Literature DB >> 32864809

The Parkinson's Disease Genome-Wide Association Study Locus Browser.

Francis P Grenn1, Jonggeol J Kim1, Mary B Makarious1, Hirotaka Iwaki1,2, Anastasia Illarionova3, Kajsa Brolin4, Jillian H Kluss1, Artur F Schumacher-Schuh5, Hampton Leonard1,2, Faraz Faghri1,2, Kimberley Billingsley1, Lynne Krohn6, Ashley Hall7, Monica Diez-Fairen8, Maria Teresa Periñán9, Jia Nee Foo10,11, Cynthia Sandor12, Caleb Webber12, Brian K Fiske13, J Raphael Gibbs1, Mike A Nalls1,2, Andrew B Singleton1, Sara Bandres-Ciga1, Xylena Reed1, Cornelis Blauwendraat1.   

Abstract

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease with an often complex component identifiable by genome-wide association studies. The most recent large-scale PD genome-wide association studies have identified more than 90 independent risk variants for PD risk and progression across more than 80 genomic regions. One major challenge in current genomics is the identification of the causal gene(s) and variant(s) at each genome-wide association study locus. The objective of the current study was to create a tool that would display data for relevant PD risk loci and provide guidance with the prioritization of causal genes and potential mechanisms at each locus.
METHODS: We included all significant genome-wide signals from multiple recent PD genome-wide association studies including themost recent PD risk genome-wide association study, age-at-onset genome-wide association study, progression genome-wide association study, and Asian population PD risk genome-wide association study. We gathered data for all genes 1 Mb up and downstream of each variant to allow users to assess which gene(s) are most associated with the variant of interest based on a set of self-ranked criteria. Multiple databases were queried for each gene to collect additional causal data.
RESULTS: We created a PD genome-wide association study browser tool (https://pdgenetics.shinyapps.io/GWASBrowser/) to assist the PD research community with the prioritization of genes for follow-up functional studies to identify potential therapeutic targets.
CONCLUSIONS: Our PD genome-wide association study browser tool provides users with a useful method of identifying potential causal genes at all known PD risk loci from large-scale PD genome-wide association studies. We plan to update this tool with new relevant data as sample sizes increase and new PD risk loci are discovered.
© 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Entities:  

Keywords:  GWAS; Parkinson's disease; prioritization

Mesh:

Year:  2020        PMID: 32864809      PMCID: PMC7754106          DOI: 10.1002/mds.28197

Source DB:  PubMed          Journal:  Mov Disord        ISSN: 0885-3185            Impact factor:   9.698


  56 in total

1.  PLINK: a tool set for whole-genome association and population-based linkage analyses.

Authors:  Shaun Purcell; Benjamin Neale; Kathe Todd-Brown; Lori Thomas; Manuel A R Ferreira; David Bender; Julian Maller; Pamela Sklar; Paul I W de Bakker; Mark J Daly; Pak C Sham
Journal:  Am J Hum Genet       Date:  2007-07-25       Impact factor: 11.025

2.  The P2RY12 receptor promotes VSMC-derived foam cell formation by inhibiting autophagy in advanced atherosclerosis.

Authors:  Shulan Pi; Ling Mao; Jiefang Chen; Hanqing Shi; Yuxiao Liu; Xiaoqing Guo; Yuanyuan Li; Lian Zhou; Hui He; Cheng Yu; Jianyong Liu; Yiping Dang; Yuanpeng Xia; Quanwei He; Huijuan Jin; Yanan Li; Yu Hu; Yiliang Miao; Zhenyu Yue; Bo Hu
Journal:  Autophagy       Date:  2020-03-19       Impact factor: 16.016

3.  Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets.

Authors:  Zhihong Zhu; Futao Zhang; Han Hu; Andrew Bakshi; Matthew R Robinson; Joseph E Powell; Grant W Montgomery; Michael E Goddard; Naomi R Wray; Peter M Visscher; Jian Yang
Journal:  Nat Genet       Date:  2016-03-28       Impact factor: 38.330

4.  LocusZoom: regional visualization of genome-wide association scan results.

Authors:  Randall J Pruim; Ryan P Welch; Serena Sanna; Tanya M Teslovich; Peter S Chines; Terry P Gliedt; Michael Boehnke; Gonçalo R Abecasis; Cristen J Willer
Journal:  Bioinformatics       Date:  2010-07-15       Impact factor: 6.937

5.  The open targets post-GWAS analysis pipeline.

Authors:  Gareth Peat; William Jones; Michael Nuhn; José Carlos Marugán; William Newell; Ian Dunham; Daniel Zerbino
Journal:  Bioinformatics       Date:  2020-05-01       Impact factor: 6.937

6.  Functionalization of the TMEM175 p.M393T variant as a risk factor for Parkinson disease.

Authors:  Sarah Jinn; Cornelis Blauwendraat; Dawn Toolan; Cheryl A Gretzula; Robert E Drolet; Sean Smith; Mike A Nalls; Jacob Marcus; Andrew B Singleton; David J Stone
Journal:  Hum Mol Genet       Date:  2019-10-01       Impact factor: 6.150

7.  Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.

Authors:  Luke Jostins; Stephan Ripke; Rinse K Weersma; Richard H Duerr; Dermot P McGovern; Ken Y Hui; James C Lee; L Philip Schumm; Yashoda Sharma; Carl A Anderson; Jonah Essers; Mitja Mitrovic; Kaida Ning; Isabelle Cleynen; Emilie Theatre; Sarah L Spain; Soumya Raychaudhuri; Philippe Goyette; Zhi Wei; Clara Abraham; Jean-Paul Achkar; Tariq Ahmad; Leila Amininejad; Ashwin N Ananthakrishnan; Vibeke Andersen; Jane M Andrews; Leonard Baidoo; Tobias Balschun; Peter A Bampton; Alain Bitton; Gabrielle Boucher; Stephan Brand; Carsten Büning; Ariella Cohain; Sven Cichon; Mauro D'Amato; Dirk De Jong; Kathy L Devaney; Marla Dubinsky; Cathryn Edwards; David Ellinghaus; Lynnette R Ferguson; Denis Franchimont; Karin Fransen; Richard Gearry; Michel Georges; Christian Gieger; Jürgen Glas; Talin Haritunians; Ailsa Hart; Chris Hawkey; Matija Hedl; Xinli Hu; Tom H Karlsen; Limas Kupcinskas; Subra Kugathasan; Anna Latiano; Debby Laukens; Ian C Lawrance; Charlie W Lees; Edouard Louis; Gillian Mahy; John Mansfield; Angharad R Morgan; Craig Mowat; William Newman; Orazio Palmieri; Cyriel Y Ponsioen; Uros Potocnik; Natalie J Prescott; Miguel Regueiro; Jerome I Rotter; Richard K Russell; Jeremy D Sanderson; Miquel Sans; Jack Satsangi; Stefan Schreiber; Lisa A Simms; Jurgita Sventoraityte; Stephan R Targan; Kent D Taylor; Mark Tremelling; Hein W Verspaget; Martine De Vos; Cisca Wijmenga; David C Wilson; Juliane Winkelmann; Ramnik J Xavier; Sebastian Zeissig; Bin Zhang; Clarence K Zhang; Hongyu Zhao; Mark S Silverberg; Vito Annese; Hakon Hakonarson; Steven R Brant; Graham Radford-Smith; Christopher G Mathew; John D Rioux; Eric E Schadt; Mark J Daly; Andre Franke; Miles Parkes; Severine Vermeire; Jeffrey C Barrett; Judy H Cho
Journal:  Nature       Date:  2012-11-01       Impact factor: 49.962

8.  Penetrance of Parkinson's Disease in LRRK2 p.G2019S Carriers Is Modified by a Polygenic Risk Score.

Authors:  Hirotaka Iwaki; Cornelis Blauwendraat; Mary B Makarious; Sara Bandrés-Ciga; Hampton L Leonard; J Raphael Gibbs; Dena G Hernandez; Sonja W Scholz; Faraz Faghri; Mike A Nalls; Andrew B Singleton
Journal:  Mov Disord       Date:  2020-01-20       Impact factor: 9.698

9.  Regulation of microglial TMEM119 and P2RY12 immunoreactivity in multiple sclerosis white and grey matter lesions is dependent on their inflammatory environment.

Authors:  Thecla A van Wageningen; Eva Vlaar; Gijs Kooij; Cornelis A M Jongenelen; Jeroen J G Geurts; Anne-Marie van Dam
Journal:  Acta Neuropathol Commun       Date:  2019-12-11       Impact factor: 7.801

10.  Genetic modifiers of risk and age at onset in GBA associated Parkinson's disease and Lewy body dementia.

Authors:  Cornelis Blauwendraat; Xylena Reed; Lynne Krohn; Karl Heilbron; Sara Bandres-Ciga; Manuela Tan; J Raphael Gibbs; Dena G Hernandez; Ravindran Kumaran; Rebekah Langston; Luis Bonet-Ponce; Roy N Alcalay; Sharon Hassin-Baer; Lior Greenbaum; Hirotaka Iwaki; Hampton L Leonard; Francis P Grenn; Jennifer A Ruskey; Marya Sabir; Sarah Ahmed; Mary B Makarious; Lasse Pihlstrøm; Mathias Toft; Jacobus J van Hilten; Johan Marinus; Claudia Schulte; Kathrin Brockmann; Manu Sharma; Ari Siitonen; Kari Majamaa; Johanna Eerola-Rautio; Pentti J Tienari; Alexander Pantelyat; Argye E Hillis; Ted M Dawson; Liana S Rosenthal; Marilyn S Albert; Susan M Resnick; Luigi Ferrucci; Christopher M Morris; Olga Pletnikova; Juan Troncoso; Donald Grosset; Suzanne Lesage; Jean-Christophe Corvol; Alexis Brice; Alastair J Noyce; Eliezer Masliah; Nick Wood; John Hardy; Lisa M Shulman; Joseph Jankovic; Joshua M Shulman; Peter Heutink; Thomas Gasser; Paul Cannon; Sonja W Scholz; Huw Morris; Mark R Cookson; Mike A Nalls; Ziv Gan-Or; Andrew B Singleton
Journal:  Brain       Date:  2020-01-01       Impact factor: 13.501

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  22 in total

Review 1.  Brain Cell Type-Specific Nuclear Proteomics Is Imperative to Resolve Neurodegenerative Disease Mechanisms.

Authors:  Ruth S Nelson; Eric B Dammer; Juliet V Santiago; Nicholas T Seyfried; Srikant Rangaraju
Journal:  Front Neurosci       Date:  2022-06-16       Impact factor: 5.152

2.  Fine-mapping of Parkinson's disease susceptibility loci identifies putative causal variants.

Authors:  Brian M Schilder; Towfique Raj
Journal:  Hum Mol Genet       Date:  2022-03-21       Impact factor: 5.121

3.  Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies.

Authors:  Katia de Paiva Lopes; Gijsje J L Snijders; Jack Humphrey; Lot D de Witte; Towfique Raj; Amanda Allan; Marjolein A M Sneeboer; Elisa Navarro; Brian M Schilder; Ricardo A Vialle; Madison Parks; Roy Missall; Welmoed van Zuiden; Frederieke A J Gigase; Raphael Kübler; Amber Berdenis van Berlekom; Emily M Hicks; Chotima Bӧttcher; Josef Priller; René S Kahn
Journal:  Nat Genet       Date:  2022-01-06       Impact factor: 41.307

4.  Characterizing the Expression Patterns of Parkinson's Disease Associated Genes.

Authors:  Bin Li; Guihu Zhao; Kuokuo Li; Zheng Wang; Zhenghuan Fang; Xiaomeng Wang; Tengfei Luo; Yi Zhang; Yijing Wang; Qian Chen; Yuanfeng Huang; Lijie Dong; Jifeng Guo; Beisha Tang; Jinchen Li
Journal:  Front Neurosci       Date:  2021-04-01       Impact factor: 4.677

5.  Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease.

Authors:  Cornelis Blauwendraat; Hirotaka Iwaki; Mary B Makarious; Sara Bandres-Ciga; Hampton L Leonard; Francis P Grenn; Julie Lake; Lynne Krohn; Manuela Tan; Jonggeol J Kim; Jesse R Gibbs; Dena G Hernandez; Jennifer A Ruskey; Lasse Pihlstrøm; Mathias Toft; Jacobus J van Hilten; Johan Marinus; Claudia Schulte; Kathrin Brockmann; Manu Sharma; Ari Siitonen; Kari Majamaa; Johanna Eerola-Rautio; Pentti J Tienari; Donald G Grosset; Suzanne Lesage; Jean-Christophe Corvol; Alexis Brice; Nick Wood; John Hardy; Ziv Gan-Or; Peter Heutink; Thomas Gasser; Huw R Morris; Alastair J Noyce; Mike A Nalls; Andrew B Singleton
Journal:  Ann Neurol       Date:  2021-05-24       Impact factor: 11.274

Review 6.  Microglia in Neurodegenerative Events-An Initiator or a Significant Other?

Authors:  Gaylia Jean Harry
Journal:  Int J Mol Sci       Date:  2021-05-29       Impact factor: 5.923

Review 7.  Genetic Risk Profiling in Parkinson's Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological Pathways.

Authors:  Ashley Hall; Sara Bandres-Ciga; Monica Diez-Fairen; John P Quinn; Kimberley J Billingsley
Journal:  Int J Mol Sci       Date:  2020-10-04       Impact factor: 5.923

Review 8.  Advancing Personalized Medicine in Common Forms of Parkinson's Disease through Genetics: Current Therapeutics and the Future of Individualized Management.

Authors:  Xylena Reed; Artur Schumacher-Schuh; Jing Hu; Sara Bandres-Ciga
Journal:  J Pers Med       Date:  2021-03-01

Review 9.  The Genetics of Parkinson's Disease and Implications for Clinical Practice.

Authors:  Jacob Oliver Day; Stephen Mullin
Journal:  Genes (Basel)       Date:  2021-06-30       Impact factor: 4.096

10.  Machine Learning Identifies Six Genetic Variants and Alterations in the Heart Atrial Appendage as Key Contributors to PD Risk Predictivity.

Authors:  Daniel Ho; William Schierding; Sophie L Farrow; Antony A Cooper; Andreas W Kempa-Liehr; Justin M O'Sullivan
Journal:  Front Genet       Date:  2022-01-03       Impact factor: 4.599

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