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Despite its size, the role of X-chromosomal variants in human diseases is not well understood, mainly due to its distinct inheritance pattern and the frequent omission of sex chromosomes from genome-wide association studies.<\/jats:p>\n                  <jats:p>This study used whole-genome sequencing data from 888 multiple system atrophy (MSA) cases and 7128 controls to perform an X-chromosome-wide common variant association study. Our analyses revealed two sex-differential risk loci: one located at Xq28, associated with increased risk for MSA in females [index variant: rs4898389, odds ratio (OR) = 1.69, 95% confidence interval (CI) = 1.40\u20132.03, P-value = 2.43 \u00d7 10\u207b\u2078], and another at Xp22.2 within the TBL1X gene, identified in males (index variant: rs6638956, OR = 1.48, 95%CI = 1.26\u20131.73, P-value = 9.92 \u00d7 10\u207b\u2077). In the Xq28 locus, colocalization analyses pointed to FAM3A and PLXNA3 as genes of interest.<\/jats:p>\n                  <jats:p>These findings emphasize the vital role of sex-differential genetic factors in the pathogenesis of MSA.<\/jats:p>","DOI":"10.1093\/brain\/awag062","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:47:13Z","timestamp":1770900433000},"page":"3110-3118","source":"Crossref","is-referenced-by-count":2,"title":["Chromosome X-wide association study in multiple system atrophy identifies sex-differential risk loci"],"prefix":"10.1093","volume":"149","author":[{"given":"Anindita","family":"Ray","sequence":"first","affiliation":[{"name":"Neurodegenerative Diseases Research Section, National Institute of Neurological Disorders and Stroke , Bethesda, MD 20892 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