University of Oulu

Rostalski, Hannah et al. ‘A Novel Genetic Marker for the C9orf72 Repeat Expansion in the Finnish Population’. 1 Jan. 2021 : 1325 – 1332.

A novel genetic marker for the C9orf72 repeat expansion in the Finnish population

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Author: Rostalski, Hannah1; Korhonen, Ville2; Kuulasmaa, Teemu3;
Organizations: 1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
2Neurocenter, Neurosurgery, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
3Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
4Institute of Clinical Medicine - Neurology, University of Eastern Finland
5Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland
6Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
7Medical Research Center (MRC), Oulu University Hospital, Oulu, Finland
8Department of Neurology, Helsinki University Hospital and Translational Immunology Program, Biomedicum, University of Helsinki, Helsinki, Finland
9Oslo University Hospital-Rikshospitalet; and Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway
10Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE facteurs de risque et d´eterminants mol´eculaires des maladies li´es au vieillissement, Lille, France
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.9 MB)
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Language: English
Published: IOS Press, 2021
Publish Date: 2023-03-06


Background: C9orf72 repeat expansion (C9exp) is the most common genetic cause underlying frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, detection of the C9exprequires elaborative methods.

Objective: Identification of C9exp carriers from genotyped cohorts could be facilitated by using single nucleotide polymorphisms (SNPs) as markers for the C9exp.

Methods: We elucidated the potential of the previously described Finnish risk haplotype, defined by the SNP rs3849942, to identify potential C9exp carriers among 218,792 Finns using the FinnGen database. The haplotype approach was first tested in an idiopathic normal pressure hydrocephalus (iNPH) patient cohort (European Alzheimer’s Disease DNA BioBank) containing C9exp carriers by comparing intermediate (15–30) and full-length (> 60 repeats) C9exp carriers (n = 41) to C9exp negative patients (< 15 repeats, n = 801).

Results: In this analysis, rs3849942 was associated with carriership of C9exp (OR 8.44, p < 2 × 10–15), while the strongest association was found with rs139185008 (OR 39.4, p < 5 × 10–18). Unbiased analysis of rs139185008 in FinnGen showed the strongest association with FTLD (OR 4.38, 3 × 10–15) and motor neuron disease ALS (OR 5.19, 3 × 10–21). rs139185008 was the top SNP in all diseases (iNPH, FTLD, ALS), and further showed a strong association with ALS in the UK Biobank (p = 9.0 × 10–8).

Conclusions: Our findings suggest that rs139185008 is a useful marker to identify potential C9exp carriers in the genotyped cohorts and biobanks originating from Finland.

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Series: Journal of Alzheimer's disease
ISSN: 1387-2877
ISSN-E: 1875-8908
ISSN-L: 1387-2877
Volume: 83
Issue: 3
Pages: 1325 - 1332
DOI: 10.3233/JAD-210599
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
3111 Biomedicine
Funding: This work was supported by the Academy of Finland, under grant numbers 315459 (AH), 315460 (AMR), and 307866 (MH); the Strategic Neuroscience Funding of the University of Eastern Finland; Finnish Brain Foundation (ES), Sigrid Juselius Foundation (ES, MH, PJT), Finnish Cultural Foundation (KK) Instrumentarium Science Foundation (ES), Orion Research Foundation (ES). This work was supported by a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Programme – Neurodegenerative Disease Research (JPND). Inserm UMR1167 is also funded by Inserm, Institut Pasteur de Lille, the Lille Metropole Communauté Urbaine, the French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to Alzheimer’s disease). This publication is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 740264.
Academy of Finland Grant Number: 315460
Detailed Information: 315460 (Academy of Finland Funding decision)
Copyright information: © 2021 – IOS Press.