title: Identification of possible pathogenic pathways in Behçet's disease using genome-wide association study data from two different populations.
abstract: Behçet's disease (BD) is a multi-system inflammatory disorder of unknown etiology. Two recent genome-wide association studies (GWASs) of BD confirmed a strong association with the MHC class I region and identified two non-HLA common genetic variations. In complex diseases, multiple factors may target different sets of genes in the same pathway and thus may cause the same disease phenotype. We therefore hypothesized that identification of disease-associated pathways is critical to elucidate mechanisms underlying BD, and those pathways may be conserved within and across populations. To identify the disease-associated pathways, we developed a novel methodology that combines nominally significant evidence of genetic association with current knowledge of biochemical pathways, protein-protein interaction networks, and functional information of selected SNPs. Using this methodology, we searched for the disease-related pathways in two BD GWASs in Turkish and Japanese case-control groups. We found that 6 of the top 10 identified pathways in both populations were overlapping, even though there were few significantly conserved SNPs/genes within and between populations. The probability of random occurrence of such an event was 2.24E-39. These shared pathways were focal adhesion, MAPK signaling, TGF-β signaling, ECM-receptor interaction, complement and coagulation cascades, and proteasome pathways. Even though each individual has a unique combination of factors involved in their disease development, the targeted pathways are expected to be mostly the same. Hence, the identification of shared pathways between the Turkish and the Japanese patients using GWAS data may help further elucidate the inflammatory mechanisms in BD pathogenesis.
authors.affiliation: 1] Department of Genetics and Bioinformatics, Faculty of Arts and Sciences, Bahcesehir University, Istanbul, Turkey [2] Department of Computer Engineering, Faculty of Engineering and Natural Sciences, Abdullah Gul University, Kayseri, Turkey.
authors.forename: Burcu
authors.initials: B
authors.lastname: Bakir-Gungor
authors.affiliation: Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Remmers
authors.affiliation: Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Meguro
authors.affiliation: Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Mizuki
authors.affiliation: Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Kastner
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Gul
authors.affiliation: Biological Sciences and Bioengineering, Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.
authors.forename: Osman U
authors.initials: OU
authors.lastname: Sezerman
mesh_terms: D001528:Behcet Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D066264:Datasets as Topic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction; D014421:Turkey