Genome-Wide Association Study in an Admixed Case Series Reveals IL12A as a New Candidate in Behçet Disease

• DOI: 10.1371/journal.pone.0119085
• Publication Date: 2015-03-23T18:23:00Z
• Authors: Jasper H. Kappen; Carolina Medina-G...; P. Martin van Hagen; Lisette Stolk; Karol Estrada; Fernando Rivadeneira; Andre G. Uitterli...; Miles R. Stanford; Eldat Ben-Chetrit; Graham R. Wallace; Merih Soylu; Jan A.M. van Laar
• Keywords: Genome-wide Association Study

Introduction The etiology of Behçet's disease (BD) is unknown, but widely considered an excessive T-cell mediated inflammatory response in a genetically susceptible host. Recent genome-wide association studies (GWAS) have shown limited number novel loci-associations. rarity and unequal distribution the prevalence amongst different ethnic backgrounds hampered use GWAS cohorts mixed ethnicity sufficient sample size. However, statistical approaches now enabled admixed cohorts. Methods We ran on 336 BD cases 5,843 controls. consisted Western Europeans, Middle Eastern Turkish individuals. Participants from Generation R study, multiethnic birth cohort Rotterdam, Netherlands were used as All samples genotyped data was combined. Linear regression models corrected for population stratification using Genomic Principal Components Mixed Modelling. Meta-analysis performed selected results previously published. Results identified SNPs associated at significant level mapping to 6p21.33 (HLA) region. In addition this known signal two potential associations chromosomes 6 18 identified, yet with low minor allele frequencies. Extended meta-analysis reveal GWS IL12A variant rs17810546 chromosome 3. Discussion demonstrate that new techniques enable analyses sized ethnicity. After implementation, we confirmed central role HLA region regions interest. Moreover, validated IL2A gene by previous work. These findings enhance our knowledge genetic BD, provide further justification pursuing collective initiatives given other rare diseases.