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Modifiers described so far have been tested mainly for associations with ambulatory function, while their effect on upper limb function, which is especially relevant for quality of life and independence in non-ambulatory patients, is unknown. We tested genotypes at several known modifier loci (<jats:italic>SPP1<\/jats:italic>, <jats:italic>LTBP4<\/jats:italic>, <jats:italic>CD40<\/jats:italic>, <jats:italic>ACTN3<\/jats:italic>) for association with Performance Upper Limb version 1.2 score in an Italian multicenter cohort, and with Brooke scale score in the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS), using generalized estimating equation (GEE) models of longitudinally collected data, with age and glucocorticoid treatment as covariates. <jats:italic>CD40<\/jats:italic> rs1883832, previously linked to earlier loss of ambulation, emerged as a modifier of upper limb function, negatively affecting shoulder and distal domains of PUL (<jats:italic>p<\/jats:italic>\u2009=\u20090.023 and 0.018, respectively) in the Italian cohort, as well as of Brooke score (<jats:italic>p<\/jats:italic>\u2009=\u20090.018) in the CINRG-DNHS. These findings will be useful for the design and interpretation of clinical trials in DMD, especially for non-ambulatory populations.<\/jats:p>","DOI":"10.1007\/s00415-022-11133-8","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T20:08:02Z","timestamp":1651781282000},"page":"4884-4894","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genetic modifiers of upper limb function in Duchenne muscular 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