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

TitelGenome-wide association study in essential tremor identifies three new loci.
MedientypJournal Article
Jahr der Veröffentlichung2016
AutorenMüller SH, Girard SL, Hopfner F, Merner ND, Bourassa CV, Lorenz D, Clark LN, Tittmann L, Soto-Ortolaza AI, Klebe S, Hallett M, Schneider SA, Hodgkinson CA, Lieb W, Wszolek ZK, Pendziwiat M, Lorenzo-Betancor O, Poewe W, Ortega-Cubero S, Seppi K, Rajput A, Hussl A, Rajput AH, Berg D, Dion PA, Wurster I, Shulman JM, Srulijes K, Haubenberger D, Pastor P, Vilariño-Güell C, Postuma RB, Bernard G, Ladwig K-H, Dupré N, Jankovic J, Strauch K, Panisset M, Winkelmann J, Testa CM, Reischl E, Zeuner KE, Ross OA, Arzberger T, Chouinard S, Deuschl G, Louis ED, Kuhlenbäumer G, Rouleau GA
JournalBrain
Volume139
AusgabePt 12
Pagination3163-3169
Datum der Veröffentlichung2016 12
ISSN1460-2156
Schlüsselwörteralpha Catenin, Essential Tremor, Genome-Wide Association Study, Humans, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Polymorphism, Single Nucleotide, Protein-Serine-Threonine Kinases
Zusammenfassung

<p>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.</p>

DOI10.1093/brain/aww242
Alternate JournalBrain
PubMed ID27797806
PubMed Central IDPMC5382938
Grant ListP50 AG025688 / AG / NIA NIH HHS / United States
P50 NS072187 / NS / NINDS NIH HHS / United States
R01 NS073872 / NS / NINDS NIH HHS / United States
/ / CIHR / Canada