{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:59:50Z","timestamp":1777388390041,"version":"3.51.4"},"reference-count":25,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Multiple sclerosis (MS) is a complex disease of the central nervous system for which human leukocyte antigen (HLA) alleles are major contributors to susceptibility. Several investigations have focused on the relationship between HLA and clinical parameters, while few studies have evaluated its correlation with brain magnetic resonance imaging (MRI) measures. We investigated the association between the HLA genetic burden (HLAGB), originating from the most updated HLA alleles associated with MS, and neuroimaging endophenotypes, with a specific focus on brain atrophy metrics. A monocentric Italian cohort of 334 MS patients with imputed HLA alleles and cross-sectional volumetric measures of white matter (WM), gray matter (GM), hippocampus, thalamus and T2-hyperintense lesions was investigated. Linear regression models with covariate adjustment were fitted for each metric. We detected no effect of HLAGB on WM and GM volumes. Interestingly, we found a marginal correlation between higher HLAGB and lower hippocampal volume (\u03b2 = \u22120.142, p = 0.063) and a nominal association between higher HLAGB and lower thalamic volume (\u03b2 = \u22120.299, p = 0.047). No association was found with T2 lesion volumes. The putative impact of higher HLAGB on hippocampus and thalamus suggests, if replicated in independent cohorts, a possible cumulative contribution of HLA risk loci on brain volumetric traits linked to clinical deficits in MS.<\/jats:p>","DOI":"10.3390\/genes13112136","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T03:24:34Z","timestamp":1668655474000},"page":"2136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exploring the Association of HLA Genetic Risk Burden on Thalamic and Hippocampal Atrophy in Multiple Sclerosis Patients"],"prefix":"10.3390","volume":"13","author":[{"given":"Silvia","family":"Santoro","sequence":"first","affiliation":[{"name":"Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdinando","family":"Clarelli","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7826-0019","authenticated-orcid":false,"given":"Paolo","family":"Preziosa","sequence":"additional","affiliation":[{"name":"Unit of Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4979-613X","authenticated-orcid":false,"given":"Loredana","family":"Storelli","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miryam","family":"Cannizzaro","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Unit of Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Mascia","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Esposito","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Unit of Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Assunta","family":"Rocca","sequence":"additional","affiliation":[{"name":"Unit of Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Filippi","sequence":"additional","affiliation":[{"name":"Unit of Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Neurophysiology Service, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1399-0039.1985.tb00436.x","article-title":"HLA and multiple sclerosis: Population and families study","volume":"25","author":"Govaerts","year":"1985","journal-title":"Tissue Antigens"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Patsopoulos, N., Barcellos, L.F., Hintzen, R.Q., Schaefer, C., Van Duijn, C.M., Noble, J.A., Raj, T., Gourraud, P.-A., Stranger, B., and Oksenberg, J. 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