Journal article
TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions
MD Gallagher, E Suh, M Grossman, L Elman, L McCluskey, JC Van Swieten, S Al-Sarraj, M Neumann, E Gelpi, B Ghetti, JD Rohrer, G Halliday, C Van Broeckhoven, D Seilhean, PJ Shaw, MP Frosch, I Alafuzoff, A Antonell, N Bogdanovic, W Brooks Show all
Acta Neuropathologica | Published : 2014
Abstract
Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at..
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Awarded by Alzheimer’s Research UK
Funding Acknowledgements
Sources of support for this project include the NIH (AG033101, NS082265, P50 AG005133), The Neurological Tissue Bank of the Biobanc-HC-IDIBAPS, Hersenstichting project BG2010.02, Alzheimer Nederland/NIBC 056-13-018, Stichting Dioraphte projectnr 0802100, The National Institute for Health Research, SOPHIA, EuroMotor, National Health and Medical Research Council of Australia (NHMRC) (FTLD cases supported by NHMRC program grant 1037746), and Neuroscience Research Australia, University of New South Wales. The Antwerp site is in part funded by the MetLife Foundation, USA; the Interuniversity Attraction Poles program of the Belgian Science Policy Office (BELSPO), the Europe Initiative on Centers of Excellence in Neurodegeneration (CoEN) and the Methusalem program supported by the Flemish Government; the Foundation Alzheimer Research (SAO/FRA); the Medical Foundation Queen Elisabeth; the Research Foundation Flanders (FWO); the Agency for Innovation by Science and Technology Flanders (IWT), the University of Antwerp Research Fund, Belgium. The FWO provided a postdoctoral fellowship to J.v.d.Z and I.G. Alice Chen-Plotkin is also supported by the Burroughs Wellcome Fund Career Award for Medical Scientists, a Doris Duke Clinician Scientist Development Award, and the Benaroya Fund. Glenda Halliday holds a NHMRC Senior Principal Research Fellowship. Jonathan D. Rohrer and Martin Rosser are supported by the NIHR Queen Square Dementia Biomedical Research unit and work at the UCL Institute of Neurology Dementia Research Centre which is supported by Alzheimer's Research UK, Brain Research Trust, and The Wolfson Foundation.