Objective Genome structural equation modeling(GSEM)was used to study the shared genetic structure between Alzheimer's disease(AD)and eight cardiovascular diseases(CVD).Methods In this study,based on AD and CVD data from large consortia and genome-wide association studies,we used chained unbalanced score regression to assess the genetic correlation between the diseases;GSEM was introduced to cross-validate with exploratory factor analysis at odd chromosomes and validation factor analysis at even chromosomes,and pathway analysis was combined to establish three-factor,cofactor,and bifactorial models,so as to reveal the complex genetic relationships between the diseases.Additionally,a cross-validation was performed by swapping the positions of odd and even chromosomes.Results The nine selected diseases can be explained by a three-factor model consisting of three independent factors;a cofactor model explains the relationship between a cofactor and each disease;and an extended two-factor model(a combination of the three-factor model and the cofactor model)performs best in fitting the study data.Conclusion GSEM can be used to explore the shared genetic structure between AD and CVD to discover their interactions,laying a methodological foundation for understanding the genetic relationship between complex diseases.

Objective Genome structural equation modeling(GSEM)was used to study the shared genetic structure between Alzheimer's disease(AD)and eight cardiovascular diseases(CVD).Methods In this study,based on AD and CVD data from large consortia and genome-wide association studies,we used chained unbalanced score regression to assess the genetic correlation between the diseases;GSEM was introduced to cross-validate with exploratory factor analysis at odd chromosomes and validation factor analysis at even chromosomes,and pathway analysis was combined to establish three-factor,cofactor,and bifactorial models,so as to reveal the complex genetic relationships between the diseases.Additionally,a cross-validation was performed by swapping the positions of odd and even chromosomes.Results The nine selected diseases can be explained by a three-factor model consisting of three independent factors;a cofactor model explains the relationship between a cofactor and each disease;and an extended two-factor model(a combination of the three-factor model and the cofactor model)performs best in fitting the study data.Conclusion GSEM can be used to explore the shared genetic structure between AD and CVD to discover their interactions,laying a methodological foundation for understanding the genetic relationship between complex diseases.