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Employing a genome-wide association study to identify additional factors modifying age at onset, we establish that three independent loci are significantly associated with age at onset (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20095\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    ). The lead single nucleotide polymorphisms collectively account for 25.6% of the remaining variance not explained by the hexanucleotide repeat and 13.0% of the overall variance in age at onset in X-linked dystonia-parkinsonism with the protective alleles delaying disease onset by seven years. These regions harbor or lie adjacent to\n                    <jats:italic>MSH3<\/jats:italic>\n                    and\n                    <jats:italic>PMS2<\/jats:italic>\n                    , the genes that were recently implicated in modifying age at onset in Huntington\u2019s disease, likely through a common pathway influencing repeat instability. Our work indicates the existence of three modifiers of age at onset in X-linked dystonia-parkinsonism that likely affect the DNA mismatch repair pathway.\n                  <\/jats:p>","DOI":"10.1038\/s41467-021-23491-4","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T06:20:17Z","timestamp":1622182817000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Identifying genetic modifiers of age-associated penetrance in X-linked 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