Mutations modifying sporadic Alzheimer's disease age of onset

J.I. Vélez, F. Lopera, H.R. Patel, A.S. Johar, Y. Cai, D. Rivera, C. Tobón, A. Villegas, D. Sepulveda-Falla, S.G. Lehmann, S. Easteal, C.A. Mastronardi, M. Arcos-Burgos

Resultado de la investigación: Contribución a una revistaArtículo

6 Citas (Scopus)

Resumen

The identification of mutations modifying the age of onset (AOO) in Alzheimer's disease (AD) is crucial for understanding the natural history of AD and, therefore, for early interventions. Patients with sporadic AD (sAD) from a genetic isolate in the extremes of the AOO distribution were whole-exome genotyped. Single- and multi-locus linear mixed-effects models were used to identify functional variants modifying AOO. A posteriori enrichment and bioinformatic analyses were applied to evaluate the non-random clustering of the associate variants to physiopathological pathways involved in AD. We identified more than 20 pathogenic, genome-wide statistically significant mutations of major modifier effect on the AOO. These variants are harbored in genes implicated in neuron apoptosis, neurogenesis, inflammatory processes linked to AD, oligodendrocyte differentiation, and memory processes. This set of new genes harboring these mutations could be of importance for prediction, follow-up and eventually as therapeutical targets of AD. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Idioma originalInglés estadounidense
Páginas (desde-hasta)1116-1130
Número de páginas15
PublicaciónAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volumen171
N.º8
DOI
EstadoPublicada - 2016
Publicado de forma externa

Huella dactilar

Age of Onset
Alzheimer Disease
Mutation
Exome
Age Distribution
Neurogenesis
Oligodendroglia
Computational Biology
Genes
Cluster Analysis
Genome
Neurons

Citar esto

Vélez, J. I., Lopera, F., Patel, H. R., Johar, A. S., Cai, Y., Rivera, D., ... Arcos-Burgos, M. (2016). Mutations modifying sporadic Alzheimer's disease age of onset. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 171(8), 1116-1130. https://doi.org/10.1002/ajmg.b.32493
Vélez, J.I. ; Lopera, F. ; Patel, H.R. ; Johar, A.S. ; Cai, Y. ; Rivera, D. ; Tobón, C. ; Villegas, A. ; Sepulveda-Falla, D. ; Lehmann, S.G. ; Easteal, S. ; Mastronardi, C.A. ; Arcos-Burgos, M. / Mutations modifying sporadic Alzheimer's disease age of onset. En: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2016 ; Vol. 171, N.º 8. pp. 1116-1130.
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abstract = "The identification of mutations modifying the age of onset (AOO) in Alzheimer's disease (AD) is crucial for understanding the natural history of AD and, therefore, for early interventions. Patients with sporadic AD (sAD) from a genetic isolate in the extremes of the AOO distribution were whole-exome genotyped. Single- and multi-locus linear mixed-effects models were used to identify functional variants modifying AOO. A posteriori enrichment and bioinformatic analyses were applied to evaluate the non-random clustering of the associate variants to physiopathological pathways involved in AD. We identified more than 20 pathogenic, genome-wide statistically significant mutations of major modifier effect on the AOO. These variants are harbored in genes implicated in neuron apoptosis, neurogenesis, inflammatory processes linked to AD, oligodendrocyte differentiation, and memory processes. This set of new genes harboring these mutations could be of importance for prediction, follow-up and eventually as therapeutical targets of AD. {\circledC} 2016 Wiley Periodicals, Inc. {\circledC} 2016 Wiley Periodicals, Inc.",
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Vélez, JI, Lopera, F, Patel, HR, Johar, AS, Cai, Y, Rivera, D, Tobón, C, Villegas, A, Sepulveda-Falla, D, Lehmann, SG, Easteal, S, Mastronardi, CA & Arcos-Burgos, M 2016, 'Mutations modifying sporadic Alzheimer's disease age of onset', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 171, n.º 8, pp. 1116-1130. https://doi.org/10.1002/ajmg.b.32493

Mutations modifying sporadic Alzheimer's disease age of onset. / Vélez, J.I.; Lopera, F.; Patel, H.R.; Johar, A.S.; Cai, Y.; Rivera, D.; Tobón, C.; Villegas, A.; Sepulveda-Falla, D.; Lehmann, S.G.; Easteal, S.; Mastronardi, C.A.; Arcos-Burgos, M.

En: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 171, N.º 8, 2016, p. 1116-1130.

Resultado de la investigación: Contribución a una revistaArtículo

TY - JOUR

T1 - Mutations modifying sporadic Alzheimer's disease age of onset

AU - Vélez, J.I.

AU - Lopera, F.

AU - Patel, H.R.

AU - Johar, A.S.

AU - Cai, Y.

AU - Rivera, D.

AU - Tobón, C.

AU - Villegas, A.

AU - Sepulveda-Falla, D.

AU - Lehmann, S.G.

AU - Easteal, S.

AU - Mastronardi, C.A.

AU - Arcos-Burgos, M.

N1 - Cited By :1 Export Date: 4 April 2018 CODEN: AJMGE

PY - 2016

Y1 - 2016

N2 - The identification of mutations modifying the age of onset (AOO) in Alzheimer's disease (AD) is crucial for understanding the natural history of AD and, therefore, for early interventions. Patients with sporadic AD (sAD) from a genetic isolate in the extremes of the AOO distribution were whole-exome genotyped. Single- and multi-locus linear mixed-effects models were used to identify functional variants modifying AOO. A posteriori enrichment and bioinformatic analyses were applied to evaluate the non-random clustering of the associate variants to physiopathological pathways involved in AD. We identified more than 20 pathogenic, genome-wide statistically significant mutations of major modifier effect on the AOO. These variants are harbored in genes implicated in neuron apoptosis, neurogenesis, inflammatory processes linked to AD, oligodendrocyte differentiation, and memory processes. This set of new genes harboring these mutations could be of importance for prediction, follow-up and eventually as therapeutical targets of AD. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

AB - The identification of mutations modifying the age of onset (AOO) in Alzheimer's disease (AD) is crucial for understanding the natural history of AD and, therefore, for early interventions. Patients with sporadic AD (sAD) from a genetic isolate in the extremes of the AOO distribution were whole-exome genotyped. Single- and multi-locus linear mixed-effects models were used to identify functional variants modifying AOO. A posteriori enrichment and bioinformatic analyses were applied to evaluate the non-random clustering of the associate variants to physiopathological pathways involved in AD. We identified more than 20 pathogenic, genome-wide statistically significant mutations of major modifier effect on the AOO. These variants are harbored in genes implicated in neuron apoptosis, neurogenesis, inflammatory processes linked to AD, oligodendrocyte differentiation, and memory processes. This set of new genes harboring these mutations could be of importance for prediction, follow-up and eventually as therapeutical targets of AD. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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DO - 10.1002/ajmg.b.32493

M3 - Article

VL - 171

SP - 1116

EP - 1130

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

SN - 1552-4841

IS - 8

ER -