In-silico analysis of inflammatory bowel disease (IBD) GWAS loci to novel connections

PloS One
Md Mesbah-UddinFahad A Al-Abbasi

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 classifi...Continue Reading

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Jan 7, 2017·Journal of Cellular Biochemistry·Babajan BanaganapalliRamu Elango
Nov 9, 2016·PloS One·Wing-Cheong LoAvner Friedman
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Feb 9, 2020·Genetics, Selection, Evolution : GSE·Christian GroßDick de Ridder

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Software Mentioned

dbPSHP webserver
GeneMANIA
CADD
RegulomeDB
GWAVA
HaploReg
R
ENCODE
Genomic Evolutionary Rate Profiling ( GERP + + )
MCODE

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