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October 3, 2016
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October 11, 2016
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Webpage:https://medicine.tcd.ie/neurology/

Research Field
  • genetics, genomics and molecular biology
  • neuroscience and mental health
  • bioengineering/medical devices
  • epidemiology/population health research
My WorkOur work focuses the exploration of disease heterogeneity in ALS. In 2006 we identified ALS9, caused by variants in ANG (Greenway Nature Genetics 2006) , and we have contributed to most European GWAS studies of ALS (van Rheenen Nature Genetics 2016) .We have shown that ALS rates are reduced in admixed populations, and that ancestral populations differ from one another in the frequency of known variants (Zaldivar Neurology 2009). We have a population based ALS Register that has ascertained all cases of ALS in Ireland over 22 years, now comprising extensive data from over 2200 patients and linked to a DNA bank of over 1100 cases and matched controls with with links to datasets across Europe and Latin America. We have shown that ALS and Schizophrenia are biologically linked (Byrne Ann Neurol 2013). We are whole genome sequencing “superfamilies” from 700 Irish ALS patients and 300 controls, and have access to 22000 whole genome sequences through the Project MinE Consortium. We have longitudnal 3T imaging from over 100 ALS patients and matched controls, and linked longitudinal spectral EEG recordings from 90 patients providing evidence of network disruption in ALS with correlation between structural MRI and spectral EEG
Outline of Potential Research projectsThe Irish population provides an ideal cohort with which to take a“precision medicine” approach towards Amyotrophic Lateral Sclerosis (ALS). Our research projects are designed explore disease heterogeneity within and across populations in Ireland, Europe and Latin America, and to undertake novel genotype phenotype studies, recognizing the likely importance of previously ignored genetic pleiotropy within extended kindreds, and discovering novel overlapping pathways in neurodegeneration and neuropsychiatric disease at clinical, neurophysiological and genomics levels.
Our existing population based studies of cognitive and behaviour involvement in ALS and our most recent demonstration of biological link between ALS and neuropsychiatric conditions in extended kindreds provide an innovative and previously unexplored basis for re-defining ALS as a genetically pleiotropic, multi domain neurodegenerative disorder of motor and extra motor pathways. This re-orientation opens many different and innovative approaches towards understanding neurodegenerative and neuropsychiatric disease, which can be fully developed by extensive population based phenotyping, detailed genealogical studies and modern genomics, working within the Irish group and with collaborators in Scotland, England, Holland, Italy, and Australia. Our projects also combine deep phenotyping and genomics work with advanced imaging and innovative signal processing data to explore the network disruption underlying the clinical manifestations of disease, and to generate reliable biomarkers within disease sub-phenotypes , defined clinically, and by advanced biostatistical processing and cluster analyses.