Polygenic Multiple Sclerosis Risk and Population-Based Childhood Brain Imaging.

Autor: de Mol CL; Generation R Study Group, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Neurology, MS Center ErasMS, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands., Jansen PR; Generation R Study Group, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Child and Adolescent Psychiatry, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Clinical Genetics, VU Medical Center, Amsterdam, the Netherlands., Muetzel RL; Generation R Study Group, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Child and Adolescent Psychiatry, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands., Knol MJ; Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands., Adams HH; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Clinical Genetics, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands., Jaddoe VW; Generation R Study Group, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Pediatrics, Sophia Children's Hospital, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands., Vernooij MW; Generation R Study Group, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands., Hintzen RQ; Department of Neurology, MS Center ErasMS, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands., White TJ; Department of Child and Adolescent Psychiatry, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands., Neuteboom RF; Department of Neurology, MS Center ErasMS, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.
Jazyk: angličtina
Zdroj: Annals of neurology [Ann Neurol] 2020 May; Vol. 87 (5), pp. 774-787. Date of Electronic Publication: 2020 Mar 27.
DOI: 10.1002/ana.25717
Abstrakt: Objective: Multiple sclerosis (MS) is a neurological disease with a substantial genetic component and immune-mediated neurodegeneration. Patients with MS show structural brain differences relative to individuals without MS, including smaller regional volumes and alterations in white matter (WM) microstructure. Whether genetic risk for MS is associated with brain structure during early neurodevelopment remains unclear. In this study, we explore the association between MS polygenic risk scores (PRS) and brain imaging outcomes from a large, population-based pediatric sample to gain insight into the underlying neurobiology of MS.
Methods: We included 8- to 12-year-old genotyped participants from the Generation R Study in whom T1-weighted volumetric (n = 1,136) and/or diffusion tensor imaging (n = 1,088) had been collected. PRS for MS were calculated based on a large genome-wide association study of MS (n = 41,505) and were regressed on regional volumes, global and tract-specific fractional anisotropy (FA), and global mean diffusivity using linear regression.
Results: No associations were observed for the regional volumes. We observed a positive association between the MS PRS and global FA (β = 0.098, standard error [SE] = 0.030, p = 1.08 × 10 -3 ). Tract-specific analyses showed higher FA and lower radial diffusivity in several tracts. We replicated our findings in an independent sample of children (n = 186) who were scanned in an earlier phase (global FA; β = 0.189, SE = 0.072, p = 9.40 × 10 -3 ).
Interpretation: This is the first study to show that greater genetic predisposition for MS is associated with higher global brain WM FA at an early age in the general population. Our results suggest a preadolescent time window within neurodevelopment in which MS risk variants act upon the brain. ANN NEUROL 2020;87:774-787.
(© 2020 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)
Databáze: MEDLINE
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