Shared genetic architecture between Alzheimer's disease and psychiatric disorders revealed by multi-trait genome-wide analyses.
Overview
- Neurosurgery Department, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi China
- Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
Abstract
Objective: Clarify the shared genetic architecture between Alzheimer’s disease (AD) and major psychiatric disorders.
Methods: We integrated large GWAS summary datasets derived predominantly from individuals of European ancestry for AD and eight psychiatric disorders; estimated genome-wide genetic correlations with LDSC/
Results: HDL identified significant genome-wide correlations for five AD–psychiatric pairs, led by AD–MDD; LDSC was significant for AD–MDD. We mapped 18 locally correlated regions. MTAG yielded 33 AD-associated loci (118 SNPs), including 12 novel (e.g., RAB27B/
Conclusion: AD shares substantial pleiotropic architecture with psychiatric disorders, particularly MDD. Integrative multi-trait association, colocalization, and tissue-specific eQTL evidence highlights convergent mechanisms—exosome biology (RAB27B), astrocytic Ca²⁺ signaling (P4HTM), and non-amyloidogenic APP processing (ADAM10)—and nominates testable therapeutic targets.
Supplementary Information: The online version contains supplementary material available at 10.1186/
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Datasets cited
- figshare:32672100, at figshare; found in DataCite
Data availability
Processed result tables generated in this study are available from the corresponding author on reasonable request.
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 5 keywords, 7 MeSH terms, 60 references.
Cite
This paper
Zhang, H., Xie, L., Meng, F., Cui, J., Ma, B., Wang, Y., Zhang, K., & Miao, X. (2026). Shared genetic architecture between Alzheimer's disease and psychiatric disorders revealed by multi-trait genome-wide analyses. BMC medical genomics, 19(1), 100. https://
BibTeX
@article{zhang2026shared
author = {Zhang, Huajun and Xie, Liangzhuo and Meng, Facai and Cui, Jiangli and Ma, Bo and Wang, Yu and Zhang, Kai and Miao, Xingyu},
title = {{Shared genetic architecture between Alzheimer's disease and psychiatric disorders revealed by multi-trait genome-wide analyses}},
journal = {BMC medical genomics},
year = {2026},
month = apr,
volume = {19},
number = {1},
pages = {100},
publisher = {BMC},
issn = {1755-8794},
doi = {10.1186/
url = {https://
pmid = {42050540},
pmcid = {PMC13267596}
}
RIS
TY - JOUR
AU - Zhang, Huajun
AU - Xie, Liangzhuo
AU - Meng, Facai
AU - Cui, Jiangli
AU - Ma, Bo
AU - Wang, Yu
AU - Zhang, Kai
AU - Miao, Xingyu
TI - Shared genetic architecture between Alzheimer's disease and psychiatric disorders revealed by multi-trait genome-wide analyses
T2 - BMC medical genomics
J2 - BMC Med Genomics
PY - 2026
DA - 2026/
VL - 19
IS - 1
SP - 100
SN - 1755-8794
PB - BMC
DO - 10.1186/
UR - https://
LA - en
ER -
CSL-JSON
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