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

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

doi:10.3389/fnagi.2023.1277731

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

Front Aging Neurosci. 2023 Nov 14:15:1277731. doi: 10.3389/fnagi.2023.1277731. eCollection 2023.

Authors

Kai-Wen Wang^#^{1

2}, Yu-Xin Yuan^#^{1

2}, Bin Zhu^#^{1

2}, Yi Zhang^{1

2}, Yi-Fang Wei^{1

2}, Fan-Shuo Meng^{1

2}, Shun Zhang¹, Jing-Xuan Wang¹, Ji-Yuan Zhou^{1

2}; Alzheimer’s Disease Neuroimaging Initiative

Affiliations

¹ State Key Laboratory of Organ Failure Research, Ministry of Education, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, China.
² Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangzhou, China.

^# Contributed equally.

Abstract

Introduction: 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.

Methods: 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.

Results: 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 DMD, TBX22, LOC101928437, TENM1, SPANXN1, and ZFP92, 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 RAC1P4 and AFF2, 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.

Discussion: 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.

Keywords: Alzheimer’s disease; X chromosome-wide association study; cross-sectional study; longitudinal study; quantitative biomarker.

Grants and funding

U01 AG024904/AG/NIA NIH HHS/United States