No association of the SLC1A2 rs3794087 allele with risk for essential tremor in the Spanish population

García‐Martín, Elena; Martı́nez, Carmen; Alonso‐Navarro, Hortensia; Benito‐León, Julián; Lorenzo‐Betancor, Oswaldo; Pástor, Pau; Ortega‐Cubero, Sara; López-Alburquerque, Tomás; Agúndez, José A. G.; Jiménez‐Jiménez, Félix Javier

doi:10.1097/fpc.0b013e328364db9d

Cited by 22 publications

(11 citation statements)

References 18 publications

(28 reference statements)

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“…To date, four studies have attempted to replicate the association of rs3794087 with ET in different populations, with conflicting results, some of which are positive (Chinese, Taiwanese) and others of which are negative (Spanish, North American) (Garcia-Martin et al, 2013; Tan et al, 2013; Ross et al, 2014). While further studies in different populations are needed to confirm the role of SLC1A2 in ET, rs3794087 is unlikely to represent a major risk factor for ET.…”

Section: Modes Of Inheritance and Transmission In Essential Tremormentioning

confidence: 99%

Essential tremor

Clark

Louis

2018

Handbook of Clinical Neurology

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Essential tremor (ET) is one of the most common neurologic disorders, and genetic factors are thought to contribute significantly to disease etiology. There has been a relative lack of progress in understanding the genetic etiology of ET. This could reflect a number of factors, including the presence of substantial phenotypic and genotypic heterogeneity. Thus, a meticulous approach to phenotyping is important for genetic research. A lack of standardized phenotyping across studies and patient centers likely has contributed to the relative lack of success of genomewide association studies in ET. To dissect the genetic architecture of ET, whole-genome sequencing will likely be of value. This will allow specific hypotheses about the mode of inheritance and genetic architecture to be tested. A number of approaches still remain unexplored in ET genetics, including the contribution of copy number variants, uncommon moderate-effect alleles, rare variant large-effect alleles (including Mendelian and complex/polygenic modes of inheritance), de novo and gonadal mosaicism, epigenetic changes, and noncoding variation.

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Section: Modes Of Inheritance and Transmission In Essential Tremormentioning

confidence: 99%

Essential tremor

Clark

Louis

2018

Handbook of Clinical Neurology

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“…However, even when using multi-component approaches, heritability is likely underestimated. We believe that these estimates Many studies have failed to consistently unravel and replicate strong GWAS associated signals in ET (37)(38)(39)(40)(41), which suggests that ET is genetically very complex in nature and as other diseases, might not be driven by a single locus but rather by many loci with very small effect sizes that cumulatively increase disease risk. In that way, we provided data showing the contribution of 294 intervals of 10Mb size across the genome to the overall heritability.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide estimates of heritability and genetic correlations in Essential Tremor

Díez-Fairén

Bandrés‐Ciga

Houle

et al. 2019

Preprint

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Despite considerable efforts to identify disease-causing and risk factors contributing to essential tremor (ET), no comprehensive assessment of heritable risk has been performed to date. We use GREML-LDMS to estimate narrow-sense heritability due to additive effects (h 2 ) and GREMLd to calculate non-additive heritability due to dominance variance (δ 2 ) using data from 1,748 ET cases and 5,302 controls. We evaluate heritability per 10Mb segments across the genome and assess the impact of Parkinson's disease (PD) misdiagnosis on heritability estimates. We apply genetic risk score (GRS) from PD and restless legs syndrome (RLS) to explore its contribution to ET risk and further assess genetic correlations with 832 traits by Linkage disequilibrium score regression. Our results show for the first time that ET is a highly heritable condition (h 2 =0.755, s.e=0.075) in which additive common variability plays a prominent role. In contrast, dominance variance shows insignificant effect on the overall estimates. Heritability split by 10Mb regions revealed increased estimates at chromosomes 6 and 21 suggesting that these may contain causative risk variants influencing susceptibility to ET. The proportion of genetic variance due to PD misdiagnosed cases was estimated to be 5.33%. PD and RLS GRS were not significantly predictive of ET case-control status demonstrating that despite overlapping symptomatology, ET does not seem to share genetic etiologies with PD or RLS. Our study suggests that most of ET genetic component is yet to be discovered and future GWAS will reveal additional risk factors that will improve our understanding of this disabling disorder.

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“…Recruitment was done at the Movement Disorders of three University Hospitals. Most of them participated in previous case–control association studies reported by our group .…”

Section: Methodsmentioning

confidence: 99%

“…Genotyping of the ALAD rs1800435 polymorphism was carried out using a TaqMan genotyping assay (C__11495146_10; Applied Biosciences Hispania, Alcobendas, Madrid, Spain). The procedure is identical to that described elsewhere with the only difference of the genotyping assay used. Genotyping method and results of HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363 and HMOX2 rs1051308 were described elsewhere .…”

Section: Methodsmentioning

confidence: 99%