John Hardy

UCL Eastman Dental Institute, Londinium, England, United Kingdom

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Publications (788)7226.1 Total impact

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    ABSTRACT: Germ-line genetic control of gene expression occurs via expression quantitative trait loci (eQTLs). We present a large, exon-specific eQTL data set covering ten human brain regions. We found that cis-eQTL signals (within 1 Mb of their target gene) were numerous, and many acted heterogeneously among regions and exons. Co-regulation analysis of shared eQTL signals produced well-defined modules of region-specific co-regulated genes, in contrast to standard coexpression analysis of the same samples. We report cis-eQTL signals for 23.1% of catalogued genome-wide association study hits for adult-onset neurological disorders. The data set is publicly available via public data repositories and via http://www.braineac.org/. Our study increases our understanding of the regulation of gene expression in the human brain and will be of value to others pursuing functional follow-up of disease-associated variants.
    Nature Neuroscience 08/2014; 17(10). DOI:10.1038/nn.3801 · 14.98 Impact Factor
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    ABSTRACT: Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. Method: The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders. Results: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10-4), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01). Conclusions: Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.
    American Journal of Psychiatry 08/2014; 172(1). DOI:10.1176/appi.ajp.2014.13101306 · 13.56 Impact Factor
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    ABSTRACT: SQSTM1 mutations, coding for the p62 protein, were identified as a monogenic cause of Paget disease of bone and of amyotrophic lateral sclerosis. More recently, SQSTM1 mutations were identified in few families with frontotemporal dementia. We report a new family carrying SQSTM1 mutation and presenting with a clinical phenotype of speech apraxia or atypical behavioral disorders, associated with early visuo-contructional deficits. This study further supports the implication of SQSTM1 in frontotemporal dementia, and enlarges the phenotypic spectrum associated with SQSTM1 mutations.
    Journal of Alzheimer's disease: JAD 08/2014; DOI:10.3233/JAD-141512 · 3.61 Impact Factor
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    ABSTRACT: Our objective was to design a genotyping platform that would allow rapid genetic characterization of samples in the context of genetic mutations and risk factors associated with common neurodegenerative diseases. The platform needed to be relatively affordable, rapid to deploy, and use a common and accessible technology. Central to this project, we wanted to make the content of the platform open to any investigator without restriction. In designing this array we prioritized a number of types of genetic variability for inclusion, such as known risk alleles, disease-causing mutations, putative risk alleles, and other functionally important variants. The array was primarily designed to allow rapid screening of samples for disease-causing mutations and large population studies of risk factors. Notably, an explicit aim was to make this array widely available to facilitate data sharing across and within diseases. The resulting array, NeuroX, is a remarkably cost and time effective solution for high-quality genotyping. NeuroX comprises a backbone of standard Illumina exome content of approximately 240,000 variants, and over 24,000 custom content variants focusing on neurologic diseases. Data are generated at approximately $50-$60 per sample using a 12-sample format chip and regular Infinium infrastructure; thus, genotyping is rapid and accessible to many investigators. Here, we describe the design of NeuroX, discuss the utility of NeuroX in the analyses of rare and common risk variants, and present quality control metrics and a brief primer for the analysis of NeuroX derived data. Copyright © 2014. Published by Elsevier Inc.
  • JAMA Neurology 08/2014; 71(8):1052-1053. DOI:10.1001/jamaneurol.2014.1506 · 7.01 Impact Factor
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    ABSTRACT: We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation.
    Nature Genetics 07/2014; 46(9). DOI:10.1038/ng.3043 · 29.65 Impact Factor
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    ABSTRACT: α-Synuclein (SNCA) locus duplications are associated with variable clinical features and reduced penetrance but the reasons underlying this variability are unknown.
    JAMA Neurology 07/2014; 71(9). DOI:10.1001/jamaneurol.2014.994 · 7.01 Impact Factor
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    ABSTRACT: Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to Nasu-Hakola disease, Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and FTD-like syndrome without bone involvement. TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis. Whether and how TREM2 missense mutations affect TREM2 function is unclear. We report that missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells. As a consequence of reduced shedding, TREM2 is virtually absent in the cerebrospinal fluid (CSF) and plasma of a patient with FTD-like syndrome. A decrease in soluble TREM2 was also observed in the CSF of patients with AD and FTD, further suggesting that reduced TREM2 function may contribute to increased risk for two neurodegenerative disorders.
    Science translational medicine 07/2014; 6(243). DOI:10.1126/scitranslmed.3009093 · 14.41 Impact Factor
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    ABSTRACT: BACKGROUND: Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. METHODS: We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10(-8)) single-nucleotide polymorphisms. FINDINGS: We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10(-8)). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, HLA locus (immune system), for rs9268877 (p=1·05 × 10(-8); odds ratio=1·204 [95% CI 1·11-1·30]), rs9268856 (p=5·51 × 10(-9); 0·809 [0·76-0·86]) and rs1980493 (p value=1·57 × 10(-8), 0·775 [0·69-0·86]) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural FTD subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10(-7); 0·814 [0·71-0·92]). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. INTERPRETATION: Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD
    The Lancet Neurology 07/2014; 3(7):686-99. DOI:10.1016/S1474-4422(14)70065-1 · 21.82 Impact Factor
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    ABSTRACT: Clinical and neuropathological similarities between Dementia with Lewy Bodies (DLB), ParkinsonÕs and AlzheimerÕs diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). Results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared to the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available.
    Human Molecular Genetics 06/2014; 23(23). DOI:10.1093/hmg/ddu334 · 6.68 Impact Factor
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    ABSTRACT: The overlapping clinical and neuropathologic features between late-onset apparently sporadic Alzheimer's disease (LOAD), familial Alzheimer's disease, and other neurodegenerative dementias (frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, and Creutzfeldt-Jakob disease) raises the question of whether shared genetic risk factors may explain the similar phenotype among these disparate disorders. To investigate this intriguing hypothesis, we analyzed rare coding variability in 6 Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP), in 141 LOAD patients and 179 elderly controls, neuropathologically proven, from the UK. In our cohort, 14 LOAD cases (10%) and 11 controls (6%) carry at least 1 rare variant in the genes studied. We report a novel variant in PSEN1 (p.I168T) and a rare variant in PSEN2 (p.A237V), absent in controls and both likely pathogenic. Our findings support previous studies, suggesting that (1) rare coding variability in PSEN1 and PSEN2 may influence the susceptibility for LOAD and (2) GRN, MAPT, and PRNP are not major contributors to LOAD. Thus, genetic screening is pivotal for the clinical differential diagnosis of these neurodegenerative dementias.
    Neurobiology of Aging 06/2014; 35(12). DOI:10.1016/j.neurobiolaging.2014.06.002 · 4.85 Impact Factor
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    ABSTRACT: Background: Alzheimer’s disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer’s Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer’s cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p=1.461026) and 14 (IGHV1-67 p=7.961028) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer’s disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer’s disease
    PLoS ONE 06/2014; 9(6):e94661. DOI:10.1371/journal.pone.0094661. · 3.53 Impact Factor
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    ABSTRACT: Progressive supranuclear palsy is a rare parkinsonian disorder with characteristic neurofibrillary pathology consisting of hyperphosphorylated tau protein. Common variation defining the microtubule associated protein tau gene (MAPT) H1 haplotype strongly contributes to disease risk. A recent genome-wide association study (GWAS) revealed 3 novel risk loci on chromosomes 1, 2, and 3 that primarily implicate STX6, EIF2AK3, and MOBP, respectively. Genetic associations, however, rarely lead to direct identification of the relevant functional allele. More often, they are in linkage disequilibrium with the causative polymorphism(s) that could be a coding change or affect gene expression regulatory motifs. To identify any such changes, we sequenced all coding exons of those genes directly implicated by the associations in progressive supranuclear palsy cases and analyzed regional gene expression data from control brains to identify expression quantitative trait loci within 1 Mb of the risk loci. Although we did not find any coding variants underlying the associations, GWAS-associated single-nucleotide polymorphisms at these loci are in complete linkage disequilibrium with haplotypes that completely overlap with the respective genes. Although implication of EIF2AK3 and MOBP could not be fully assessed, we show that the GWAS single-nucleotide polymorphism rs1411478 (STX6) is a strong expression quantitative trait locus with significantly lower expression of STX6 in white matter in carriers of the risk allele.
    Neurobiology of Aging 06/2014; 35(6):1514.e1–1514.e12. DOI:10.1016/j.neurobiolaging.2014.01.010 · 4.85 Impact Factor
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    ABSTRACT: Here, we describe a nonsense haplotype in PRNP associated with clinical Alzheimer's disease. The patient presented an early-onset of cognitive decline with memory loss as the primary cognitive problem. Whole-exome sequencing revealed a nonsense mutation in PRNP (NM_000311, c.C478T; p.Q160*; rs80356711) associated with homozygosity for the V allele at position 129 of the protein, further highlighting how very similar genotypes in PRNP result in strikingly different phenotypes.
    Neurobiology of Aging 05/2014; 35(11). DOI:10.1016/j.neurobiolaging.2014.05.013 · 4.85 Impact Factor
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    ABSTRACT: IMPORTANCE The core clinical and neuropathological feature of the autosomal dominant spinocerebellar ataxias (SCAs) is cerebellar degeneration. Mutations in the known genes explain only 50% to 60% of SCA cases. To date, no effective treatments exist, and the knowledge of drug-treatable molecular pathways is limited. The examination of overlapping mechanisms and the interpretation of how ataxia genes interact will be important in the discovery of potential disease-modifying agents. OBJECTIVES To address the possible relationships among known SCA genes, predict their functions, identify overlapping pathways, and provide a framework for candidate gene discovery using whole-transcriptome expression data. DESIGN, SETTING, AND PARTICIPANTS We have used a systems biology approach based on whole-transcriptome gene expression analysis. As part of the United Kingdom Brain Expression Consortium, we analyzed the expression profile of 788 brain samples obtained from 101 neuropathologically healthy individuals (10 distinct brain regions each). Weighted gene coexpression network analysis was used to cluster 24 SCA genes into gene coexpression modules in an unsupervised manner. The overrepresentation of SCA transcripts in modules identified in the cerebellum was assessed. Enrichment analysis was performed to infer the functions and molecular pathways of genes in biologically relevant modules. MAIN OUTCOMES AND MEASURES Molecular functions and mechanisms implicating SCA genes, as well as lists of relevant coexpressed genes as potential candidates for novel SCA causative or modifier genes. RESULTS Two cerebellar gene coexpression modules were statistically enriched in SCA transcripts (P = .021 for the tan module and P = 2.87 × 10-5 for the light yellow module) and contained established granule and Purkinje cell markers, respectively. One module includes genes involved in the ubiquitin-proteasome system and contains SCA genes usually associated with a complex phenotype, while the other module encloses many genes important for calcium homeostasis and signaling and contains SCA genes associated mostly with pure ataxia. CONCLUSIONS AND RELEVANCE Using normal gene expression in the human brain, we identified significant cell types and pathways in SCA pathogenesis. The overrepresentation of genes involved in calcium homeostasis and signaling may indicate an important target for therapy in the future. Furthermore, the gene networks provide new candidate genes for ataxias or novel genes that may be critical for cerebellar function.
    JAMA Neurology 05/2014; 71(7). DOI:10.1001/jamaneurol.2014.756 · 7.01 Impact Factor
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    ABSTRACT: To identify the genetic cause of a complex syndrome characterized by autophagic vacuolar myopathy (AVM), hypertrophic cardiomyopathy, pigmentary retinal degeneration, and epilepsy.METHODS: Clinical, pathologic, and genetic study.RESULTS: Two brothers presented with visual failure, seizures, and prominent cardiac involvement, but only mild cognitive impairment and no motor deterioration after 40 years of disease duration. Muscle biopsy revealed the presence of widespread alterations suggestive of AVM with autophagic vacuoles with sarcolemmal features. Through combined homozygosity mapping and exome sequencing, we identified a novel p.Gly165Glu mutation in CLN3.CONCLUSIONS: This study expands the clinical phenotype of CLN3 disease. Genetic testing for CLN3 should be considered in AVM with autophagic vacuoles with sarcolemmal features.
    Neurology 05/2014; 82(23). DOI:10.1212/WNL.0000000000000490 · 8.30 Impact Factor
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    ABSTRACT: The development of next-generation sequencing technologies has allowed for the identification of several new genes and genetic factors in Human Genetics. Common results from the application of these technologies have revealed unexpected presentations for mutations in known disease genes. In this review we summarise the major contributions of exome sequencing to the study of neurodegenerative disorders and other neurological conditions and discuss the interface between Mendelian and complex neurological diseases with a particular focus on pleiotropic events.
    Human Molecular Genetics 05/2014; 23(R1). DOI:10.1093/hmg/ddu203 · 6.68 Impact Factor
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    ABSTRACT: Background: Haplotype structure of the microtubule-associated protein tau (MAPT) gene is associated with various tauopathies in the Caucasian population. With the knowledge that the association between MAPT structure and disease may be distinct in different ethnics, we intend to investigate the haplotype structure of MAPT in Taiwanese and test it for association with Alzheimer's disease (AD). Methods: One hundred and eight AD patients and 108 sex- and-age matched healthy controls were recruited from the dementia outpatient clinic of Chang Gung Medical center. We genotyped the del-In9 marker that defines the extended H1 and H2 clades. We selected 21 single-nucleotide polymorphisms (SNPs) in the extended MAPT region from Japanese SNPs database and dbSNP database. Using the software TagIt, we analyzed the linkage disequilibrium structure of MAPT and compared the allele and genotype distribution between patient group and control group. Results: All the Taiwanese participants were H1 haplotypes. Linkage disequilibrium analysis showed the haplotype blocks in Taiwanese population had a smaller size in comparison to that of the Caucasian population. Single locus association showed significant p value in one of the tagging variants (rs242557) in our Taiwanese AD case-control cohorts. Conclusion: MAPT gene has four haplotype blocks in the Taiwanese population, each of around 40 kbp. In both European study and our study, the SNP rs242557 showed association with AD. Given the position of this SNP, the most possible explanation is that genetic variability in tau expression contributes to the risk of developing AD.
    05/2014; 37(3):127-32. DOI:10.4103/2319-4170.117891
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    Jin-Tai Yu, Lan Tan, John Hardy
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    ABSTRACT: The vast majority of Alzheimer's disease (AD) cases are late onset (LOAD), which is genetically complex with heritability estimates up to 80%. Apolipoprotein E (APOE) has been irrefutably recognized as the major genetic risk factor, with semidominant inheritance, for LOAD. Although the mechanisms that underlie the pathogenic nature of APOE in AD are still not completely understood, emerging data suggest that APOE contributes to AD pathogenesis through both amyloid-β (Aβ)-dependent and Aβ-independent pathways. Given the central role for APOE in the modulation of AD pathogenesis, many therapeutic strategies have emerged, including converting APOE conformation, regulating APOE expression, mimicking APOE peptides, blocking the APOE/Aβ interaction, modulating APOE lipidation state, and gene therapy. Accumulating evidence also suggests the utility of APOE genotyping in AD diagnosis, risk assessment, prevention, and treatment response. Expected final online publication date for the Annual Review of Neuroscience Volume 37 is July 08, 2014. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
    Annual Review of Neuroscience 04/2014; DOI:10.1146/annurev-neuro-071013-014300 · 22.66 Impact Factor

Publication Stats

61k Citations
7,226.10 Total Impact Points

Institutions

  • 2007–2015
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
    • University of Miami
      كورال غيبلز، فلوريدا, Florida, United States
    • Duke University
      Durham, North Carolina, United States
    • Translational Genomics Research Institute
      • Division of Neurogenomics
      Phoenix, AZ, United States
  • 2001–2015
    • University College London
      • • Department of Molecular Neuroscience
      • • Institute of Neurology
      Londinium, England, United Kingdom
  • 2012–2014
    • WWF United Kingdom
      Londinium, England, United Kingdom
    • University of Thessaly
      • Κλινική Νευρολογίας
      Iolcus, Thessaly, Greece
    • Banner Alzheimer's Institute
      Phoenix, Arizona, United States
  • 2013
    • L'Institut du Cerveau et de la Moelle Épinière
      Lutetia Parisorum, Île-de-France, France
    • University of Campinas
      Conceição de Campinas, São Paulo, Brazil
  • 2011–2012
    • Cardiff University
      • • School of Medicine
      • • Department of Psychological Medicine and Neurology
      Cardiff, Wales, United Kingdom
  • 2002–2012
    • National Institute on Aging
      • Laboratory of Neurogenetics (LNG)
      Baltimore, Maryland, United States
    • Tehran University of Medical Sciences
      • Department of Biochemistry
      Tehrān, Ostan-e Tehran, Iran
    • Mayo Clinic - Rochester
      • Department of Neurology
      Рочестер, Minnesota, United States
    • Institut Pasteur de Lille
      Lille, Nord-Pas-de-Calais, France
  • 2010
    • University of Geneva
      • Department of Genetic Medicine and Development (GEDEV)
      Genève, GE, Switzerland
  • 2002–2009
    • National Institutes of Health
      • Laboratory of Neurogenetics
      Maryland, United States
  • 1992–2009
    • University of South Florida
      Tampa, Florida, United States
  • 1991–2009
    • Imperial College London
      Londinium, England, United Kingdom
    • Yale University
      New Haven, Connecticut, United States
    • Florida Clinical Research Center
      Florida, United States
  • 2008
    • London Research Institute
      Londinium, England, United Kingdom
    • University of Miami Miller School of Medicine
      • Department of Psychiatry and Behavioral Sciences
      Miami, Florida, United States
  • 1999–2008
    • University of Helsinki
      • • Department of Pathology
      • • Department of Neurology
      Helsinki, Uusimaa, Finland
    • University of California, Los Angeles
      Los Ángeles, California, United States
    • Mater Misericordiae University Hospital
      Dublin, Leinster, Ireland
  • 2006
    • University of Toronto
      Toronto, Ontario, Canada
    • University of Sydney
      Sydney, New South Wales, Australia
  • 2005
    • Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2004
    • William Penn University
      Filadelfia, Pennsylvania, United States
    • Chang Gung University
      Hsin-chu-hsien, Taiwan, Taiwan
    • Northern Inyo Hospital
      BIH, California, United States
    • Hospital Universitario Fundacion Alcorcon
      Madrid, Madrid, Spain
  • 2003
    • Medical University of South Carolina
      Charleston, South Carolina, United States
  • 1997–2003
    • Mayo Foundation for Medical Education and Research
      • • Department of Neurology
      • • Department of Pharmacology
      Scottsdale, AZ, United States
    • Jacksonville College
      Jacksonville, Florida, United States
  • 2000–2001
    • Ludwig-Maximilian-University of Munich
      • Department of Biochemistry
      München, Bavaria, Germany
  • 1998
    • Central Institute of Mental Health
      Mannheim, Baden-Württemberg, Germany
    • Columbia University
      • Department of Neurology
      New York City, New York, United States
  • 1995–1998
    • Washington University in St. Louis
      • Department of Psychiatry
      Saint Louis, MO, United States
  • 1996
    • Washington School of Psychiatry
      Washington, Washington, D.C., United States
  • 1994
    • University of Essex
      Colchester, England, United Kingdom
  • 1989–1993
    • Imperial College Healthcare NHS Trust
      • Division of Biochemistry
      Londinium, England, United Kingdom