title: Histone deacetylase gene variants predict brain volume changes in multiple sclerosis.
abstract: Neuroimaging measures hold promise for enhancing the detection of disease-related genetic variants. In this study, we use advanced multivariate regression methods to assess the predictive value of single nucleotide polymorphisms (SNPs) on several brain volumetric- and lesion-related neuroimaging measures in a well-characterized cohort of 326 patients with multiple sclerosis (MS). SNP selection was constrained to key epigenetic regulatory genes to further explore the emerging role of epigenetics in MS. Regression models consistently identified rs2522129, rs2675231, and rs2389963 as having among the highest predictive values for explaining differences related to brain volume measures. These SNPs are all contained in genes from the same superfamily, histone deacetylases, which have biological functions that are relevant to MS, neurodegeneration, and aging. Our preliminary findings generate hypotheses for testing in future independent MS data sets as well as other neurodegenerative conditions.
authors.affiliation: Department of Medicine, Centre for Neuroscience, Hammersmith Hospital, Imperial College London, London, UK. bi212@medschl.cam.ac.uk
authors.forename: Becky
authors.initials: B
authors.lastname: Inkster
authors.forename: Eva M M
authors.initials: EM
authors.lastname: Strijbis
authors.forename: Maria
authors.initials: M
authors.lastname: Vounou
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: Ernst-Wilhelm
authors.initials: EW
authors.lastname: Radue
authors.forename: Paul M
authors.initials: PM
authors.lastname: Matthews
authors.forename: Bernard M J
authors.initials: BM
authors.lastname: Uitdehaag
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Chris H
authors.initials: CH
authors.lastname: Polman
authors.forename: Giovanni
authors.initials: G
authors.lastname: Montana
authors.forename: Jeroen J G
authors.initials: JJ
authors.lastname: Geurts
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D012044:Regression Analysis; D055815:Young Adult
chemical_list: D006655:Histone Deacetylases