published results from a genome-wide association study of migraine with aura, in collaboration with six major headache research centres in Europe and Australia. This study identified a susceptibility variant on chromosome 8q that is potentially linked to glutamate neurotransmitter regulation. We are now following up this initial result in different migraine subtypes, migraine sufferers from population cohorts and individuals suffering from chronic pain.
To identify potential high-penetrance variants predisposing to familial forms of migraine and epilepsy, we have begun whole-exome sequencing of 2000 familial cases. This multicentre collaboration should greatly improve our understanding of the genetic architecture underlying these nervous system disorders.
Unique populations have also shed light on possible cellular differences in autism. By combining data from genome-wide association studies and expression profiles of peripheral blood leukocytes from autism patients from an isolated region of Finland, we identified two biological pathways associated with autism: nervous system development and cell-to-cell signalling and interaction. Whole-exome sequencing of individuals from these families is now being carried out as part of the UK10K project.
UK10K: Aims to uncover the role of rare genetic variants in health and human by studying the genetic code of 10,000 people in fine detail. Our group is specifically involved in the neurodevelopmental arm of the project aiming to sequence the exomes of 3000 schizophrenia and autism samples.
1000Genomes: A deep catalogue of human genetic variation.
ENGAGE: European Network of Genetic and Genomic Epidemiology. ENGAGE aims to translate the wealth of data emerging from large-scale research in genetic and genomic epidemiology from European (and other) population cohorts into information relevant to future clinical applications.
International Headache Genetics Consortium: The consortium combines groups interested in the genetic basis on headache disorders.
Finnish Intracranial Aneurysm (IA) Research Consortium: The consortium brings together groups interested in the pathophsiology of intracranial aneurysms.
Geuvadis: A European medical sequencing consortium funded by the European Commission under the 7th Framework programme, the GEUVADIS Project brings together 17 partners including academic institutes and private companies, from 7 different countries. The Consortium is committed to share data, experience and expertise in high throughput sequencing to better understand the meaning of our genome, both in health and disease.
Synsys: Synsys stands for ‘Synaptic Systems’. The consortium assembles well-established international expertise spanning the academic and SME sectors to provide a technology workflow of experimental and computational scientists, to embark on the next step in synapse structure, function, modelling for future drug discovery enabling the combat of brain diseases.