Genome-wide association study in essential tremor identifies three new loci

被引：63

作者：

Mueller, Stefanie H. ^{[1
]}

Girard, Simon L. ^{[2
,3
]}

Hopfner, Franziska ^{[1
]}

Merner, Nancy D. ^{[3
,4
]}

Bourassa, Cynthia V. ^{[3
]}

Lorenz, Delia ^{[5
]}

Clark, Lorraine N. ^{[6
]}

Tittmann, Lukas ^{[7
,8
]}

Soto-Ortolaza, Alexandra I. ^{[9
]}

Klebe, Stephan ^{[10
,11
]}

Hallett, Mark ^{[12
]}

Schneider, Susanne A. ^{[1
,13
]}

Hodgkinson, Colin A. ^{[14
]}

Lieb, Wolfgang ^{[8
]}

Wszolek, Zbigniew K. ^{[9
]}

Pendziwiat, Manuela ^{[15
]}

Lorenzo-Betancor, Oswaldo ^{[16
,17
]}

Poewe, Werner ^{[18
]}

Ortega-Cubero, Sara ^{[16
,17
]}

Seppi, Klaus ^{[18
]}

Rajput, Alex ^{[19
,20
]}

Hussl, Anna ^{[18
]}

Rajput, Ali H. ^{[19
,20
]}

Berg, Daniela ^{[1
]}

Dion, Patrick A. ^{[3
]}

Wurster, Isabel ^{[21
,22
]}

Shulman, Joshua M. ^{[23
,24
,25
,26
,27
]}

Srulijes, Karin ^{[21
,22
]}

Haubenberger, Dietrich ^{[12
]}

Pastor, Pau ^{[16
,17
]}

Vilarino-Guell, Carles ^{[28
]}

Postuma, Ronald B. ^{[3
,29
]}

Bernard, Genevieve ^{[3
,30
,31
,32
]}

Ladwig, Karl-Heinz ^{[33
,34
]}

Dupre, Nicolas ^{[35
]}

Jankovic, Joseph ^{[38
]}

Strauch, Konstantin ^{[36
,37
]}

Panisset, Michel ^{[38
]}

Winkelmann, Juliane ^{[39
,40
,41
]}

Testa, Claudia M. ^{[42
,43
]}

Zeuner, Kirsten E. ^{[1
]}

Reischl, Eva ^{[33
,44
]}

Ross, Owen A. ^{[9
]}

Arzberger, Thomas ^{[45
,46
]}

Chouinard, Sylvain ^{[38
]}

Deuschl, Guenther ^{[1
]}

Louis, Elan D. ^{[47
]}

Kuhlenbaeumer, Gregor ^{[1
]}

Rouleau, Guy A. ^{[3
]}

机构：

[1] Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Dept Neurol, Kiel, Germany

[2] Univ Quebec Chicoutimi, Dept Sci Fondamentales, Saguenay, PQ, Canada

[3] McGill Univ, Dept Neurol & Neurosurg, Montreal Neurol Inst, Montreal, PQ, Canada

[4] Auburn Univ, Dept Drug Discovery & Dev, Harrison Sch Pharm, Auburn, AL 36849 USA

[5] Univ Wurzburg, Univ Childrens Hosp, Wurzburg, Germany

[6] Columbia Univ, Taub Inst, Dept Pathol & Cell Biol, New York, NY USA

[7] Christian Albrechts Univ Kiel, Inst Epidemiol, Kiel, Germany

[8] Biobank POPGEN, Kiel, Germany

[9] Mayo Clin, Dept Neurosci & Neurol, Jacksonville, FL USA

[10] Univ Hosp Wurzburg, Dept Neurol, Wurzburg, Germany

[11] Univ Hosp Freiburg, Dept Neurol, Freiburg, Germany

[12] NINDS, Intramural Res Program, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

[13] Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany

[14] NIAAA, NIH, Bethesda, MD USA

[15] Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Dept Paediat Neurol, Kiel, Germany

[16] Univ Navarra, CIBERNED, Ctr Investi Biomed Red Enfermedades Neurodegenera, Neurogenet,Div Neurosci,Ctr Appl Med Res CIMA, E-31080 Pamplona, Spain

[17] Univ Barcelona, Hosp Univ Mutua Terrassa, Dept Neurol, Barcelona, Spain

[18] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria

[19] Univ Saskatchewan, Saskatoon, SK, Canada

[20] Saskatoon Hlth Reg, Saskatoon, SK, Canada

[21] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany

[22] German Ctr Neurodegenerat Dis, Tubingen, Germany

[23] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA

[24] Texas Childrens Hosp, Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[25] Texas Childrens Hosp, Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA

[26] Texas Childrens Hosp, Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA

[27] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA

[28] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada

[29] Montreal Gen Hosp, Dept Neurol, Montreal, PQ, Canada

[30] Montreal Childrens Hosp, Div Pediat Neurol, Dept Pediat, Montreal, PQ, Canada

[31] Montreal Childrens Hosp, Div Pediat Neurol, Dept Neurol, Montreal, PQ, Canada

[32] Montreal Childrens Hosp, Div Pediat Neurol, Dept Neurosurg, Montreal, PQ, Canada

[33] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany

[34] Tech Univ Munich, Klinikum Rechts Isar, Dept Psychosomat Med & Psychotherapy, Munich, Germany

[35] Univ Laval, CHU Quebec Enfant Jesus, Fac Med, Quebec City, PQ, Canada

[36] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany

[37] Ludwig Maximilians Univ Munchen, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany

[38] Ctr Hosp Univ Montreal, Unite Troubles mouvement Andre Barbeau, Montreal, PQ, Canada

[39] Helmholtz Zentrum Munchen, Inst Neurogen, Munich, Germany

[40] Tech Univ Munich, Klinikum Rechts Isar, Neurol Klin & Poliklin, Munich, Germany

[41] Munich Cluster Syst Neurol Synergy, Munich, Germany

[42] Virginia Commonwealth Univ, Dept Neurol, Richmond, VA USA

[43] Virginia Commonwealth Univ, Parkinsons & Movement Disorders Ctr, Richmond, VA USA

[44] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany

[45] Univ Munich, Ctr Neuropathol & Prion Res, D-80539MU Munich, Germany

[46] Ludwig Maximilians Univ Munchen, Ctr Neuropathol & Prion Res, Munich, Germany

[47] Yale Univ, Yale Sch Med, Dept Neurol, New Haven, CT USA

来源：

BRAIN | 2016年 / 139卷

基金：

美国国家卫生研究院;

关键词：

genome-wide association study; movement disorders; tremor; genetics; essential tremor; QUALITY-CONTROL; DISEASE; GENETICS; TOOL;

D O I：

10.1093/brain/aww242

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

We conducted a genome-wide association study of essential tremor, a common movement disorder characterized mainly by a postural and kinetic tremor of the upper extremities. Twin and family history studies show a high heritability for essential tremor. The molecular genetic determinants of essential tremor are unknown. We included 2807 patients and 6441 controls of European descent in our two-stage genome-wide association study. The 59 most significantly disease-associated markers of the discovery stage were genotyped in the replication stage. After Bonferroni correction two markers, one (rs10937625) located in the serine/threonine kinase STK32B and one (rs17590046) in the transcriptional coactivator PPARGC1A were associated with essential tremor. Three markers (rs12764057, rs10822974, rs7903491) in the cell-adhesion molecule CTNNA3 were significant in the combined analysis of both stages. The expression of STK32B was increased in the cerebellar cortex of patients and expression quantitative trait loci database mining showed association between the protective minor allele of rs10937625 and reduced expression in cerebellar cortex. We found no expression differences related to disease status or marker genotype for the other two genes. Replication of two lead single nucleotide polymorphisms of previous small genome-wide association studies (rs3794087 in SLC1A2, rs9652490 in LINGO1) did not confirm the association with essential tremor.

引用

页码：3163 / 3169

页数：7

共 50 条

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Mueller, S. H.
Girard, S. L.
Hopfner, F.
Merner, N. D.
Bourassa, C. V.
Lorenz, D.
Clark, L. N.
Tittmann, L.
Soto-Ortolaza, A. I.
Klebe, S.
Hallett, M.
Schneider, S. A.
Hodgkinson, C. A.
Lieb, W.
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Pendziwiat, M.
Lorenzo-Betancor, O.
Poewe, W.
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Seppi, K.
Rajput, A.
Hussl, A.
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Ross, O. A.
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