Association of Essential Tremor With Novel Risk Loci

Liao, Calwing; Castonguay, Charles-Etienne; Heilbron, Karl; Vuokila, Veikko; Medeiros, Miranda; Houle, Gabrielle; Akçimen, Fulya; Ross, Jay P.; Catoire, Hélène; Díez-Fairén, Mónica; Kang, Jooeun; Mueller, Stefanie H.; Girard, Simon; Hopfner, Franziska; Lorenz, Delia; Clark, Lorraine N.; Soto-Beasley, Alexandra I.; Klebe, Stephan; Hallett, Mark; Wszołek, Zbigniew K.; Pendziwiat, Manuela; Lorenzo‐Betancor, Oswaldo; Seppi, Klaus; Berg, Daniela; Vilariño‐Güell, Carles; Postuma, Ronald B.; Bernard, Geneviève; Dupré, Nicolas; Jankovic, Joseph; Testa, Claudia; Ross, Owen A.; Arzberger, Thomas; Chouinard, Sylvain; Louis, Elan D.; Mandich, Paola; Barone, Paolo; García‐Martín, Elena; Alonso‐Navarro, Hortensia; Agúndez, José A. G.; Jiménez‐Jiménez, Félix Javier; Pástor, Pau; Rajput, Alex; Deuschl, G.; Kuhlenbäumer, Gregor; Meijer, Inge A.; Rouleau, Guy A.

doi:10.1001/jamaneurol.2021.4781

Cited by 24 publications

(15 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most patients with a history of drinking experienced an improvement in their tremors with alcohol consumption, and there was no significant difference between ET plus and ET patients. Genetics plays a significant role in the pathogenesis of ET [ 42 , 43 ]. However, the prevalence of positive family history was not significantly different between the groups in the current study.…”

Section: Discussionmentioning

confidence: 99%

Age and Sex Affect Essential Tremor (ET) Plus: Clinical Heterogeneity in ET Based on the National Survey in China

Sun¹,

He²,

Huang³

et al. 2022

Aging and disease

View full text Add to dashboard Cite

The new term essential tremor (ET) plus was proposed in the 2018 tremor consensus criteria. The National Survey of Essential Tremor Plus in China, a large multicenter registry study, aimed to evaluate the clinical features of pure ET and ET plus and explore possible factors related to ET plus. All patients with ET underwent neurological examination and neuropsychological assessment at 17 clinical sites. The diagnosis was made according to the 2018 consensus criteria. Clinicodemographic characteristics were analyzed. A total of 1160 patients were included, including 546 patients with pure ET and 614 patients with ET plus. The proportion of females was significantly higher in the ET plus than that in the pure ET (P = 0.001). The age at onset (AAO) of Early access date: December 11, 2022 Sun Q., et al.Age and sex affect ET plus Aging and Disease • 2 pure ET showed a bimodal distribution, with peaks in the 2nd and 5th decades. However, the AAO of the ET plus group demonstrated a skewed distribution, with a single peak in the 6th decade. Female sex (OR=1.645, P<0.001), older age (OR=1.023, P<0.001), lower educational level (OR=0.934, P<0.001), head tremor (OR=1.457, P<0.001), and higher the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS)-II scores (OR=1.134, P<0.001) were significantly associated with ET plus. Old age and female sex may contribute to ET plus development. Pure ET showed a bimodal distribution for AAO, whereas ET plus showed a unimodal distribution. It remains unclear whether pure ET and ET plus are merely different stages of a single disease or represent distinct disease entities.

show abstract

Section: Discussionmentioning

confidence: 99%

Age and Sex Affect Essential Tremor (ET) Plus: Clinical Heterogeneity in ET Based on the National Survey in China

Sun¹,

He²,

Huang³

et al. 2022

Aging and disease

View full text Add to dashboard Cite

show abstract

“…8 17 92 A recent genome-wide association study identified genes such as BACE2 , LRRN2 , DHRS13 , and LINC00323 in disease-relevant brain regions, such as the cerebellum. 93 It has then been hypothesized that some cases of ET, and more specifically “ET-plus,” are not associated with classical genetic mechanisms but rather with expansion triplet inheritance mechanisms. 8 In support of this hypothesis, trinucleotide (GGC repeats in NOTCH2NLC gene) and tetra/pentanucleotide repeat disorders (ATTTC repeats in STARD7 gene) have been shown as clearly pathogenic in patients who would clinically be diagnosed with “ET-plus,” and bilateral hand tremor associated with leukoencephalopathy and/or epilepsy.…”

Section: Ancillary Investigationsmentioning

confidence: 99%

“…8 Patients with genetic dystonias may have tremor as a part of their phenotypic presentation. 8,[92][93][94] Based on clinical and imaging features accompanying tremor (such as leukoencephalopathy, epilepsy, or dystonia), genetic testing may be helpful for diagnosis. However, at this point, the utility of genetic testing to identify a monogenic cause of tremor is limited and not recommended.…”

Section: Role Of Neuroimagingmentioning

confidence: 99%

Diagnostic Uncertainties in Tremor

2023

View full text Add to dashboard Cite

The approach and diagnosis of patients with tremor may be challenging for clinicians. According to the most recent consensus statement by the Task Force on Tremor of the International Parkinson Movement Disorder Society, the differentiation between action (i.e., kinetic, postural, intention), resting, and other task- and position-specific tremors is crucial to this goal. In addition, patients with tremor must be carefully examined for other relevant features, including the topography of the tremor, since it can involve different body areas and possibly associate with neurological signs of uncertain significance. Following the characterization of major clinical features, it may be useful to define, whenever possible, a particular tremor syndrome and to narrow down the spectrum of possible etiologies. First, it is important to distinguish between physiological and pathological tremor, and, in the latter case, to differentiate between the underlying pathological conditions. A correct approach to tremor is particularly relevant for appropriate referral, counseling, prognosis definition, and therapeutic management of patients. The purpose of this review is to outline the possible diagnostic uncertainties that may be encountered in clinical practice in the approach to patients with tremor. In addition to an emphasis on a clinical approach, this review discusses the important ancillary role of neurophysiology and innovative technologies, neuroimaging, and genetics in the diagnostic process.

show abstract

“…Evidence from genetic research suggested that LINGO1, LINGO2, HS1BP3, DNAJC13, HTRA2, NAACP-Rep1, and CACNA1G were overlapping genetic risks between them [13]. A recent published genome-wide association study (GWAS) of ET revealed significant common variant overlap with PD [14]. Our previous study systematically investigated the association between rare coding variants in ET-associated genes and EOPD, and found the suggestive association between teneurin transmembrane protein 4 (TENM4) and EOPD, which provided evidence for a genetic link between ET and PD [15].…”

Section: Introductionmentioning

confidence: 99%

Association Analysis of Essential Tremor-Associated Genetic Variants in Sporadic Late-Onset Parkinson’s Disease

Zeng,

Zhou,

et al. 2024

Tremor and Other Hyperkinetic Movements

View full text Add to dashboard Cite

Background: Parkinson's disease (PD) and Essential tremor (ET) are the two most common tremor diseases with recognized genetic pathogenesis. The overlapping clinical features suggest they may share genetic predispositions. Our previous study systematically investigated the association between rare coding variants in ET-associated genes and earlyonset PD (EOPD), and found the suggestive association between teneurin transmembrane protein 4 (TENM4) and EOPD. In the current research, we explored the potential genetic interplay between ET-associated genetic loci/genes and sporadic late-onset PD (LOPD). Methods:We performed whole-genome sequencing in the 1962 sporadic LOPD cases and 1279 controls from mainland China. We first used logistic regression analysis to test the top 16 SNPs identified by the ET genome-wide association study for the association between ET and LOPD. Then we applied the optimized sequence kernel association testing to explore the rare variant burden of 33 ET-associated genes in this cohort. Results:We did not observe a significant association between the included SNPs with LOPD. We also did not discover a significant burden of rare deleterious variants of ETassociated genes in association with LOPD risk. Conclusion:Our results do not support the role of ET-associated genetic loci and variants in LOPD. Highlights1. 1962 cases and 1279 controls were recruited to study the potential genetic interplay between ET-associated genetic loci/variants and sporadic LOPD. 2. No significant association between the ET-associated SNPs and LOPD were observed. 3. No significant burden of rare deleterious variants of ET-associated gene in LOPD risk were found.

show abstract

Association of Essential Tremor With Novel Risk Loci

Cited by 24 publications

References 69 publications

Age and Sex Affect Essential Tremor (ET) Plus: Clinical Heterogeneity in ET Based on the National Survey in China

Age and Sex Affect Essential Tremor (ET) Plus: Clinical Heterogeneity in ET Based on the National Survey in China

Diagnostic Uncertainties in Tremor

Association Analysis of Essential Tremor-Associated Genetic Variants in Sporadic Late-Onset Parkinson’s Disease

Contact Info

Product

Resources

About