Genetic epidemiology of motor neuron disease-associated variants in the Scottish population

Holly A. Black; Danielle J. Leighton; Elaine M. Cleary; Elaine Rose; Laura Stephenson; Shuna Colville; David Ross; Jon Warner; Mary Porteous; George H. Gorrie; Robert Swingler; David Goldstein; Matthew B. Harms; Peter Connick; Suvankar Pal; Timothy J. Aitman; Siddharthan Chandran

doi:10.1016/j.neurobiolaging.2016.12.013

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population

Holly A. Black, Danielle J. Leighton, Elaine M. Cleary, Elaine Rose, Laura Stephenson, Shuna Colville, David Ross, Jon Warner, Mary Porteous, George H. Gorrie, Robert Swingler, David Goldstein, Matthew B. Harms, Peter Connick, Suvankar Pal, Timothy J. Aitman, Siddharthan Chandran

Research output: Contribution to journal › Article › peer-review

Abstract

Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant. Loss-of-function variants were found in TBK1 in 3 cases and no controls and, separately, in NEK1 in 3 cases and no controls. This study provides an accurate description of the genetic epidemiology of MND in Scotland and provides support for the contribution of both TBK1 and NEK1 to MND susceptibility in the Scottish population.

Original language	English
Pages (from-to)	178.e11-178.e20
Number of pages	10
Journal	Neurobiology of Aging
Volume	51
Early online date	21 Dec 2016
DOIs	https://doi.org/10.1016/j.neurobiolaging.2016.12.013
Publication status	Published - 31 Mar 2017

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Suvankar Pal
- Deanery of Clinical Sciences - Personal Chair of Neurodegenerative Disorders and Clinical T
- Edinburgh Neuroscience
- Centre for Clinical Brain Sciences
- Anne Rowling Regenerative Neurology Clinic
- Euan MacDonald Centre for Motor Neuron Disease Research
Person: Academic: Research Active

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Black, H. A., Leighton, D. J., Cleary, E. M., Rose, E., Stephenson, L., Colville, S., Ross, D., Warner, J., Porteous, M., Gorrie, G. H., Swingler, R., Goldstein, D., Harms, M. B., Connick, P., Pal, S., Aitman, T. J., & Chandran, S. (2017). Genetic epidemiology of motor neuron disease-associated variants in the Scottish population. Neurobiology of Aging, 51, 178.e11-178.e20. https://doi.org/10.1016/j.neurobiolaging.2016.12.013

@article{63af36b56d1345459ab57a7532320198,

title = "Genetic epidemiology of motor neuron disease-associated variants in the Scottish population",

abstract = "Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant. Loss-of-function variants were found in TBK1 in 3 cases and no controls and, separately, in NEK1 in 3 cases and no controls. This study provides an accurate description of the genetic epidemiology of MND in Scotland and provides support for the contribution of both TBK1 and NEK1 to MND susceptibility in the Scottish population.",

author = "Black, {Holly A.} and Leighton, {Danielle J.} and Cleary, {Elaine M.} and Elaine Rose and Laura Stephenson and Shuna Colville and David Ross and Jon Warner and Mary Porteous and Gorrie, {George H.} and Robert Swingler and David Goldstein and Harms, {Matthew B.} and Peter Connick and Suvankar Pal and Aitman, {Timothy J.} and Siddharthan Chandran",

year = "2017",

month = mar,

day = "31",

doi = "10.1016/j.neurobiolaging.2016.12.013",

language = "English",

volume = "51",

pages = "178.e11--178.e20",

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Black, HA, Leighton, DJ, Cleary, EM, Rose, E, Stephenson, L, Colville, S, Ross, D, Warner, J, Porteous, M, Gorrie, GH, Swingler, R, Goldstein, D, Harms, MB, Connick, P , Pal, S , Aitman, TJ & Chandran, S 2017, 'Genetic epidemiology of motor neuron disease-associated variants in the Scottish population', Neurobiology of Aging, vol. 51, pp. 178.e11-178.e20. https://doi.org/10.1016/j.neurobiolaging.2016.12.013

TY - JOUR

T1 - Genetic epidemiology of motor neuron disease-associated variants in the Scottish population

AU - Black, Holly A.

AU - Leighton, Danielle J.

AU - Cleary, Elaine M.

AU - Rose, Elaine

AU - Stephenson, Laura

AU - Colville, Shuna

AU - Ross, David

AU - Warner, Jon

AU - Porteous, Mary

AU - Gorrie, George H.

AU - Swingler, Robert

AU - Goldstein, David

AU - Harms, Matthew B.

AU - Connick, Peter

AU - Pal, Suvankar

AU - Aitman, Timothy J.

AU - Chandran, Siddharthan

PY - 2017/3/31

Y1 - 2017/3/31

N2 - Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant. Loss-of-function variants were found in TBK1 in 3 cases and no controls and, separately, in NEK1 in 3 cases and no controls. This study provides an accurate description of the genetic epidemiology of MND in Scotland and provides support for the contribution of both TBK1 and NEK1 to MND susceptibility in the Scottish population.

AB - Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant. Loss-of-function variants were found in TBK1 in 3 cases and no controls and, separately, in NEK1 in 3 cases and no controls. This study provides an accurate description of the genetic epidemiology of MND in Scotland and provides support for the contribution of both TBK1 and NEK1 to MND susceptibility in the Scottish population.

U2 - 10.1016/j.neurobiolaging.2016.12.013

DO - 10.1016/j.neurobiolaging.2016.12.013

M3 - Article

SN - 0197-4580

VL - 51

SP - 178.e11-178.e20

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population

Abstract

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