Genome-wide estimates of heritability and genetic correlations in Essential Tremor
Sara Bandres Ciga,
Mike A Nalls,
Simon L Girard,
Patrick A Dion,
Andrew B. Singleton,
Guy A. Rouleau,
Posted 19 Feb 2019
bioRxiv DOI: 10.1101/555235 (published DOI: 10.1016/j.parkreldis.2019.05.002)
Posted 19 Feb 2019
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 (h2) and GREMLd to calculate non-additive heritability due to dominance variance 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 (h2=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.
- Downloaded 384 times
- Download rankings, all-time:
- Site-wide: 86,476
- In genetics: 3,704
- Year to date:
- Site-wide: 145,242
- Since beginning of last month:
- Site-wide: 123,452
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!