AUTHOR=Step Kathryn , Leal Thiago Peixoto , Kamel Walaa A. , Waldo Emily , Bardien Soraya , Mata Ignacio F. 

TITLE=X chromosome-wide association studies in neurological disorders: uncovering the hidden influence of the X chromosome

JOURNAL=Frontiers in Genetics

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2025.1650259

DOI=10.3389/fgene.2025.1650259

ISSN=1664-8021

ABSTRACT=X chromosome-wide association studies (XWAS) have identified susceptibility variants for various neurodegenerative and neurodevelopmental diseases. The unique characteristics of the chromosome require more complex analytical approaches than standard genome-wide association studies. Over the past 2 decades, refined XWAS methods have better accounted for this biology. Given that many neurological diseases show sex-biased prevalence, XWAS offers a valuable framework for investigating sex-specific genetic contributions. This review summarizes published neurological XWAS (N = 10), highlighting methodological approaches. Despite the challenges of genetic analyses for the X chromosome, XWAS remains a key approach for studying its role in disease mechanisms.