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Article Dans Une Revue Journal of Alzheimer's Disease Année : 2021

A Novel Genetic Marker for the C9orf72 Repeat Expansion in the Finnish Population

Hannah Rostalski
  • Fonction : Auteur
Ville Korhonen
  • Fonction : Auteur
Teemu Kuulasmaa
  • Fonction : Auteur
Eino Solje
  • Fonction : Auteur
Johanna Krüger
  • Fonction : Auteur
Finn Gen
  • Fonction : Auteur
Karri Kaivola
  • Fonction : Auteur
Per Kristian Eide
  • Fonction : Auteur
Valtteri Julkunen
  • Fonction : Auteur
Pentti Tienari
  • Fonction : Auteur
Anne Remes
  • Fonction : Auteur
Ville Leinonen
  • Fonction : Auteur
Mikko Hiltunen
  • Fonction : Auteur
Annakaisa Haapasalo
  • Fonction : Auteur

Résumé

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

Dates et versions

hal-04277993 , version 1 (09-11-2023)

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Citer

Hannah Rostalski, Ville Korhonen, Teemu Kuulasmaa, Eino Solje, Johanna Krüger, et al.. A Novel Genetic Marker for the C9orf72 Repeat Expansion in the Finnish Population. Journal of Alzheimer's Disease, 2021, 83 (3), pp.1325-1332. ⟨10.3233/JAD-210599⟩. ⟨hal-04277993⟩
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