https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:13695 1. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals^2,3, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk⁴. Modestly powered genome-wide association studies (GWAS)^5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility¹¹. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.]]> Sat 24 Mar 2018 08:19:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:12845 T at 3p24.1 (odds ratio [OR], 1.17; p = 1.6 × 10⁻⁸) near EOMES, rs2150702^G in the second intron of MLANA on chromosome 9p24.1 (OR, 1.16; p = 3.3 × 10⁻⁸), and rs6718520^A in an intergenic region on chromosome 2p21, with THADA as the nearest flanking gene (OR, 1.17; p = 3.4 × 10⁻⁸). The 3 new loci do not have a strong cis effect on RNA expression in PBMCs. Ten other susceptibility loci had a suggestive p < 1 × 10⁻⁶, some of these loci have evidence of association in other inflammatory diseases (ie, IL12B, TAGAP, PLEK, and ZMIZ1). Interpretation: We have performed a meta-analysis of GWAS in MS that more than doubles the size of previous gene discovery efforts and highlights 3 novel MS susceptibility loci. These and additional loci with suggestive evidence of association are excellent candidates for further investigations to refine and validate their role in the genetic architecture of MS.]]> Sat 24 Mar 2018 08:17:22 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10938 Sat 24 Mar 2018 08:13:21 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17125 −10) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes.]]> Sat 24 Mar 2018 08:02:31 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23143 Sat 24 Mar 2018 07:10:33 AEDT ]]>