0000000000281996
AUTHOR
Denis A. Akkad
Genome-wide significant association of ANKRD55 rs6859219 and multiple sclerosis risk.
Multiple sclerosis (MS) is a genetically complex disease that shares a substantial proportion of risk loci with other autoimmune diseases.1 Along these lines, ANKRD55 , originally implicated in rheumatoid arthritis, was recently reported as a potential novel MS risk gene (rs6859219, p=1.9×10−7).2 Here, we comprehensively validated this effect in independent datasets comprising 8846 newly genotyped subjects from Germany and France as well as 5003 subjects from two genome-wide association studies (GWAS). Upon meta-analysis of all available data (19 686 subjects), ANKRD55 rs6859219 now shows compelling evidence for association with MS at genome-wide significance (OR=1.19, p=3.1×10−11). Our stu…
Genome-wide significant association with seven novel multiple sclerosis risk loci
Objective A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. Methods The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Results…
Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients.
Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, lin…