RT Journal Article
SR Electronic
T1 No rare deleterious variants from <em>STK32B</em>, <em>PPARGC1A</em>, and <em>CTNNA3</em> are associated with essential tremor
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams &amp; Wilkins
SP e195
DO 10.1212/NXG.0000000000000195
VO 3
IS 5
A1 Gabrielle Houle
A1 Amirthagowri Ambalavanan
A1 Jean-François Schmouth
A1 Claire S. Leblond
A1 Dan Spiegelman
A1 Sandra B. Laurent
A1 Cynthia V. Bourassa
A1 Celene Grayson
A1 Michel Panisset
A1 Sylvain Chouinard
A1 Nicolas Dupré
A1 Carles Vilariño-Güell
A1 Alex Rajput
A1 Simon L. Girard
A1 Patrick A. Dion
A1 Guy A. Rouleau
YR 2017
UL http://ng.neurology.org/content/3/5/e195.abstract
AB Objective: To assess the contribution of variants in STK32B, PPARGC1A, and CTNNA3 as essential tremor (ET) predisposing factors following their association in a 2-stage genome-wide association study (GWAS).Methods: The coding regions of these genes was examined for the presence of rare variants using two approaches: (1) Looking at whole-exome and whole-genome sequencing data of 14 autosomal dominant multiplex ET families. (2) Conducting a targeted massive parallel sequencing to examine the three genes in cohorts of 269 ET cases and 287 control individuals. The cumulative impact of rare variants was assessed using SKAT-O analyses using (1) all variants, (2) only rare variants, and (3) only the rare variants altering the mRNA.Results: Thirty-four variants were identified. No difference emerged regarding the distributions of individual variants (or gene) between cases and controls.Conclusion: No rare exonic variants further validated one of these genes as a risk factor for ET. The recent GWAS offers promising avenues, but the genetic heterogeneity of ET is nonetheless challenging for the validation of risk factors, and ultimately larger cohorts of cases should help to overcome this task.ET=essential tremor; ExAC=Exome Aggregation Consortium; GWAS=genome-wide association study; QC=quality control; SKAT-O=sequence kernel association test; WES=whole-exome sequencing; WGS=whole-genome sequencing