Cardiovascular disease contributes to Alzheimer's disease: evidence from large-scale genome-wide association studies.
Alzheimer's disease (AD) is the most common and complex neurodegenerative disease in the elderly individuals. Recently, genome-wide association studies (GWAS) have been used to investigate AD pathogenesis. These GWAS have yielded important new insights into the genetic mechanisms of AD. However, these newly identified AD susceptibility loci exert only very small risk effects and cannot fully explain the underlying AD genetic risk. We hypothesize that combining the findings from different AD GWAS may have greater power than genetic analysis alone. To identify new AD risk factors, we integrated findings from 3 previous large-scale AD GWAS (n = 14,138) using a gene-based meta-analysis and subsequently conducted a pathway analysis using the kyoto encyclopedia of genes and genomes and gene ontology databases. Interestingly, we not only confirmed previous findings, but also highlighted, for the first time, the involvement of cardiovascular disease-related pathways in AD. Our results provided the clues as to the link between these diseases using pathway analysis methods. We believe that these findings will be very useful for future genetic studies of AD.
Institute of Neurology, Guangdong Medical College, Zhanjiang, China; Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China. Electronic address: liuguiyou1981@163.com.
Guiyou
G
Liu
Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
Lifen
L
Yao
Department of Neurology, The First Hospital of Harbin, Harbin, Heilongjiang, China.
Jiafeng
J
Liu
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.
Yongshuai
Y
Jiang
Institute of Neurology, Guangdong Medical College, Zhanjiang, China.
Guoda
G
Ma
Department of Human Genetics, University of California at Los Angeles, Los Angeles, CA, USA.
Zugen
Z
Chen
Key laboratory of aging-related Cardio-cerebral diseases of Guangdong Province, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
Bin
B
Zhao
Institute of Neurology, Guangdong Medical College, Zhanjiang, China; Key laboratory of aging-related Cardio-cerebral diseases of Guangdong Province, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China. Electronic address: keshenli2012@163.com.
Keshen
K
Li
D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000150:complications*; D030541:Databases, Genetic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D015201:Meta-Analysis as Topic; D012306:Risk; D012307:Risk Factors
Alzheimer's disease; Cardiovascular disease; Genome-wide association studies; Pathway analysis