PMID- 36421810 OWN - NLM STAT- MEDLINE DCOM- 20221129 LR - 20221208 IS - 2073-4425 (Electronic) IS - 2073-4425 (Linking) VI - 13 IP - 11 DP - 2022 Nov 17 TI - Exploring the Association of HLA Genetic Risk Burden on Thalamic and Hippocampal Atrophy in Multiple Sclerosis Patients. LID - 10.3390/genes13112136 [doi] LID - 2136 AB - 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 (beta = -0.142, p = 0.063) and a nominal association between higher HLAGB and lower thalamic volume (beta = -0.299, 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. FAU - Santoro, Silvia AU - Santoro S AD - Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. FAU - Clarelli, Ferdinando AU - Clarelli F AD - Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. FAU - Preziosa, Paolo AU - Preziosa P AUID- ORCID: 0000-0002-7826-0019 AD - Unit of Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. AD - Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. FAU - Storelli, Loredana AU - Storelli L AUID- ORCID: 0000-0002-4979-613X AD - Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. FAU - Cannizzaro, Miryam AU - Cannizzaro M AD - Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. AD - Unit of Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. FAU - Mascia, Elisabetta AU - Mascia E AD - Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. FAU - Esposito, Federica AU - Esposito F AD - Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. AD - Unit of Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. FAU - Rocca, Maria Assunta AU - Rocca MA AD - Unit of Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. AD - Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. AD - Vita-Salute San Raffaele University, 20132 Milan, Italy. FAU - Filippi, Massimo AU - Filippi M AD - Unit of Neurology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. AD - Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. AD - Vita-Salute San Raffaele University, 20132 Milan, Italy. AD - Neurophysiology Service, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. LA - eng PT - Journal Article DEP - 20221117 PL - Switzerland TA - Genes (Basel) JT - Genes JID - 101551097 RN - 0 (HLA Antigens) SB - IM MH - Humans MH - Atrophy/pathology MH - Cross-Sectional Studies MH - Hippocampus/diagnostic imaging/pathology MH - *Multiple Sclerosis/diagnostic imaging/genetics/pathology MH - Thalamus/diagnostic imaging/pathology MH - *HLA Antigens/genetics PMC - PMC9690825 OTO - NOTNLM OT - HLA OT - brain atrophy OT - genetic risk score OT - multiple sclerosis COIS- S.S., F.C., L.S., M.C. and E.M., have nothing to disclose. P.P. received speaker honoraria from Roche, Biogen, Novartis, Merck Serono, Bristol Myers Squibb and Genzyme. He has received research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. F.E. has received compensation for consulting services and/or speaking activities from Novartis, Sanofi Genzyme, Almirall and Merck-Serono. M.A.R. received speakers honoraria from Biogen Idec, Novartis, Genzyme, Teva, Merck Serono, Roche, Celgene and Bayer and receives research support from the MS Society of Canada and Fondazione Italiana Sclerosi Multipla. M.F. is the editor-in-chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, the Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla and ARiSLA (Fondazione Italiana di Ricerca per la SLA). EDAT- 2022/11/25 06:00 MHDA- 2022/11/29 06:00 PMCR- 2022/11/17 CRDT- 2022/11/24 09:58 PHST- 2022/10/19 00:00 [received] PHST- 2022/11/11 00:00 [revised] PHST- 2022/11/14 00:00 [accepted] PHST- 2022/11/24 09:58 [entrez] PHST- 2022/11/25 06:00 [pubmed] PHST- 2022/11/29 06:00 [medline] PHST- 2022/11/17 00:00 [pmc-release] AID - genes13112136 [pii] AID - genes-13-02136 [pii] AID - 10.3390/genes13112136 [doi] PST - epublish SO - Genes (Basel). 2022 Nov 17;13(11):2136. doi: 10.3390/genes13112136.