Dataset Information

Association of Essential Tremor With Novel Risk Loci: A Genome-Wide Association Study and Meta-analysis.

ABSTRACT:

Importance

Essential tremor (ET) is one of the most common movement disorders, affecting 5% of the general population older than 65 years. Common variants are thought to contribute toward susceptibility to ET, but no variants have been robustly identified.

Objective

To identify common genetic factors associated with risk of ET.

Design, setting, and participants

Case-control genome-wide association study. Inverse-variance meta-analysis was used to combine cohorts. Multicenter samples collected from European populations were collected from January 2010 to September 2019 as part of an ongoing study. Included patients were clinically diagnosed with or reported having ET. Control individuals were not diagnosed with or reported to have ET. Of 485 250 individuals, data for 483 054 passed data quality control and were used.

Main outcomes and measures

Genotypes of common variants associated with risk of ET.

Results

Of the 483 054 individuals included, there were 7177 with ET (3693 [51.46%] female; mean [SD] age, 62.66 [15.12] years), and 475 877 control individuals (253 785 [53.33%] female; mean [SD] age, 56.40 [17.6] years). Five independent genome-wide significant loci and were identified and were associated with approximately 18% of ET heritability. Functional analyses found significant enrichment in the cerebellar hemisphere, cerebellum, and axonogenesis pathways. Genetic correlation (r), which measures the degree of genetic overlap, revealed significant common variant overlap with Parkinson disease (r, 0.28; P = 2.38 × 10-8) and depression (r, 0.12; P = 9.78 × 10-4). A separate fine-mapping of transcriptome-wide association hits identified genes such as BACE2, LRRN2, DHRS13, and LINC00323 in disease-relevant brain regions, such as the cerebellum.

Conclusions and relevance

The results of this genome-wide association study suggest that a portion of ET heritability can be explained by common genetic variation and can help identify new common genetic risk factors for ET.

SUBMITTER: Liao C

PROVIDER: S-EPMC8728658 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Essential Tremor With Novel Risk Loci: A Genome-Wide Association Study and Meta-analysis.

Liao Calwing C Castonguay Charles-Etienne CE Heilbron Karl K Vuokila Veikko V Medeiros Miranda M Houle Gabrielle G Akçimen Fulya F Ross Jay P JP Catoire Helene H Diez-Fairen Monica M Kang Jooeun J Mueller Stefanie H SH Girard Simon L SL Hopfner Franziska F Lorenz Delia D Clark Lorraine N LN Soto-Beasley Alexandra I AI Klebe Stephan S Hallett Mark M Wszolek Zbigniew K ZK Pendziwiat Manuela M Lorenzo-Betancor Oswaldo O Seppi Klaus K Berg Daniela D Vilariño-Güell Carles C Postuma Ronald B RB Bernard Geneviève G Dupré Nicolas N Jankovic Joseph J Testa Claudia M CM Ross Owen A OA Arzberger Thomas T Chouinard Sylvain S Louis Elan D ED Mandich Paola P Vitale Carmine C Barone Paolo P García-Martín Elena E Alonso-Navarro Hortensia H Agúndez José A G JAG Jiménez-Jiménez Félix Javier FJ Pastor Pau P Rajput Alex A Deuschl Günther G Kuhlenbaümer Gregor G Meijer Inge A IA Dion Patrick A PA Rouleau Guy A GA

JAMA neurology 20220201 2

<h4>Importance</h4>Essential tremor (ET) is one of the most common movement disorders, affecting 5% of the general population older than 65 years. Common variants are thought to contribute toward susceptibility to ET, but no variants have been robustly identified.<h4>Objective</h4>To identify common genetic factors associated with risk of ET.<h4>Design, setting, and participants</h4>Case-control genome-wide association study. Inverse-variance meta-analysis was used to combine cohorts. Multicente ...[more]

PMID: 34982113

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Project description:ObjectiveJuvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease and has a strong genomic component. To date, JIA genetic association studies have had limited sample sizes, used heterogeneous patient populations, or included only candidate regions. The aim of this study was to identify new associations between JIA patients with oligoarticular disease and those with IgM rheumatoid factor (RF)-negative polyarticular disease, which are clinically similar and the most prevalent JIA disease subtypes.MethodsThree cohorts comprising 2,751 patients with oligoarticular or RF-negative polyarticular JIA were genotyped using the Affymetrix Genome-Wide SNP Array 6.0 or the Illumina HumanCoreExome-12+ Array. Overall, 15,886 local and out-of-study controls, typed on these platforms or the Illumina HumanOmni2.5, were used for association analyses. High-quality single-nucleotide polymorphisms (SNPs) were used for imputation to 1000 Genomes prior to SNP association analysis.ResultsMeta-analysis showed evidence of association (P < 1 × 10-6 ) at 9 regions: PRR9_LOR (P = 5.12 × 10-8 ), ILDR1_CD86 (P = 6.73 × 10-8 ), WDFY4 (P = 1.79 × 10-7 ), PTH1R (P = 1.87 × 10-7 ), RNF215 (P = 3.09 × 10-7 ), AHI1_LINC00271 (P = 3.48 × 10-7 ), JAK1 (P = 4.18 × 10-7 ), LINC00951 (P = 5.80 × 10-7 ), and HBP1 (P = 7.29 × 10-7 ). Of these, PRR9_LOR, ILDR1_CD86, RNF215, LINC00951, and HBP1 were shown, for the first time, to be autoimmune disease susceptibility loci. Furthermore, associated SNPs included cis expression quantitative trait loci for WDFY4, CCDC12, MTP18, SF3A1, AHI1, COG5, HBP1, and GPR22.ConclusionThis study provides evidence of both unique JIA risk loci and risk loci overlapping between JIA and other autoimmune diseases. These newly associated SNPs are shown to influence gene expression, and their bounding regions tie into molecular pathways of immunologic relevance. Thus, they likely represent regions that contribute to the pathology of oligoarticular JIA and RF-negative polyarticular JIA.

Dataset Information

Association of Essential Tremor With Novel Risk Loci: A Genome-Wide Association Study and Meta-analysis.

Importance

Objective

Design, setting, and participants

Main outcomes and measures

Results

Conclusions and relevance

Publications

Association of Essential Tremor With Novel Risk Loci: A Genome-Wide Association Study and Meta-analysis.

Similar Datasets

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