AUTHOR=Wang Kai-Wen , Yuan Yu-Xin , Zhu Bin , Zhang Yi , Wei Yi-Fang , Meng Fan-Shuo , Zhang Shun , Wang Jing-Xuan , Zhou Ji-Yuan ,  for the Alzheimer’s Disease Neuroimaging Initiative 

TITLE=X chromosome-wide association study of quantitative biomarkers from the Alzheimer’s Disease Neuroimaging Initiative study

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=15

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1277731

DOI=10.3389/fnagi.2023.1277731

ISSN=1663-4365

ABSTRACT=<sec id="sec1"><title>Introduction</title><p>Alzheimer’s disease (AD) is a complex neurodegenerative disease with high heritability. Compared to autosomes, a higher proportion of disorder-associated genes on X chromosome are expressed in the brain. However, only a few studies focused on the identification of the susceptibility loci for AD on X chromosome.</p></sec><sec id="sec2"><title>Methods</title><p>Using the data from the Alzheimer’s Disease Neuroimaging Initiative Study, we conducted an X chromosome-wide association study between 16 AD quantitative biomarkers and 19,692 single nucleotide polymorphisms (SNPs) based on both the cross-sectional and longitudinal studies.</p></sec><sec id="sec3"><title>Results</title><p>We identified 15 SNPs statistically significantly associated with different quantitative biomarkers of the AD. For the cross-sectional study, six SNPs (rs5927116, rs4596772, rs5929538, rs2213488, rs5920524, and rs5945306) are located in or near to six genes <italic>DMD</italic>, <italic>TBX22</italic>, <italic>LOC101928437</italic>, <italic>TENM1</italic>, <italic>SPANXN1</italic>, and <italic>ZFP92</italic>, which have been reported to be associated with schizophrenia or neuropsychiatric diseases in literature. For the longitudinal study, four SNPs (rs4829868, rs5931111, rs6540385, and rs763320) are included in or near to two genes <italic>RAC1P4</italic> and <italic>AFF2</italic>, which have been demonstrated to be associated with brain development or intellectual disability in literature, while the functional annotations of other five novel SNPs (rs12157031, rs428303, rs5953487, rs10284107, and rs5955016) have not been found.</p></sec><sec id="sec4"><title>Discussion</title><p>15 SNPs were found statistically significantly associated with the quantitative biomarkers of the AD. Follow-up study in molecular genetics is needed to verify whether they are indeed related to AD. The findings in this article expand our understanding of the role of the X chromosome in exploring disease susceptibility, introduce new insights into the molecular genetics behind the AD, and may provide a mechanistic clue to further AD-related studies.</p></sec>