Candidate variants in TUB are associated with familial tremor

M. Reza Sailani; Fereshteh Jahanbani; Charles W. Abbott; Hayan Lee; Amin Zia; Shannon Rego; Juliane Winkelmann; Franziska Hopfner; Tahir N. Khan; Nicholas Katsanis; Stefanie H. Müller; Daniela Berg; Katherine M. Lyman; Christian Mychajliw; Günther Deuschl; Jonathan A. Bernstein; Gregor Kuhlenbäumer; Michael P. Snyder

doi:10.1371/journal.pgen.1009010

Candidate variants in TUB are associated with familial tremor

M. Reza Sailani, Fereshteh Jahanbani, Charles W. Abbott, Hayan Lee, Amin Zia, Shannon Rego, Juliane Winkelmann, Franziska Hopfner, Tahir N. Khan, Nicholas Katsanis, Stefanie H. Müller, Daniela Berg, Katherine M. Lyman, Christian Mychajliw, Günther Deuschl, Jonathan A. Bernstein, Gregor Kuhlenbäumer, Michael P. Snyder

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2 Scopus citations

Abstract

Essential tremor (ET) is the most common adult-onset movement disorder. In the present study, we performed whole exome sequencing of a large ET-affected family (10 affected and 6 un-affected family members) and identified a TUB p.V431I variant (rs75594955) segregating in a manner consistent with autosomal-dominant inheritance. Subsequent targeted re-sequencing of TUB in 820 unrelated individuals with sporadic ET and 630 controls revealed significant enrichment of rare nonsynonymous TUB variants (e.g. rs75594955: p. V431I, rs1241709665: p.Ile20Phe, rs55648406: p.Arg49Gln) in the ET cohort (SKAT-O test p-value = 6.20e-08). TUB encodes a transcription factor predominantly expressed in neuronal cells and has been previously implicated in obesity. ChIP-seq analyses of the TUB transcription factor across different regions of the mouse brain revealed that TUB regulates the pathways responsible for neurotransmitter production as well thyroid hormone signaling. Together, these results support the association of rare variants in TUB with ET.

Original language	English
Article number	1009010
Pages (from-to)	e1009010
Journal	PLoS Genetics
Volume	16
Issue number	9
DOIs	https://doi.org/10.1371/journal.pgen.1009010
State	Published - Sep 2020

Keywords

Adaptor Proteins, Signal Transducing/genetics
Aged
Aged, 80 and over
Animals
Chromatin Immunoprecipitation Sequencing/methods
Cohort Studies
Essential Tremor/genetics
Exome Sequencing/methods
Exome/genetics
Family
Female
Humans
Male
Mice, Inbred C57BL
Middle Aged
Pedigree
Polymorphism, Single Nucleotide/genetics
Transcription Factors/genetics

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10.1371/journal.pgen.1009010

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Reza Sailani, M., Jahanbani, F., Abbott, C. W., Lee, H., Zia, A., Rego, S., Winkelmann, J., Hopfner, F., Khan, T. N., Katsanis, N., Müller, S. H., Berg, D., Lyman, K. M., Mychajliw, C., Deuschl, G., Bernstein, J. A., Kuhlenbäumer, G., & Snyder, M. P. (2020). Candidate variants in TUB are associated with familial tremor. PLoS Genetics, 16(9), e1009010. Article 1009010. https://doi.org/10.1371/journal.pgen.1009010

@article{6061d8d853814f789fa3308facac9e1d,

title = "Candidate variants in TUB are associated with familial tremor",

abstract = "Essential tremor (ET) is the most common adult-onset movement disorder. In the present study, we performed whole exome sequencing of a large ET-affected family (10 affected and 6 un-affected family members) and identified a TUB p.V431I variant (rs75594955) segregating in a manner consistent with autosomal-dominant inheritance. Subsequent targeted re-sequencing of TUB in 820 unrelated individuals with sporadic ET and 630 controls revealed significant enrichment of rare nonsynonymous TUB variants (e.g. rs75594955: p. V431I, rs1241709665: p.Ile20Phe, rs55648406: p.Arg49Gln) in the ET cohort (SKAT-O test p-value = 6.20e-08). TUB encodes a transcription factor predominantly expressed in neuronal cells and has been previously implicated in obesity. ChIP-seq analyses of the TUB transcription factor across different regions of the mouse brain revealed that TUB regulates the pathways responsible for neurotransmitter production as well thyroid hormone signaling. Together, these results support the association of rare variants in TUB with ET.",

keywords = "Adaptor Proteins, Signal Transducing/genetics, Aged, Aged, 80 and over, Animals, Chromatin Immunoprecipitation Sequencing/methods, Cohort Studies, Essential Tremor/genetics, Exome Sequencing/methods, Exome/genetics, Family, Female, Humans, Male, Mice, Inbred C57BL, Middle Aged, Pedigree, Polymorphism, Single Nucleotide/genetics, Transcription Factors/genetics",

author = "{Reza Sailani}, M. and Fereshteh Jahanbani and Abbott, {Charles W.} and Hayan Lee and Amin Zia and Shannon Rego and Juliane Winkelmann and Franziska Hopfner and Khan, {Tahir N.} and Nicholas Katsanis and M{\"u}ller, {Stefanie H.} and Daniela Berg and Lyman, {Katherine M.} and Christian Mychajliw and G{\"u}nther Deuschl and Bernstein, {Jonathan A.} and Gregor Kuhlenb{\"a}umer and Snyder, {Michael P.}",

note = "Publisher Copyright: {\textcopyright} 2020 Sailani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2020",

month = sep,

doi = "10.1371/journal.pgen.1009010",

language = "English",

volume = "16",

pages = "e1009010",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "9",

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Reza Sailani, M, Jahanbani, F, Abbott, CW, Lee, H, Zia, A, Rego, S, Winkelmann, J, Hopfner, F, Khan, TN, Katsanis, N, Müller, SH, Berg, D, Lyman, KM, Mychajliw, C, Deuschl, G, Bernstein, JA, Kuhlenbäumer, G & Snyder, MP 2020, 'Candidate variants in TUB are associated with familial tremor', PLoS Genetics, vol. 16, no. 9, 1009010, pp. e1009010. https://doi.org/10.1371/journal.pgen.1009010

TY - JOUR

T1 - Candidate variants in TUB are associated with familial tremor

AU - Reza Sailani, M.

AU - Jahanbani, Fereshteh

AU - Abbott, Charles W.

AU - Lee, Hayan

AU - Zia, Amin

AU - Rego, Shannon

AU - Winkelmann, Juliane

AU - Hopfner, Franziska

AU - Khan, Tahir N.

AU - Katsanis, Nicholas

AU - Müller, Stefanie H.

AU - Berg, Daniela

AU - Lyman, Katherine M.

AU - Mychajliw, Christian

AU - Deuschl, Günther

AU - Bernstein, Jonathan A.

AU - Kuhlenbäumer, Gregor

AU - Snyder, Michael P.

N1 - Publisher Copyright: © 2020 Sailani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2020/9

Y1 - 2020/9

N2 - Essential tremor (ET) is the most common adult-onset movement disorder. In the present study, we performed whole exome sequencing of a large ET-affected family (10 affected and 6 un-affected family members) and identified a TUB p.V431I variant (rs75594955) segregating in a manner consistent with autosomal-dominant inheritance. Subsequent targeted re-sequencing of TUB in 820 unrelated individuals with sporadic ET and 630 controls revealed significant enrichment of rare nonsynonymous TUB variants (e.g. rs75594955: p. V431I, rs1241709665: p.Ile20Phe, rs55648406: p.Arg49Gln) in the ET cohort (SKAT-O test p-value = 6.20e-08). TUB encodes a transcription factor predominantly expressed in neuronal cells and has been previously implicated in obesity. ChIP-seq analyses of the TUB transcription factor across different regions of the mouse brain revealed that TUB regulates the pathways responsible for neurotransmitter production as well thyroid hormone signaling. Together, these results support the association of rare variants in TUB with ET.

AB - Essential tremor (ET) is the most common adult-onset movement disorder. In the present study, we performed whole exome sequencing of a large ET-affected family (10 affected and 6 un-affected family members) and identified a TUB p.V431I variant (rs75594955) segregating in a manner consistent with autosomal-dominant inheritance. Subsequent targeted re-sequencing of TUB in 820 unrelated individuals with sporadic ET and 630 controls revealed significant enrichment of rare nonsynonymous TUB variants (e.g. rs75594955: p. V431I, rs1241709665: p.Ile20Phe, rs55648406: p.Arg49Gln) in the ET cohort (SKAT-O test p-value = 6.20e-08). TUB encodes a transcription factor predominantly expressed in neuronal cells and has been previously implicated in obesity. ChIP-seq analyses of the TUB transcription factor across different regions of the mouse brain revealed that TUB regulates the pathways responsible for neurotransmitter production as well thyroid hormone signaling. Together, these results support the association of rare variants in TUB with ET.

KW - Adaptor Proteins, Signal Transducing/genetics

KW - Aged

KW - Aged, 80 and over

KW - Animals

KW - Chromatin Immunoprecipitation Sequencing/methods

KW - Cohort Studies

KW - Essential Tremor/genetics

KW - Exome Sequencing/methods

KW - Exome/genetics

KW - Family

KW - Female

KW - Humans

KW - Male

KW - Mice, Inbred C57BL

KW - Middle Aged

KW - Pedigree

KW - Polymorphism, Single Nucleotide/genetics

KW - Transcription Factors/genetics

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U2 - 10.1371/journal.pgen.1009010

DO - 10.1371/journal.pgen.1009010

M3 - Article

C2 - 32956375

SN - 1553-7390

VL - 16

SP - e1009010

JO - PLoS Genetics

JF - PLoS Genetics

IS - 9

M1 - 1009010

ER -

Candidate variants in TUB are associated with familial tremor

Abstract

Keywords

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