title: Inverse correlation of genetic risk score with age at onset in bout-onset and progressive-onset multiple sclerosis.
abstract: We correlated the weighted genetic risk score measured using 107 established susceptibility variants for multiple sclerosis (MS) with the age at onset in bout-onset (BOMS, n=906) and progressive-onset MS Italian patients (PrMS) (n=544). We observed an opposite relationship in the two disease courses: a higher weighted genetic risk score was associated with an earlier age at onset in BOMS (rho= -0.1; p=5 × 10(-3)) and a later age at onset in PrMS cases (rho=0.07; p=0.15) (p of difference of regression=1.4 × 10(-2)). These findings suggest that established MS risk variants anticipate the onset of the inflammatory phase, while they have no impact on, or even delay, the onset of the progressive phase.
authors.affiliation: Laboratory of Genetics of Neurological complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Melissa
authors.initials: M
authors.lastname: Sorosina
authors.affiliation: Laboratory of Genetics of Neurological complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy/Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Esposito
authors.affiliation: Laboratory of Genetics of Neurological complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy/Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Guaschino
authors.affiliation: Laboratory of Genetics of Neurological complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Clarelli
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Disease IRCAD, University of Eastern Piedmont, Novara, Italy/Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Barizzone
authors.affiliation: Laboratory of Genetics of Neurological complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Osiceanu
authors.affiliation: Laboratory of Genetics of Neurological complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Brambilla
authors.affiliation: Laboratory of Genetics of Neurological complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Mascia
authors.affiliation: Multiple Sclerosis Centre, AOUS Giovanni Battista di Torino, Department of Neurosciences, University of Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cavalla
authors.affiliation: The Multiple Sclerosis Centre of Veneto Region, First Neurology Clinic, Department of Neurosciences, University Hospital of Padova, Padua, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gallo
authors.affiliation: Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Martinelli
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Disease IRCAD, University of Eastern Piedmont, Novara, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Leone
authors.affiliation: Laboratory of Genetics of Neurological complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy/Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Interdisciplinary Research Centre of Autoimmune Disease IRCAD, University of Eastern Piedmont, Novara, Italy/Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.affiliation: Laboratory of Genetics of Neurological complex Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy/Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy martinelli.filippo@hsr.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Martinelli Boneschi
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000453:epidemiology / Q000503:physiopathology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000453:epidemiology / Q000503:physiopathology*; D012306:Risk; D055815:Young Adult
keywords: Primary-progressive; age of onset; genetic risk; multiple sclerosis; relapsing–remitting; weighted genetic risk score