Abstract

The hexanucleotide repeat expansion in C9orf72 is a common cause of amyotrophic lateral sclerosis/frontotemporal dementia and also rarely found in other psychiatric and neurodegenerative conditions. Alleles with >30 repeats are often considered an expansion, but the pathogenic repeat length threshold is still unclear. It is also unclear whether intermediate repeat length alleles (often defined either as 7-30 or 20-30 repeats) have clinically significant effects. We determined the C9orf72 repeat length distribution in 3142 older Finns (aged 60-104 years). The longest nonexpanded allele was 45 repeats. We found 7-45 repeats in 1036/3142 (33%) individuals, 20-45 repeats in 56/3142 (1.8%), 30-45 repeats in 12/3142 (0.38%), and expansion (>45 repeats) in 6/3142 (0.19%). There was no apparent clustering of neurodegenerative or psychiatric diseases in individuals with 30-45 repeats indicating that 30-45 repeats are not pathogenic. None of the 6 expansion carriers had a diagnosis of amyotrophic lateral sclerosis/frontotemporal dementia but 4 had a diagnosis of a neurodegenerative or psychiatric disease. Intermediate length alleles (categorized as 7-45 and 20-45 repeats) did not associate with Alzheimer's disease or cognitive impairment. (C) 2019 The Author(s). Published by Elsevier Inc.

Original languageEnglish
JournalNeurobiology of Aging
Volume84
Pages (from-to)242.e7-242.e12
Number of pages6
ISSN0197-4580
DOIs
Publication statusPublished - Dec 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 3124 Neurology and psychiatry
  • Genetics
  • Alzheimer's disease
  • Dementia
  • C9orf72
  • Cohort studies
  • HUNTINGTONS-DISEASE
  • ALZHEIMERS-DISEASE
  • EXPANSION
  • SIZE
  • ASSOCIATION
  • DEMENTIA
  • CHILDREN
  • GROWTH
  • BIRTH
  • AGE

Cite this

@article{8d8ab36e3fb34b4ebd0194a40fe2bc3e,
title = "C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition",
abstract = "The hexanucleotide repeat expansion in C9orf72 is a common cause of amyotrophic lateral sclerosis/frontotemporal dementia and also rarely found in other psychiatric and neurodegenerative conditions. Alleles with >30 repeats are often considered an expansion, but the pathogenic repeat length threshold is still unclear. It is also unclear whether intermediate repeat length alleles (often defined either as 7-30 or 20-30 repeats) have clinically significant effects. We determined the C9orf72 repeat length distribution in 3142 older Finns (aged 60-104 years). The longest nonexpanded allele was 45 repeats. We found 7-45 repeats in 1036/3142 (33{\%}) individuals, 20-45 repeats in 56/3142 (1.8{\%}), 30-45 repeats in 12/3142 (0.38{\%}), and expansion (>45 repeats) in 6/3142 (0.19{\%}). There was no apparent clustering of neurodegenerative or psychiatric diseases in individuals with 30-45 repeats indicating that 30-45 repeats are not pathogenic. None of the 6 expansion carriers had a diagnosis of amyotrophic lateral sclerosis/frontotemporal dementia but 4 had a diagnosis of a neurodegenerative or psychiatric disease. Intermediate length alleles (categorized as 7-45 and 20-45 repeats) did not associate with Alzheimer's disease or cognitive impairment. (C) 2019 The Author(s). Published by Elsevier Inc.",
keywords = "3124 Neurology and psychiatry, Genetics, Alzheimer's disease, Dementia, C9orf72, Cohort studies, HUNTINGTONS-DISEASE, ALZHEIMERS-DISEASE, EXPANSION, SIZE, ASSOCIATION, DEMENTIA, CHILDREN, GROWTH, BIRTH, AGE",
author = "Karri Kaivola and Anna Kiviharju and Lilja Jansson and Ville Rantalainen and Eriksson, {Johan G.} and Strandberg, {Timo E.} and Hannu Laaksovirta and Renton, {Alan E} and Traynor, {Bryan J.} and Liisa Myllykangas and Pentti Tienari",
year = "2019",
month = "12",
doi = "10.1016/j.neurobiolaging.2019.02.026",
language = "English",
volume = "84",
pages = "242.e7--242.e12",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC",

}

C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition. / Kaivola, Karri; Kiviharju, Anna; Jansson, Lilja; Rantalainen, Ville; Eriksson, Johan G.; Strandberg, Timo E.; Laaksovirta, Hannu; Renton, Alan E; Traynor, Bryan J.; Myllykangas, Liisa; Tienari, Pentti.

In: Neurobiology of Aging, Vol. 84, 12.2019, p. 242.e7-242.e12.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition

AU - Kaivola, Karri

AU - Kiviharju, Anna

AU - Jansson, Lilja

AU - Rantalainen, Ville

AU - Eriksson, Johan G.

AU - Strandberg, Timo E.

AU - Laaksovirta, Hannu

AU - Renton, Alan E

AU - Traynor, Bryan J.

AU - Myllykangas, Liisa

AU - Tienari, Pentti

PY - 2019/12

Y1 - 2019/12

N2 - The hexanucleotide repeat expansion in C9orf72 is a common cause of amyotrophic lateral sclerosis/frontotemporal dementia and also rarely found in other psychiatric and neurodegenerative conditions. Alleles with >30 repeats are often considered an expansion, but the pathogenic repeat length threshold is still unclear. It is also unclear whether intermediate repeat length alleles (often defined either as 7-30 or 20-30 repeats) have clinically significant effects. We determined the C9orf72 repeat length distribution in 3142 older Finns (aged 60-104 years). The longest nonexpanded allele was 45 repeats. We found 7-45 repeats in 1036/3142 (33%) individuals, 20-45 repeats in 56/3142 (1.8%), 30-45 repeats in 12/3142 (0.38%), and expansion (>45 repeats) in 6/3142 (0.19%). There was no apparent clustering of neurodegenerative or psychiatric diseases in individuals with 30-45 repeats indicating that 30-45 repeats are not pathogenic. None of the 6 expansion carriers had a diagnosis of amyotrophic lateral sclerosis/frontotemporal dementia but 4 had a diagnosis of a neurodegenerative or psychiatric disease. Intermediate length alleles (categorized as 7-45 and 20-45 repeats) did not associate with Alzheimer's disease or cognitive impairment. (C) 2019 The Author(s). Published by Elsevier Inc.

AB - The hexanucleotide repeat expansion in C9orf72 is a common cause of amyotrophic lateral sclerosis/frontotemporal dementia and also rarely found in other psychiatric and neurodegenerative conditions. Alleles with >30 repeats are often considered an expansion, but the pathogenic repeat length threshold is still unclear. It is also unclear whether intermediate repeat length alleles (often defined either as 7-30 or 20-30 repeats) have clinically significant effects. We determined the C9orf72 repeat length distribution in 3142 older Finns (aged 60-104 years). The longest nonexpanded allele was 45 repeats. We found 7-45 repeats in 1036/3142 (33%) individuals, 20-45 repeats in 56/3142 (1.8%), 30-45 repeats in 12/3142 (0.38%), and expansion (>45 repeats) in 6/3142 (0.19%). There was no apparent clustering of neurodegenerative or psychiatric diseases in individuals with 30-45 repeats indicating that 30-45 repeats are not pathogenic. None of the 6 expansion carriers had a diagnosis of amyotrophic lateral sclerosis/frontotemporal dementia but 4 had a diagnosis of a neurodegenerative or psychiatric disease. Intermediate length alleles (categorized as 7-45 and 20-45 repeats) did not associate with Alzheimer's disease or cognitive impairment. (C) 2019 The Author(s). Published by Elsevier Inc.

KW - 3124 Neurology and psychiatry

KW - Genetics

KW - Alzheimer's disease

KW - Dementia

KW - C9orf72

KW - Cohort studies

KW - HUNTINGTONS-DISEASE

KW - ALZHEIMERS-DISEASE

KW - EXPANSION

KW - SIZE

KW - ASSOCIATION

KW - DEMENTIA

KW - CHILDREN

KW - GROWTH

KW - BIRTH

KW - AGE

U2 - 10.1016/j.neurobiolaging.2019.02.026

DO - 10.1016/j.neurobiolaging.2019.02.026

M3 - Article

VL - 84

SP - 242.e7-242.e12

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -