Network-based multiple sclerosis pathway analysis with GWAS data from 15,000 cases and 30,000 controls

摘要: Multiple sclerosis (MS) is an inflammatory CNS disease with a substantial genetic component, originally mapped to only the human leukocyte antigen (HLA) region. In last 5 years, total of seven genome-wide association studies and one meta-analysis successfully identified 57 non-HLA susceptibility loci. Here, we merged nominal statistical evidence physical interaction conduct protein-interaction-network-based pathway analysis (PINBPA) on two large MS comprising 15,317 cases 29,529 controls. The distribution nominally significant loci at gene level matched patterns extended linkage disequilibrium in regions interest. We found that products significantly associated genes are more likely interact physically belong same or related pathways. next searched for subnetworks (modules) (and their encoded proteins) enriched within each study those modules common between studies. demonstrate these contain bona fide variants and, addition, identify several high-confidence candidates (including BCL10, CD48, REL, TRAF3, TEC). PINBPA powerful approach gaining further insights into biology prioritizing subsequent complex traits.