Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

By Ashley H Beecham, N. Patsopoulos, Dionysia K. Xifara, Mary F. Davis, A. Kemppinen, C. Cotsapas, T. Shah, Chris C. A. Spencer, David N. Booth, An Goris and 183 more. Nature Genetics, 2013

1,073 citations recorded by the source corpus.

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10−4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10−8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.

Subfields: Genetics, Pathology and Forensic Medicine, Rheumatology

View Paper: https://www.semanticscholar.org/paper/ab0c207925efaf7f53dd3e8601655847e73bee98

Citations in the corpus

• Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells (2016, neutral): “…al., 2010], inflammatory bowel disease [IBD] [Liu et al., 2015], including Crohn’s disease [CD] and ulcerative colitis [UC], multiple sclerosis [MS] [Beecham et al., 2013], type 1 diabetes [T1D] [Onengut-Gumuscu et al., 2015], and rheumatoid arthritis [RA] [Okada et al., 2014]), for which we…”
• Fine-mapping inflammatory bowel disease loci to single variant resolution (2017, neutral): “combination with the highest joint marginal likelihood (equation (8) in Supplementary Methods).”
• Multiple Sclerosis Genomic Map implicates peripheral immune cells & microglia in susceptibility (2019, neutral): “Second, we incorporated targeted genotyping data generated using the ImmunoChip platform on an additional 12,267 MS subjects and 22,625 control subjects that had not been used in either the discovery or the MS Chip subject sets (table S5) (3).”