PT  - JOURNAL ARTICLE
AU  - Gabrielle Houle
AU  - Amirthagowri Ambalavanan
AU  - Jean-François Schmouth
AU  - Claire S. Leblond
AU  - Dan Spiegelman
AU  - Sandra B. Laurent
AU  - Cynthia V. Bourassa
AU  - Celene Grayson
AU  - Michel Panisset
AU  - Sylvain Chouinard
AU  - Nicolas Dupré
AU  - Carles Vilariño-Güell
AU  - Alex Rajput
AU  - Simon L. Girard
AU  - Patrick A. Dion
AU  - Guy A. Rouleau
TI  - No rare deleterious variants from <em>STK32B</em>, <em>PPARGC1A</em>, and <em>CTNNA3</em> are associated with essential tremor
AID  - 10.1212/NXG.0000000000000195
DP  - 2017 Oct 01
TA  - Neurology Genetics
PG  - e195
VI  - 3
IP  - 5
4099  - http://ng.neurology.org/content/3/5/e195.short
4100  - http://ng.neurology.org/content/3/5/e195.full
SO  - Neurol Genet2017 Oct 01; 3
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