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The present study aimed to assess whether patients\u2019 sex, in the context of mutated and normal allele length, contributes to age on onset (AO) of HD. The study population comprised a large cohort of 3723 HD patients from the European Huntington\u2019s Disease Network\u2019s REGISTRY database collected at 160 sites across 17 European countries and in one location outside Europe. The data were analyzed using regression models and factorial analysis of variance (ANOVA) considering both mutated allele length and sex as predictors of patients\u2019 AO. AO, as described by the rater\u2019s estimate, was found to be later in affected women than in men across the whole population. This difference was most pronounced in a subgroup of 1273 patients with relatively short variants of the mutated allele (40\u201345 CAG repeats) and normal alleles in a higher half of length distribution\u2014namely, more than 17 CAG repeats; however, it was also observed in each group. Our results presented in this observational study point to sex-related differences in AO, most pronounced in the presence of the short mutated and long normal allele, which may add to understanding the dynamics of AO in Huntington\u2019s Disease.<\/jats:p><jats:p><jats:bold>Trial registration<\/jats:bold>: <jats:italic>ClinicalTrials.gov identifier<\/jats:italic> NCT01590589.<\/jats:p>","DOI":"10.1038\/s41598-024-64105-5","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T16:02:38Z","timestamp":1720454558000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sex contribution to average age at onset of Huntington\u2019s disease depends on the number of (CAG)n repeats"],"prefix":"10.1038","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct01590589","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Anna","family":"Stanis\u0142awska-Sachadyn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Krzemi\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zielonka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Krygier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Zi\u0119tkiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"S\u0142awek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janusz","family":"Limon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"REGISTRY investigators of the European Huntington\u2019s Disease Network (EHDN)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"64105_CR1","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.1002\/mds.29228","volume":"37","author":"A Medina","year":"2022","unstructured":"Medina, A., Mahjoub, Y., Shaver, L. & Pringsheim, T. 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