title: In-silico analysis of inflammatory bowel disease (IBD) GWAS loci to novel connections.
abstract: Genome-wide association studies (GWASs) for many complex diseases, including inflammatory bowel disease (IBD), produced hundreds of disease-associated loci-the majority of which are noncoding. The number of GWAS loci is increasing very rapidly, but the process of translating single nucleotide polymorphisms (SNPs) from these loci to genomic medicine is lagging. In this study, we investigated 4,734 variants from 152 IBD associated GWAS loci (IBD associated 152 lead noncoding SNPs identified from pooled GWAS results + 4,582 variants in strong linkage-disequilibrium (LD) (r2 ≥0.8) for EUR population of 1K Genomes Project) using four publicly available bioinformatics tools, e.g. dbPSHP, CADD, GWAVA, and RegulomeDB, to annotate and prioritize putative regulatory variants. Of the 152 lead noncoding SNPs, around 11% are under strong negative selection (GERP++ RS ≥2); and ~30% are under balancing selection (Tajima's D score >2) in CEU population (1K Genomes Project)--though these regions are positively selected (GERP++ RS <0) in mammalian evolution. The analysis of 4,734 variants using three integrative annotation tools produced 929 putative functional SNPs, of which 18 SNPs (from 15 GWAS loci) are in concordance with all three classifiers. These prioritized noncoding SNPs may contribute to IBD pathogenesis by dysregulating the expression of nearby genes. This study showed the usefulness of integrative annotation for prioritizing fewer functional variants from a large number of GWAS markers.
authors.affiliation: Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Md
authors.initials: M
authors.lastname: Mesbah-Uddin
authors.affiliation: Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ramu
authors.initials: R
authors.lastname: Elango
authors.affiliation: Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Babajan
authors.initials: B
authors.lastname: Banaganapalli
authors.affiliation: Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Noor Ahmad
authors.initials: NA
authors.lastname: Shaik
authors.affiliation: Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Fahad A
authors.initials: FA
authors.lastname: Al-Abbasi
mesh_terms: D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D044465:White People / Q000235:genetics