Evidence map›Paper›PMID 40596977›Full record

ArticleBMC neurology2025

Integrated genetic analysis of Alzheimer's disease and stroke subtypes: insights from LDSC, PLACO, and MR studies.

Yu Long, Jinfeng Liu, Jinniu Guo, Jinzhao Jiang, Xiangyu Wang, Ruohan Sun

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Article in BMC neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

6 authors.

Yu LongDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, China.
Jinfeng LiuDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, China.
Jinniu GuoDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, China.
Jinzhao JiangDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, China.
Xiangyu WangDepartment of Ultrasound, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, China.
Ruohan SunDepartment of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, China. ruohan.sun@hrbmu.edu.cn.

Funding

Chunhui Program-Cooperative Research Project of the Ministry of Education HZKY20220315（202201826）Innovation Fund for Stem Cell Clinical Research Filing Institutions of the First Affiliated Hospital of Harbin Medical University 2023CX04Outstanding Medical Fund for Young Scholar of the First Affiliated Hospital of Harbin Medical University 2024JQ22 and 2024JQ19the National Natural Science Foundation of China 82001131 and 82002644
6 · The paper itself

Abstract

purposeThis study aimed to evaluate the genetic relationship between Alzheimer's disease (AD) and stroke, including its subtypes.

methodsThe Linkage Disequilibrium Score Regression (LDSC) for heritability and genetic correlations, Polygenic Likelihood Ratio under a Composite Null Hypothesis (PLACO) method for pleiotropic loci and locus, and Functional maps and annotations from genome-wide association studies (FUMA) for function analysis of multi-effect loci, multi-marker analysis of genoMic annotation (MAGMA) for gene tissue specificity, Mendelian Randomization (MR) analyses for causal relationships between AD and five stroke subtypes were performed through Single Nucleotide Polymorphism (SNP) heritability enrichments and causal associations were analyzed using comprehensive GWAS data.

resultsManhattan plots revealed pleiotropic SNPs mainly on chromosomes 11 and 19, with additional loci on chromosomes 1, 2, and 3 for specific subgroups. Key genes like DEDD, UFC1, USP21, affecting both AD and stroke subtypes, were enriched in brain tissues, highlighting shared mechanisms. Stratified LD score regression showed overlaps in brain regions such as substantia nigra and spinal cord. MR analysis indicated AD as a risk factor for LAS and AS but protective for cerebral embolism stroke (CES), supported by consistent causal effect estimates without publication bias. This study reveals that AD shares genetic factors with multiple stroke subtypes, notably in brain tissues, impacting their etiology and potential treatments.

conclusionOverall, our study revealed that AD shares genetic factors with multiple stroke subtypes, notably in brain tissues. MR analysis indicates AD is a risk factor for LAS and AS, but protective for CES.

Indexed as

Alzheimer DiseaseLinkage DisequilibriumStrokeGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMendelian Randomization AnalysisPolymorphism, Single NucleotideAlzheimer's diseaseGenetic correlationMendelian randomizationSingle Nucleotide Polymorphism (SNP)Stroke subtype

Identifiers

PMID40596977
PMCPMC12211776

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