{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:31:14Z","timestamp":1777937474118,"version":"3.51.4"},"reference-count":36,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T00:00:00Z","timestamp":1628640000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003000","name":"Stichting MS Research","doi-asserted-by":"publisher","award":["17-985 MS"],"award-info":[{"award-number":["17-985 MS"]}],"id":[{"id":"10.13039\/501100003000","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["91211021"],"award-info":[{"award-number":["91211021"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>MS patients show abnormalities in white matter (WM) on brain imaging, with heterogeneity in the location of WM lesions. The \u201cpothole\u201d method can be applied to diffusion-weighted images to identify spatially distinct clusters of divergent brain WM microstructure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To investigate the association between genetic risk for MS and spatially independent clusters of decreased or increased fractional anisotropy (FA) in the brain. In addition, we studied sex- and age-related differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>3 Tesla diffusion tensor imaging (DTI) data were collected in 8- to 12-year-old children from a population-based study. Global and tract-based potholes (lower FA clusters) and molehills (higher FA clusters) were quantified in 3047 participants with usable DTI data. A polygenic risk score (PRS) for MS was calculated in genotyped individuals ( n = 1087) and linear regression analyses assessed the relationship between the PRS and the number of potholes and molehills, correcting for multiple testing using the False Discovery Rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The number of molehills increased with age, potholes decreased with age, and fewer potholes were observed in girls during typical development. The MS-PRS was positively associated with the number of molehills (\u03b2 = 0.9, SE = 0.29, p = 0.002). Molehills were found more often in the corpus callosum (\u03b2 = 0.3, SE = 0.09, p = 0.0003).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Genetic risk for MS is associated with spatially distinct clusters of increased FA during childhood brain development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585211034826","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T09:08:18Z","timestamp":1628672898000},"page":"730-741","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["White matter microstructural differences in children and genetic risk for multiple sclerosis: A population-based study"],"prefix":"10.1177","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3733-1706","authenticated-orcid":false,"given":"C Louk","family":"de Mol","sequence":"first","affiliation":[{"name":"Department of Neurology, MS Center ErasMS, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands\/The Generation R Study Group, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rinze F","family":"Neuteboom","sequence":"additional","affiliation":[{"name":"Department of Neurology, MS Center ErasMS, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip R","family":"Jansen","sequence":"additional","affiliation":[{"name":"The Generation R Study Group, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands\/Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands\/Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tonya","family":"White","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"bibr1-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.011"},{"key":"bibr2-13524585211034826","volume":"365","author":"Consortium IMSG","year":"2019","journal-title":"Science"},{"key":"bibr3-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000436934.40034eb"},{"key":"bibr4-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70275-3"},{"key":"bibr5-13524585211034826","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.01165"},{"key":"bibr6-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25717"},{"key":"bibr7-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.148767"},{"key":"bibr8-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(96)05322-1"},{"key":"bibr9-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20767"},{"key":"bibr10-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1016\/j.pscychresns.2009.04.014"},{"key":"bibr11-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-017-0319-y"},{"key":"bibr12-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-013-9768-0"},{"key":"bibr13-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2017.16070813"},{"key":"bibr14-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.09.015"},{"key":"bibr15-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1016\/S1361-8415(01)00036-6"},{"key":"bibr16-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.21890"},{"key":"bibr17-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.10062"},{"key":"bibr18-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20426"},{"key":"bibr19-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.02.024"},{"key":"bibr20-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-374709-9.00008-0"},{"key":"bibr21-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.12.035"},{"key":"bibr22-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-015-9998-4"},{"key":"bibr23-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpsc.2018.07.010"},{"key":"bibr24-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1038\/nature02168"},{"key":"bibr25-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1021\/ci400128m"},{"key":"bibr26-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu848"},{"key":"bibr27-13524585211034826","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2009.05.004"},{"key":"bibr28-13524585211034826","unstructured":"Urbanek S, Bibiko H-J, Stefano ML. 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