Research Theme Beyond the Neuron

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Professor Patrick Chinnery FRCP FMedSci

University Position

Head of Department

Interests

I am interested in the genetic basis of neurological disorders, and particularly mitochondrial diseases. Mitochondria are the main source of energy within neurons and glia. Mutations in genes responsible for mitochondrial biogenesis are a major cause of human disease, affecting multiple organs including the brain. My laboratory research programme is based in the MRC Mitochondrial Biology Unit, and studies the mechanisms of mitochondrial disease in patients and model systems. Our aim is to understand why specific cell types are so vulnerable in mitochondrial diseases. I have an active genomics programme identifying new disease genes and mechanisms in neurological disorders. I also have an active clinical research programme developing new treatments for mitochondrial disorders.

Associated News Items

Key Publications

Mitochondrial DNA disorders in neuromuscular diseases in diverse populations

DOI: http://doi.org/10.1002/acn3.52141
Journal: Ann Clin Transl Neurol
E-pub date: 2 Aug 2024
Authors: F Gao, KR Schon, J Vandrovcova, L Wilson, MG Hanna, B Çavdarlı, J Heckmann, PF Chinnery, R Horvath

Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes.

DOI: http://doi.org/10.1038/s41586-022-05288-7
Journal: Nature
E-pub date: 1 Nov 2022
Authors: W Wei, KR Schon, G Elgar, A Orioli, M Tanguy, A Giess, M Tischkowitz, MJ Caulfield, PF Chinnery

Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study.

DOI: http://doi.org/10.1136/bmj-2021-066288
Journal: BMJ
E-pub date: 3 Nov 2021
Authors: KR Schon, R Horvath, W Wei, C Calabrese, A Tucci, K Ibañez, T Ratnaike, RDS Pitceathly, E Bugiardini, R Quinlivan, MG Hanna, E Clement, E Ashton, JA Sayer, P Brennan, D Josifova, L Izatt, C Fratter, V Nesbitt, T Barrett, DJ McMullen, A Smith, C Deshpande, SF Smithson, R Festenstein, N Canham, M Caulfield, H Houlden, S Rahman, PF Chinnery, Genomics England Research Consortium

Mitochondrial Diseases: A Diagnostic Revolution.

DOI: http://doi.org/10.1016/j.tig.2020.06.009
Journal: Trends Genet
E-pub date: 1 Sep 2020
Authors: KR Schon, T Ratnaike, J van den Ameele, R Horvath, PF Chinnery

Tau and alpha-synuclein in susceptibility to, and dementia in, Parkinson’s disease.

DOI: http://doi.org/10.1002/ana.21192
Journal: Ann Neurol
E-pub date: 31 Aug 2007
Authors: A Goris, CH Williams-Gray, GR Clark, T Foltynie, SJG Lewis, J Brown, M Ban, MG Spillantini, A Compston, DJ Burn, PF Chinnery, RA Barker, SJ Sawcer

Publications

Evidence for sodium valproate toxicity in mitochondrial diseases: a systematic analysis

DOI: http://doi.org/10.1136/bmjno-2024-000650
Journal: BMJ Neurol Open
E-pub date: 1 Aug 2024
Authors: TE Ratnaike, N Elkhateeb, A Lochmüller, C Gilmartin, K Schon, R Horváth, PF Chinnery

Neuromuscular disease genetics in underrepresented populations: increasing data diversity.

DOI: http://doi.org/10.1093/brain/awad254
Journal: Brain
E-pub date: 1 Dec 2023
Authors: LA Wilson, WL Macken, LD Perry, CJ Record, KR Schon, RSS Frezatti, S Raga, K Naidu, ÖY Köken, I Polat, MM Kapapa, N Dominik, S Efthymiou, H Morsy, M Nel, MR Fassad, F Gao, K Patel, M Schoonen, M Bisschoff, A Vorster, H Jonvik, R Human, E Lubbe, M Nonyane, S Vengalil, S Nashi, K Srivastava, RJLF Lemmers, A Reyaz, R Mishra, A Töpf, CI Trainor, EC Steyn, AC Mahungu, PJ van der Vliet, AC Ceylan, AS Hiz, B Çavdarlı, CN Semerci Gündüz, GG Ceylan, M Nagappa, KB Tallapaka, P Govindaraj, SM van der Maarel, G Narayanappa, BN Nandeesh, S Wa Somwe, DR Bearden, MP Kvalsund, GM Ramdharry, Y Oktay, U Yiş, H Topaloğlu, A Sarkozy, E Bugiardini, F Henning, JM Wilmshurst, JM Heckmann, R McFarland, RW Taylor, I Smuts, FH van der Westhuizen, CFDR Sobreira, PJ Tomaselli, W Marques, R Bhatia, A Dalal, MVP Srivastava, S Yareeda, A Nalini, VY Vishnu, K Thangaraj, V Straub, R Horvath, PF Chinnery, RDS Pitceathly, F Muntoni, H Houlden, J Vandrovcova, MM Reilly, MG Hanna

High-Depth PRNP Sequencing in Brains With Sporadic Creutzfeldt-Jakob Disease.

DOI: http://doi.org/10.1212/NXG.0000000000200054
Journal: Neurol Genet
E-pub date: 1 Feb 2023
Authors: AG Murley, Y Nie, Z Golder, MJ Keogh, C Smith, JW Ironside, PF Chinnery

Whole-genome sequencing for mitochondrial disorders identifies unexpected mimics.

DOI: http://doi.org/10.1136/pn-2022-003570
Journal: Pract Neurol
E-pub date: 1 Feb 2023
Authors: KR Schon, PF Chinnery

Heteroplasmic mitochondrial DNA mutations in frontotemporal lobar degeneration.

DOI: http://doi.org/10.1007/s00401-022-02423-6
Journal: Acta Neuropathol
E-pub date: 1 Jun 2022
Authors: Y Nie, A Murley, Z Golder, JB Rowe, K Allinson, PF Chinnery

High diagnostic rate of trio exome sequencing in consanguineous families with neurogenetic diseases.

DOI: http://doi.org/10.1093/brain/awab395
Journal: Brain
E-pub date: 24 May 2022
Authors: S Hiz Kurul, Y Oktay, A Töpf, NZ Szabó, S Güngör, A Yaramis, E Sonmezler, L Matalonga, U Yis, K Schon, I Paramonov, İP Kalafatcilar, F Gao, A Rieger, N Arslan, E Yilmaz, B Ekinci, PP Edem, M Aslan, B Özgör, A Lochmüller, A Nair, E O'Heir, AK Lovgren, Broad Center for Mendelian Genomics, R Maroofian, H Houlden, K Polavarapu, A Roos, JS Müller, D Hathazi, PF Chinnery, S Laurie, S Beltran, H Lochmüller, R Horvath

MitoPhen database: a human phenotype ontology-based approach to identify mitochondrial DNA diseases.

DOI: http://doi.org/10.1093/nar/gkab726
Journal: Nucleic Acids Res
E-pub date: 27 Sep 2021
Authors: TE Ratnaike, D Greene, W Wei, A Sanchis-Juan, KR Schon, J van den Ameele, L Raymond, R Horvath, E Turro, PF Chinnery

Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases.

DOI: http://doi.org/10.1038/s41591-021-01441-3
Journal: Nat Med
E-pub date: 1 Sep 2021
Authors: N Cai, A Gomez-Duran, E Yonova-Doing, K Kundu, AI Burgess, ZJ Golder, C Calabrese, MJ Bonder, M Camacho, RA Lawson, L Li, CH Williams-Gray, ICICLE-PD Study Group, E Di Angelantonio, DJ Roberts, NA Watkins, WH Ouwehand, AS Butterworth, ID Stewart, M Pietzner, NJ Wareham, C Langenberg, J Danesh, K Walter, PM Rothwell, JMM Howson, O Stegle, PF Chinnery, N Soranzo

Exome reanalysis and proteomic profiling identified TRIP4 as a novel cause of cerebellar hypoplasia and spinal muscular atrophy (PCH1).

DOI: http://doi.org/10.1038/s41431-021-00851-8
Journal: Eur J Hum Genet
E-pub date: 1 Sep 2021
Authors: A Töpf, A Pyle, H Griffin, L Matalonga, K Schon, Solve-RD SNV-indel working group, Solve-RD DITF-euroNMD, A Sickmann, U Schara-Schmidt, A Hentschel, PF Chinnery, H Kölbel, A Roos, R Horvath

An atlas of mitochondrial DNA genotype-phenotype associations in the UK Biobank.

DOI: http://doi.org/10.1038/s41588-021-00868-1
Journal: Nat Genet
E-pub date: 1 Jul 2021
Authors: E Yonova-Doing, C Calabrese, A Gomez-Duran, K Schon, W Wei, S Karthikeyan, PF Chinnery, JMM Howson

[11C]PK11195-PET Brain Imaging of the Mitochondrial Translocator Protein in Mitochondrial Disease.

DOI: http://doi.org/10.1212/WNL.0000000000012033
Journal: Neurology
E-pub date: 31 May 2021
Authors: J van den Ameele, Y Hong, R Manavaki, A Kouli, H Biggs, Z MacIntyre, R Horvath, P Yu-Wai-Man, E Reid, CH Williams-Gray, E Bullmore, F Aigbirhio, T Fryer, P Chinnery

Epigenetic regulation in the pathophysiology of Lewy body dementia.

DOI: http://doi.org/10.1016/j.pneurobio.2020.101822
Journal: Prog Neurobiol
E-pub date: 1 Sep 2020
Authors: L Chouliaras, GS Kumar, AJ Thomas, K Lunnon, PF Chinnery, JT O'Brien

A guide to writing systematic reviews of rare disease treatments to generate FAIR-compliant datasets: building a Treatabolome.

DOI: http://doi.org/10.1186/s13023-020-01493-7
Journal: Orphanet J Rare Dis
E-pub date: 12 Aug 2020
Authors: A Atalaia, R Thompson, A Corvo, L Carmody, D Piscia, L Matalonga, A Macaya, A Lochmuller, B Fontaine, B Zurek, C Hernandez-Ferrer, C Reinhard, D Gómez-Andrés, J-F Desaphy, K Schon, K Lohmann, MJ Jennings, M Synofzik, O Riess, RB Yaou, T Evangelista, T Ratnaike, V Bros-Facer, G Gumus, R Horvath, P Chinnery, S Laurie, H Graessner, P Robinson, H Lochmuller, S Beltran, G Bonne

Chronic pain is common in mitochondrial disease.

DOI: http://doi.org/10.1016/j.nmd.2020.02.017
Journal: Neuromuscul Disord
E-pub date: 1 May 2020
Authors: J van den Ameele, J Fuge, RDS Pitceathly, S Berry, Z McIntyre, MG Hanna, M Lee, PF Chinnery

Mitochondrial heteroplasmy beyond the oocyte bottleneck.

DOI: http://doi.org/10.1016/j.semcdb.2019.10.001
Journal: Semin Cell Dev Biol
E-pub date: 1 Jan 2020
Authors: J van den Ameele, AYZ Li, H Ma, PF Chinnery

High prevalence of focal and multi-focal somatic genetic variants in the human brain.

DOI: http://doi.org/10.1038/s41467-018-06331-w
Journal: Nat Commun
E-pub date: 15 Oct 2018
Authors: MJ Keogh, W Wei, J Aryaman, L Walker, J van den Ameele, J Coxhead, I Wilson, M Bashton, J Beck, J West, R Chen, C Haudenschild, G Bartha, S Luo, CM Morris, NS Jones, J Attems, PF Chinnery

Stability of mild cognitive impairment in newly diagnosed Parkinson’s disease.

DOI: http://doi.org/10.1136/jnnp-2016-315099
Journal: J Neurol Neurosurg Psychiatry
E-pub date: 31 Aug 2017
Authors: RA Lawson, AJ Yarnall, GW Duncan, DP Breen, TK Khoo, CH Williams-Gray, RA Barker, DJ Burn, ICICLE-PD study group

Discovery and functional prioritization of Parkinson’s disease candidate genes from large-scale whole exome sequencing.

DOI: http://doi.org/10.1186/s13059-017-1147-9
Journal: Genome Biol
E-pub date: 30 Jan 2017
Authors: IE Jansen, H Ye, S Heetveld, MC Lechler, H Michels, RI Seinstra, SJ Lubbe, V Drouet, S Lesage, E Majounie, JR Gibbs, MA Nalls, M Ryten, JA Botia, J Vandrovcova, J Simon-Sanchez, M Castillo-Lizardo, P Rizzu, C Blauwendraat, AK Chouhan, Y Li, P Yogi, N Amin, CM van Duijn, International Parkinson’s Disease Genetics Consortium (IPGDC), HR Morris, A Brice, AB Singleton, DC David, EA Nollen, S Jain, JM Shulman, P Heutink

Exome sequencing in dementia with Lewy bodies.

DOI: http://doi.org/10.1038/tp.2015.220
Journal: Transl Psychiatry
E-pub date: 2 Feb 2016
Authors: MJ Keogh, M Kurzawa-Akanbi, H Griffin, K Douroudis, KL Ayers, RI Hussein, G Hudson, A Pyle, HJ Cordell, J Attems, IG McKeith, JT O'Brien, DJ Burn, CM Morris, AJ Thomas, PF Chinnery

NeuroX, a fast and efficient genotyping platform for investigation of neurodegenerative diseases.

DOI: http://doi.org/10.1016/j.neurobiolaging.2014.07.028
Journal: Neurobiol Aging
E-pub date: 1 Mar 2015
Authors: MA Nalls, J Bras, DG Hernandez, MF Keller, E Majounie, AE Renton, M Saad, I Jansen, R Guerreiro, S Lubbe, V Plagnol, JR Gibbs, C Schulte, N Pankratz, M Sutherland, L Bertram, CM Lill, AL DeStefano, T Faroud, N Eriksson, JY Tung, C Edsall, N Nichols, J Brooks, S Arepalli, H Pliner, C Letson, P Heutink, M Martinez, T Gasser, BJ Traynor, N Wood, J Hardy, AB Singleton, International Parkinson's Disease Genomics Consortium (IPDGC), Parkinson's Disease meta-analysis consortium

Genetic comorbidities in Parkinson’s disease.

DOI: http://doi.org/10.1093/hmg/ddt465
Journal: Hum Mol Genet
E-pub date: 1 Feb 2014
Authors: MA Nalls, M Saad, AJ Noyce, MF Keller, A Schrag, JP Bestwick, BJ Traynor, JR Gibbs, DG Hernandez, MR Cookson, HR Morris, N Williams, T Gasser, P Heutink, N Wood, J Hardy, M Martinez, AB Singleton, International Parkinson's Disease Genomics Consortium (IPDGC), Wellcome Trust Case Control Consortium 2 (WTCCC2), North American Brain Expression Consortium (NABEC), United Kingdom Brain Expression Consortium (UKBEC)

Serum iron levels and the risk of Parkinson disease: a Mendelian randomization study.

DOI: http://doi.org/10.1371/journal.pmed.1001462
Journal: PLoS Med
E-pub date: 1 Aug 2013
Authors: I Pichler, F Del Greco M, M Gögele, CM Lill, L Bertram, CB Do, N Eriksson, T Foroud, RH Myers, PD GWAS Consortium, M Nalls, MF Keller, International Parkinson's Disease Genomics Consortium, Wellcome Trust Case Control Consortium 2, B Benyamin, JB Whitfield, Genetics of Iron Status Consortium, PP Pramstaller, AA Hicks, JR Thompson, C Minelli

The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson’s disease with a sexual dimorphism.

DOI: http://doi.org/10.1136/jnnp-2012-304475
Journal: J Neurol Neurosurg Psychiatry
E-pub date: 1 Jun 2013
Authors: S Klebe, J-L Golmard, MA Nalls, M Saad, AB Singleton, JM Bras, J Hardy, J Simon-Sanchez, P Heutink, G Kuhlenbäumer, R Charfi, C Klein, J Hagenah, T Gasser, I Wurster, S Lesage, D Lorenz, G Deuschl, F Durif, P Pollak, P Damier, F Tison, A Durr, P Amouyel, J-C Lambert, C Tzourio, C Maubaret, F Charbonnier-Beaupel, K Tahiri, M Vidailhet, M Martinez, A Brice, J-C Corvol, French Parkinson's Disease Genetics Study Group, International Parkinson's Disease Genomics Consortium (IPDGC)

Two-stage association study and meta-analysis of mitochondrial DNA variants in Parkinson disease.

DOI: http://doi.org/10.1212/WNL.0b013e318294b434
Journal: Neurology
E-pub date: 28 May 2013
Authors: G Hudson, M Nalls, JR Evans, DP Breen, S Winder-Rhodes, KE Morrison, HR Morris, CH Williams-Gray, RA Barker, AB Singleton, J Hardy, NE Wood, DJ Burn, PF Chinnery

A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson’s disease.

DOI: http://doi.org/10.1093/hmg/dds492
Journal: Hum Mol Genet
E-pub date: 1 Mar 2013
Authors: P Holmans, V Moskvina, L Jones, M Sharma, International Parkinson's Disease Genomics Consortium, A Vedernikov, F Buchel, M Saad, JM Bras, F Bettella, N Nicolaou, J Simón-Sánchez, F Mittag, JR Gibbs, C Schulte, A Durr, R Guerreiro, D Hernandez, A Brice, H Stefánsson, K Majamaa, T Gasser, P Heutink, NW Wood, M Martinez, AB Singleton, MA Nalls, J Hardy, HR Morris, NM Williams

Use of support vector machines for disease risk prediction in genome-wide association studies: concerns and opportunities.

DOI: http://doi.org/10.1002/humu.22161
Journal: Hum Mutat
E-pub date: 1 Dec 2012
Authors: F Mittag, F Büchel, M Saad, A Jahn, C Schulte, Z Bochdanovits, J Simón-Sánchez, MA Nalls, M Keller, DG Hernandez, JR Gibbs, S Lesage, A Brice, P Heutink, M Martinez, NW Wood, J Hardy, AB Singleton, A Zell, T Gasser, M Sharma, International Parkinson’s Disease Genomics Consortium

Using genome-wide complex trait analysis to quantify ‘missing heritability’ in Parkinson’s disease.

DOI: http://doi.org/10.1093/hmg/dds335
Journal: Hum Mol Genet
E-pub date: 15 Nov 2012
Authors: MF Keller, M Saad, J Bras, F Bettella, N Nicolaou, J Simón-Sánchez, F Mittag, F Büchel, M Sharma, JR Gibbs, C Schulte, V Moskvina, A Durr, P Holmans, LL Kilarski, R Guerreiro, DG Hernandez, A Brice, P Ylikotila, H Stefánsson, K Majamaa, HR Morris, N Williams, T Gasser, P Heutink, NW Wood, J Hardy, M Martinez, AB Singleton, MA Nalls, International Parkinson's Disease Genomics Consortium (IPDGC), Wellcome Trust Case Control Consortium 2 (WTCCC2)

Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson’s disease.

DOI: http://doi.org/10.1002/mds.25132
Journal: Mov Disord
E-pub date: 1 Oct 2012
Authors: LL Kilarski, JP Pearson, V Newsway, E Majounie, MDW Knipe, A Misbahuddin, PF Chinnery, DJ Burn, CE Clarke, M-H Marion, AJ Lewthwaite, DJ Nicholl, NW Wood, KE Morrison, CH Williams-Gray, JR Evans, SJ Sawcer, RA Barker, MM Wickremaratchi, Y Ben-Shlomo, NM Williams, HR Morris

Genetic and pathological links between Parkinson’s disease and the lysosomal disorder Sanfilippo syndrome.

DOI: http://doi.org/10.1002/mds.24029
Journal: Mov Disord
E-pub date: 1 Feb 2012
Authors: SE Winder-Rhodes, P Garcia-Reitböck, M Ban, JR Evans, TS Jacques, A Kemppinen, T Foltynie, CH Williams-Gray, PF Chinnery, G Hudson, DJ Burn, LM Allcock, SJ Sawcer, RA Barker, MG Spillantini

A two-stage meta-analysis identifies several new loci for Parkinson’s disease.

DOI: http://doi.org/10.1371/journal.pgen.1002142
Journal: PLoS Genet
E-pub date: 1 Jun 2011
Authors: International Parkinson's Disease Genomics Consortium (IPDGC), Wellcome Trust Case Control Consortium 2 (WTCCC2)

Imputation of sequence variants for identification of genetic risks for Parkinson’s disease: a meta-analysis of genome-wide association studies.

DOI: http://doi.org/10.1016/S0140-6736(10)62345-8
Journal: Lancet
E-pub date: 19 Feb 2011
Authors: International Parkinson Disease Genomics Consortium, MA Nalls, V Plagnol, DG Hernandez, M Sharma, U-M Sheerin, M Saad, J Simón-Sánchez, C Schulte, S Lesage, S Sveinbjörnsdóttir, K Stefánsson, M Martinez, J Hardy, P Heutink, A Brice, T Gasser, AB Singleton, NW Wood

The mitochondrial DNA A3243A>G mutation must be an infrequent cause of Asperger syndrome.

DOI: http://doi.org/10.1016/j.jpeds.2005.08.060
Journal: J Pediatr
E-pub date: 31 Aug 2006
Authors: L Kent, C Lambert, A Pyle, H Elliott, S Wheelwright, S Baron-Cohen, PF Chinnery