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Abstract #1503

X Chromosome Genetic Overlap of Hormone, Lipid, and Brain Imaging Traits with Alzheimer’s Disease Reveals Novel Risk Genes

Noah Cook1, Chenyu Yang1, Danielle Reid1, and Michael Belloy1
1Washington University, Saint Louis, MO, United States

Synopsis

Keywords: Alzheimer's Disease, Genetics

Motivation: The X chromosome represents 5% of the genome and plays an obvious role in driving sex dimorphism yet has remained largely understudied in genome-wide association studies.

Goal(s): Leverage a recent large-scale X chromosome-wide association study of Alzheimer’s disease to integrate X chromosome genetic data from AD-related traits, including lipid, hormone, and brain imaging phenotypes, to identify shared genetic signals.

Approach: Genetic colocalization analyses across AD-trait pairs.

Results: We identified 20 loci with potential links to AD, including 15 novel risk loci, some showing female-specific effects. The findings enhance our understanding of sex-specific AD pathways and may inform future drug targets and treatment strategies.

Impact: Integrating X chromosome genetic data for Alzheimer’s disease (AD) with related traits, we uncovered 20 AD risk loci, including several showing sex-specific effects. These findings provide new biological insights into AD and highlight potential sex-agnostic and sex-specific AD drug targets.

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