Vilija G Jokubaitis1,2,3, Yuan Zhou4, Helmut Butzkueven1,2,3,5, Bruce V Taylor6,7. 1. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia. 2. Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia. 3. Department of Neurology, Royal Melbourne Hospital, Parkville, Australia. 4. Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia. 5. Department of Neurology, Box Hill Hospital, Box Hill, Australia. 6. Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia. bruce.taylor@utas.edu.au. 7. Department of Neurology, Royal Hobart Hospital, Hobart, Australia. bruce.taylor@utas.edu.au.
Abstract
PURPOSE OF REVIEW: This review will examine the current evidence that genetic and/or epigenetic variation may influence the multiple sclerosis (MS) clinical course, phenotype, and measures of MS severity including disability progression and relapse rate. RECENT FINDINGS: There is little evidence that MS clinical phenotype is under significant genetic control. There is increasing evidence that there may be genetic determinants of the rate of disability progression. However, studies that can analyse disability progression and take into account all the confounding variables such as treatment, clinical characteristics, and environmental factors are by necessity longitudinal, relatively small, and generally of short duration, and thus do not lend themselves to the assessment of hundreds of thousands of genetic variables obtained from GWAS. Despite this, there is recent evidence to support the association of genetic loci with relapse rate. Recent progress suggests that genetic variations could be associated with disease severity, but not MS clinical phenotype, but these findings are not definitive and await replication. Pooling of study results, application of other genomic techniques including epigenomics, and analysis of biomarkers of progression could functionally validate putative severity markers.
PURPOSE OF REVIEW: This review will examine the current evidence that genetic and/or epigenetic variation may influence the multiple sclerosis (MS) clinical course, phenotype, and measures of MS severity including disability progression and relapse rate. RECENT FINDINGS: There is little evidence that MS clinical phenotype is under significant genetic control. There is increasing evidence that there may be genetic determinants of the rate of disability progression. However, studies that can analyse disability progression and take into account all the confounding variables such as treatment, clinical characteristics, and environmental factors are by necessity longitudinal, relatively small, and generally of short duration, and thus do not lend themselves to the assessment of hundreds of thousands of genetic variables obtained from GWAS. Despite this, there is recent evidence to support the association of genetic loci with relapse rate. Recent progress suggests that genetic variations could be associated with disease severity, but not MS clinical phenotype, but these findings are not definitive and await replication. Pooling of study results, application of other genomic techniques including epigenomics, and analysis of biomarkers of progression could functionally validate putative severity markers.
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Authors: Andreas P Lysandropoulos; Nicolas Mavroudakis; Massimo Pandolfo; Kaoutar El Hafsi; Wim van Hecke; Anke Maertens; Thibo Billiet; Annemie Ribbens Journal: J Neurol Sci Date: 2017-02-16 Impact factor: 3.181
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Authors: Jennifer S Graves; Lisa F Barcellos; Xiaorong Shao; Janelle Noble; Ellen M Mowry; Hong Quach; Anita Belman; T Charles Casper; Lauren B Krupp; Emmanuelle Waubant Journal: Mult Scler Date: 2016-01-14 Impact factor: 6.312
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Authors: Stephen Sawcer; Garrett Hellenthal; Matti Pirinen; Chris C A Spencer; Nikolaos A Patsopoulos; Loukas Moutsianas; Alexander Dilthey; Zhan Su; Colin Freeman; Sarah E Hunt; Sarah Edkins; Emma Gray; David R Booth; Simon C Potter; An Goris; Gavin Band; Annette Bang Oturai; Amy Strange; Janna Saarela; Céline Bellenguez; Bertrand Fontaine; Matthew Gillman; Bernhard Hemmer; Rhian Gwilliam; Frauke Zipp; Alagurevathi Jayakumar; Roland Martin; Stephen Leslie; Stanley Hawkins; Eleni Giannoulatou; Sandra D'alfonso; Hannah Blackburn; Filippo Martinelli Boneschi; Jennifer Liddle; Hanne F Harbo; Marc L Perez; Anne Spurkland; Matthew J Waller; Marcin P Mycko; Michelle Ricketts; Manuel Comabella; Naomi Hammond; Ingrid Kockum; Owen T McCann; Maria Ban; Pamela Whittaker; Anu Kemppinen; Paul Weston; Clive Hawkins; Sara Widaa; John Zajicek; Serge Dronov; Neil Robertson; Suzannah J Bumpstead; Lisa F Barcellos; Rathi Ravindrarajah; Roby Abraham; Lars Alfredsson; Kristin Ardlie; Cristin Aubin; Amie Baker; Katharine Baker; Sergio E Baranzini; Laura Bergamaschi; Roberto Bergamaschi; Allan Bernstein; Achim Berthele; Mike Boggild; Jonathan P Bradfield; David Brassat; Simon A Broadley; Dorothea Buck; Helmut Butzkueven; Ruggero Capra; William M Carroll; Paola Cavalla; Elisabeth G Celius; Sabine Cepok; Rosetta Chiavacci; Françoise Clerget-Darpoux; Katleen Clysters; Giancarlo Comi; Mark Cossburn; Isabelle Cournu-Rebeix; Mathew B Cox; Wendy Cozen; Bruce A C Cree; Anne H Cross; Daniele Cusi; Mark J Daly; Emma Davis; Paul I W de Bakker; Marc Debouverie; Marie Beatrice D'hooghe; Katherine Dixon; Rita Dobosi; Bénédicte Dubois; David Ellinghaus; Irina Elovaara; Federica Esposito; Claire Fontenille; Simon Foote; Andre Franke; Daniela Galimberti; Angelo Ghezzi; Joseph Glessner; Refujia Gomez; Olivier Gout; Colin Graham; Struan F A Grant; Franca Rosa Guerini; Hakon Hakonarson; Per Hall; Anders Hamsten; Hans-Peter Hartung; Rob N Heard; Simon Heath; Jeremy Hobart; Muna Hoshi; Carmen Infante-Duarte; Gillian Ingram; Wendy Ingram; Talat Islam; Maja Jagodic; Michael Kabesch; Allan G Kermode; Trevor J Kilpatrick; Cecilia Kim; Norman Klopp; Keijo Koivisto; Malin Larsson; Mark Lathrop; Jeannette S Lechner-Scott; Maurizio A Leone; Virpi Leppä; Ulrika Liljedahl; Izaura Lima Bomfim; Robin R Lincoln; Jenny Link; Jianjun Liu; Aslaug R Lorentzen; Sara Lupoli; Fabio Macciardi; Thomas Mack; Mark Marriott; Vittorio Martinelli; Deborah Mason; Jacob L McCauley; Frank Mentch; Inger-Lise Mero; Tania Mihalova; Xavier Montalban; John Mottershead; Kjell-Morten Myhr; Paola Naldi; William Ollier; Alison Page; Aarno Palotie; Jean Pelletier; Laura Piccio; Trevor Pickersgill; Fredrik Piehl; Susan Pobywajlo; Hong L Quach; Patricia P Ramsay; Mauri Reunanen; Richard Reynolds; John D Rioux; Mariaemma Rodegher; Sabine Roesner; Justin P Rubio; Ina-Maria Rückert; Marco Salvetti; Erika Salvi; Adam Santaniello; Catherine A Schaefer; Stefan Schreiber; Christian Schulze; Rodney J Scott; Finn Sellebjerg; Krzysztof W Selmaj; David Sexton; Ling Shen; Brigid Simms-Acuna; Sheila Skidmore; Patrick M A Sleiman; Cathrine Smestad; Per Soelberg Sørensen; Helle Bach Søndergaard; Jim Stankovich; Richard C Strange; Anna-Maija Sulonen; Emilie Sundqvist; Ann-Christine Syvänen; Francesca Taddeo; Bruce Taylor; Jenefer M Blackwell; Pentti Tienari; Elvira Bramon; Ayman Tourbah; Matthew A Brown; Ewa Tronczynska; Juan P Casas; Niall Tubridy; Aiden Corvin; Jane Vickery; Janusz Jankowski; Pablo Villoslada; Hugh S Markus; Kai Wang; Christopher G Mathew; James Wason; Colin N A Palmer; H-Erich Wichmann; Robert Plomin; Ernest Willoughby; Anna Rautanen; Juliane Winkelmann; Michael Wittig; Richard C Trembath; Jacqueline Yaouanq; Ananth C Viswanathan; Haitao Zhang; Nicholas W Wood; Rebecca Zuvich; Panos Deloukas; Cordelia Langford; Audrey Duncanson; Jorge R Oksenberg; Margaret A Pericak-Vance; Jonathan L Haines; Tomas Olsson; Jan Hillert; Adrian J Ivinson; Philip L De Jager; Leena Peltonen; Graeme J Stewart; David A Hafler; Stephen L Hauser; Gil McVean; Peter Donnelly; Alastair Compston Journal: Nature Date: 2011-08-10 Impact factor: 49.962
Authors: O G Kulakova; M R Kabilov; L V Danilova; E V Popova; O A Baturina; E Y Tsareva; N M Baulina; I S Kiselev; A N Boyko; A V Favorov; O O Favorova; V V Vlassov Journal: Acta Naturae Date: 2016 Jul-Sep Impact factor: 1.845