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Pathological relationships involving iron and myelin may constitute a shared mechanism linking various rare and common brain diseases.

Rare diseases (Austin, Tex.)

Heidari M, Gerami SH, Bassett B, Graham RM, Chua AC, Aryal R, House MJ, Collingwood JF, Bettencourt C, Houlden H, Ryten M, Olynyk JK, Trinder D, Johnstone DM, Milward EA.
PMID: 27500074
Rare Dis. 2016 Jun 22;4(1):e1198458. doi: 10.1080/21675511.2016.1198458. eCollection 2016.

We previously demonstrated elevated brain iron levels in myelinated structures and associated cells in a hemochromatosis Hfe (-/-) xTfr2 (mut) mouse model. This was accompanied by altered expression of a group of myelin-related genes, including a suite of genes...

Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases.

Annals of clinical and translational neurology

Gagliano SA, Pouget JG, Hardy J, Knight J, Barnes MR, Ryten M, Weale ME.
PMID: 28097204
Ann Clin Transl Neurol. 2016 Nov 04;3(12):924-933. doi: 10.1002/acn3.369. eCollection 2016 Dec.

OBJECTIVES: We assessed the current genetic evidence for the involvement of various cell types and tissue types in the etiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases.METHODS: We obtained large-scale genome-wide association study...

Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson's disease heritability.

NPJ Parkinson's disease

Reynolds RH, Botía J, Nalls MA, Hardy J, Gagliano Taliun SA, Ryten M.
PMID: 31016231
NPJ Parkinsons Dis. 2019 Apr 17;5:6. doi: 10.1038/s41531-019-0076-6. eCollection 2019.

Parkinson's disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes...

Identification of Candidate Parkinson Disease Genes by Integrating Genome-Wide Association Study, Expression, and Epigenetic Data Sets.

JAMA neurology

Kia DA, Zhang D, Guelfi S, Manzoni C, Hubbard L, Reynolds RH, Botía J, Ryten M, Ferrari R, Lewis PA, Williams N, Trabzuni D, Hardy J, Wood NW.
PMID: 33523105
JAMA Neurol. 2021 Apr 01;78(4):464-472. doi: 10.1001/jamaneurol.2020.5257.

IMPORTANCE: Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and...

Failures in Protein Clearance Partly Underlie Late Onset Neurodegenerative Diseases and Link Pathology to Genetic Risk.

Frontiers in neuroscience

Hardy J.
PMID: 31866813
Front Neurosci. 2019 Dec 05;13:1304. doi: 10.3389/fnins.2019.01304. eCollection 2019.

As we identify the loci involved in late onset neurodegenerative disease, we are finding that the majority of them are involved in damage response processes. In this short review, I propose that it is partly a failure in these...

Identification of Candidate Parkinson Disease Genes by Integrating Genome-Wide Association Study, Expression, and Epigenetic Data Sets.

JAMA neurology

Kia DA, Zhang D, Guelfi S, Manzoni C, Hubbard L, Reynolds RH, Botía J, Ryten M, Ferrari R, Lewis PA, Williams N, Trabzuni D, Hardy J, Wood NW.
PMID: 33523105
JAMA Neurol. 2021 Apr 01;78(4):464-472. doi: 10.1001/jamaneurol.2020.5257.

IMPORTANCE: Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and...

Author Correction: Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

Nature genetics

Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, Boland A, Vronskaya M, van der Lee SJ, Amlie-Wolf A, Bellenguez C, Frizatti A, Chouraki V, Martin ER, Sleegers K, Badarinarayan N, Jakobsdottir J, Hamilton-Nelson KL, Moreno-Grau S, Olaso R, Raybould R, Chen Y, Kuzma AB, Hiltunen M, Morgan T, Ahmad S, Vardarajan BN, Epelbaum J, Hoffmann P, Boada M, Beecham GW, Garnier JG, Harold D, Fitzpatrick AL, Valladares O, Moutet ML, Gerrish A, Smith AV, Qu L, Bacq D, Denning N, Jian X, Zhao Y, Del Zompo M, Fox NC, Choi SH, Mateo I, Hughes JT, Adams HH, Malamon J, Sanchez-Garcia F, Patel Y, Brody JA, Dombroski BA, Naranjo MCD, Daniilidou M, Eiriksdottir G, Mukherjee S, Wallon D, Uphill J, Aspelund T, Cantwell LB, Garzia F, Galimberti D, Hofer E, Butkiewicz M, Fin B, Scarpini E, Sarnowski C, Bush WS, Meslage S, Kornhuber J, White CC, Song Y, Barber RC, Engelborghs S, Sordon S, Voijnovic D, Adams PM, Vandenberghe R, Mayhaus M, Cupples LA, Albert MS, De Deyn PP, Gu W, Himali JJ, Beekly D, Squassina A, Hartmann AM, Orellana A, Blacker D, Rodriguez-Rodriguez E, Lovestone S, Garcia ME, Doody RS, Munoz-Fernadez C, Sussams R, Lin H, Fairchild TJ, Benito YA, Holmes C, Karamujić-Čomić H, Frosch MP, Thonberg H, Maier W, Roshchupkin G, Ghetti B, Giedraitis V, Kawalia A, Li S, Huebinger RM, Kilander L, Moebus S, Hernández I, Kamboh MI, Brundin R, Turton J, Yang Q, Katz MJ, Concari L, Lord J, Beiser AS, Keene CD, Helisalmi S, Kloszewska I, Kukull WA, Koivisto AM, Lynch A, Tarraga L, Larson EB, Haapasalo A, Lawlor B, Mosley TH, Lipton RB, Solfrizzi V, Gill M, Longstreth WT, Montine TJ, Frisardi V, Diez-Fairen M, Rivadeneira F, Petersen RC, Deramecourt V, Alvarez I, Salani F, Ciaramella A, Boerwinkle E, Reiman EM, Fievet N, Rotter JI, Reisch JS, Hanon O, Cupidi C, Uitterlinden AGA, Royall DR, Dufouil C, Maletta RG, de Rojas I, Sano M, Brice A, Cecchetti R, George-Hyslop PS, Ritchie K, Tsolaki M, Tsuang DW, Dubois B, Craig D, Wu CK, Soininen H, Avramidou D, Albin RL, Fratiglioni L, Germanou A, Apostolova LG, Keller L, Koutroumani M, Arnold SE, Panza F, Gkatzima O, Asthana S, Hannequin D, Whitehead P, Atwood CS, Caffarra P, Hampel H, Quintela I, Carracedo Á, Lannfelt L, Rubinsztein DC, Barnes LL, Pasquier F, Frölich L, Barral S, McGuinness B, Beach TG, Johnston JA, Becker JT, Passmore P, Bigio EH, Schott JM, Bird TD, Warren JD, Boeve BF, Lupton MK, Bowen JD, Proitsi P, Boxer A, Powell JF, Burke JR, Kauwe JSK, Burns JM, Mancuso M, Buxbaum JD, Bonuccelli U, Cairns NJ, McQuillin A, Cao C, Livingston G, Carlson CS, Bass NJ, Carlsson CM, Hardy J, Carney RM, Bras J, Carrasquillo MM, Guerreiro R, Allen M, Chui HC, Fisher E, Masullo C, Crocco EA, DeCarli C, Bisceglio G, Dick M, Ma L, Duara R, Graff-Radford NR, Evans DA, Hodges A, Faber KM, Scherer M, Fallon KB, Riemenschneider M, Fardo DW, Heun R, Farlow MR, Kölsch H, Ferris S, Leber M, Foroud TM, Heuser I, Galasko DR, Giegling I, Gearing M, Hüll M, Geschwind DH, Gilbert JR, Morris J, Green RC, Mayo K, Growdon JH, Feulner T, Hamilton RL, Harrell LE, Drichel D, Honig LS, Cushion TD, Huentelman MJ, Hollingworth P, Hulette CM, Hyman BT, Marshall R, Jarvik GP, Meggy A, Abner E, Menzies GE, Jin LW, Leonenko G, Real LM, Jun GR, Baldwin CT, Grozeva D, Karydas A, Russo G, Kaye JA, Kim R, Jessen F, Kowall NW, Vellas B, Kramer JH, Vardy E, LaFerla FM, Jöckel KH, Lah JJ, Dichgans M, Leverenz JB, Mann D, Levey AI, Pickering-Brown S, Lieberman AP, Klopp N, Lunetta KL, Wichmann HE, Lyketsos CG, Morgan K, Marson DC, Brown K, Martiniuk F, Medway C, Mash DC, Nöthen MM, Masliah E, Hooper NM, McCormick WC, Daniele A, McCurry SM, Bayer A, McDavid AN, Gallacher J, McKee AC, van den Bussche H, Mesulam M, Brayne C, Miller BL, Riedel-Heller S, Miller CA, Miller JW, Al-Chalabi A, Morris JC, Shaw CE, Myers AJ, Wiltfang J, O'Bryant S, Olichney JM, Alvarez V, Parisi JE, Singleton AB, Paulson HL, Collinge J, Perry WR, Mead S, Peskind E, Cribbs DH, Rossor M, Pierce A, Ryan NS, Poon WW, Nacmias B, Potter H, Sorbi S, Quinn JF, Sacchinelli E, Raj A, Spalletta G, Raskind M, Caltagirone C, Bossù P, Orfei MD, Reisberg B, Clarke R, Reitz C, Smith AD, Ringman JM, Warden D, Roberson ED, Wilcock G, Rogaeva E, Bruni AC, Rosen HJ, Gallo M, Rosenberg RN, Ben-Shlomo Y, Sager MA, Mecocci P, Saykin AJ, Pastor P, Cuccaro ML, Vance JM, Schneider JA, Schneider LS, Slifer S, Seeley WW, Smith AG, Sonnen JA, Spina S, Stern RA, Swerdlow RH, Tang M, Tanzi RE, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Van Eldik LJ, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Wilhelmsen KC, Williamson J, Wingo TS, Woltjer RL, Wright CB, Yu CE, Yu L, Saba Y, Pilotto A, Bullido MJ, Peters O, Crane PK, Bennett D, Bosco P, Coto E, Boccardi V, De Jager PL, Lleo A, Warner N, Lopez OL, Ingelsson M, Deloukas P, Cruchaga C, Graff C, Gwilliam R, Fornage M, Goate AM, Sanchez-Juan P, Kehoe PG, Amin N, Ertekin-Taner N, Berr C, Debette S, Love S, Launer LJ, Younkin SG, Dartigues JF, Corcoran C, Ikram MA, Dickson DW, Nicolas G, Campion D, Tschanz J, Schmidt H, Hakonarson H, Clarimon J, Munger R, Schmidt R, Farrer LA, Van Broeckhoven C, O'Donovan MC, DeStefano AL, Jones L, Haines JL, Deleuze JF, Owen MJ, Gudnason V, Mayeux R, Escott-Price V, Psaty BM, Ramirez A, Wang LS, Ruiz A, van Duijn CM, Holmans PA, Seshadri S, Williams J, Amouyel P, Schellenberg GD, Lambert JC, Pericak-Vance MA.
PMID: 31417202
Nat Genet. 2019 Sep;51(9):1423-1424. doi: 10.1038/s41588-019-0495-7.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Incomplete annotation has a disproportionate impact on our understanding of Mendelian and complex neurogenetic disorders.

Science advances

Zhang D, Guelfi S, Garcia-Ruiz S, Costa B, Reynolds RH, D'Sa K, Liu W, Courtin T, Peterson A, Jaffe AE, Hardy J, Botía JA, Collado-Torres L, Ryten M.
PMID: 32917675
Sci Adv. 2020 Jun 10;6(24). doi: 10.1126/sciadv.aay8299. Print 2020 Jun.

Growing evidence suggests that human gene annotation remains incomplete; however, it is unclear how this affects different tissues and our understanding of different disorders. Here, we detect previously unannotated transcription from Genotype-Tissue Expression RNA sequencing data across 41 human...

Amyloid precursor protein processing in human neurons with an allelic series of the .

Brain communications

Arber C, Villegas-Llerena C, Toombs J, Pocock JM, Ryan NS, Fox NC, Zetterberg H, Hardy J, Wray S.
PMID: 32395715
Brain Commun. 2019;1(1):fcz024. doi: 10.1093/braincomms/fcz024. Epub 2019 Oct 14.

Mutations in presenilin-1 (

Validating the Cognitive Scale for Down Syndrome (CS-DS) to Detect Longitudinal Cognitive Decline in Adults With Down Syndrome.

Frontiers in psychiatry

Startin CM, Lowe B, Hamburg S, Hithersay R, Strydom A.
PMID: 31057430
Front Psychiatry. 2019 Apr 16;10:158. doi: 10.3389/fpsyt.2019.00158. eCollection 2019.

Down syndrome (DS) is associated with intellectual disability and an ultra-high risk of developing dementia. Informant ratings are invaluable to assess abilities and related changes in adults with DS, particularly for those with more severe intellectual disabilities and/or cognitive...

A comprehensive analysis of methods for assessing polygenic burden on Alzheimer's disease pathology and risk beyond .

Brain communications

Altmann A, Scelsi MA, Shoai M, de Silva E, Aksman LM, Cash DM, Hardy J, Schott JM.
PMID: 32226939
Brain Commun. 2020;2(1):fcz047. doi: 10.1093/braincomms/fcz047. Epub 2019 Dec 16.

Genome-wide association studies have identified dozens of loci that alter the risk to develop Alzheimer's disease. However, with the exception of the

Correction: Alzheimer's disease polygenic risk score as a predictor of conversion from mild-cognitive impairment.

Translational psychiatry

Chaudhury S, Brookes KJ, Patel T, Fallows A, Guetta-Baranes T, Turton JC, Guerreiro R, Bras J, Hardy J, Francis PT, Croucher R, Holmes C, Morgan K.
PMID: 31186402
Transl Psychiatry. 2019 Jun 11;9(1):167. doi: 10.1038/s41398-019-0503-9.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Showing 1 to 12 of 15 entries