The few loci associated with multiple sclerosis (MS) are all related to immune function. We report a GWA study identifying a new locus replicated in 2,679 cases and 3,125 controls. An rs10492972[C] variant located in the KIF1B gene was associated with MS with an odds ratio of 1.35 (P = 2.5 x 10(-10)). KIF1B is a neuronally expressed gene plausibly implicated in the irreversible axonal loss characterizing MS in the long term.

HLA-DRB1 is the major locus associated with risk for multiple sclerosis (MS). A recent genome-wide study showed three additional single-nucleotide polymorphisms (SNPs), within the IL2RA and IL7RA genes respectively, also to be associated with MS. Consistent association but lower significance was found for 13 other SNPs. In this study, we aimed to verify association of these SNPs with MS in 46 MS patients and 194 controls from a Dutch genetically isolated population. Apart from the human leukocyte antigen locus, the EVI5 gene on chromosome 1 was confirmed as a novel risk gene, with odds ratios (ORs) even higher than those from the MS Consortium (ORs 2.01 and 1.9; P ¼ 0.01). The risk effect of EVI5 was further validated for the general MS population in an independent set of 1318 MS patients from the Canadian Collaborative Project on the Genetic Susceptibility to MS. On the basis of the transmission disequilibrium testing, a weak but significant risk effect was observed (OR 1.15; P ¼ 0.03 and OR 1.15; P ¼ 0.04). This study confirms EVI5 as another risk locus for MS; however, much of the genetic basis of MS remains unidentified.

Description Functions for simple fixed and random effects meta-analysis for two-sample comparisons and cumulative meta-analyses. Draws standard summary plots, funnel plots, and computes summaries and tests for association and heterogeneity.Title Meta-AnalysisLicense GPL-2Imports grid, stats, graphics Examples library(rmeta) data(catheter) a <-meta.MH(n.trt, n.ctrl, col.trt, col.ctrl, data=catheter, names=Name, subset=c (13,6,5,3,7,12,4,11,1,8,10,2)) b <-meta.DSL(n.trt, n.ctrl, col.trt, col.ctrl, data=catheter, names=Name,subset=c (13,6,5,3,7,12,4,11,1,8,10,2)) a b summary(a) summary ( DetailsThis meta-analysis, if done, would likely have resulted in the treatment being widely used a decade earlier than it was, saving many lives. The graph is part of the logo of the Cochrane Collaboration, a group aiming to perform systematic reviews of the entire clinical trial literature. Cumulative meta-analysis of binary data DescriptionA cumulative meta-analysis plot shows how evidence has accumulated over time. The ith line in the cumulative meta-analysis plot is the summary produced by a meta-analysis of the first i trials.Usage cummeta(ntrt, nctrl, ptrt, pctrl, conf.level = 0.95, names = NULL, data= NULL, subset = NULL, na.action = na.fail, method = c("meta.MH", "meta.DSL"), statistic = "OR") cummeta.summaries(effects,stderrs, conf.level = 0.95, names = NULL,weights=NULL, data= NULL, subset = NULL, na.action = get(getOption("na.action")), method = c("fixed", "random"), logscale=TRUE) ## S3 method for class meta.cum plot(x, conf.level = NULL, colors = meta.colors(), xlab = NULL, summary.line = TRUE, summary.conf = FALSE, main="Cumulative meta-analysis", lwd=1, ...) ## S3 method for class meta.cum summary (object ,conf.level=NULL,...)