No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis

An Goris, Jessica van Setten, Frank Diekstra, Stephan Ripke, Nikolaos A. Patsopoulos, Stephen J. Sawcer, Michael van Es, Peter M. Andersen, Judith Melki, Vincent Meininger, Orla Hardiman, John E. Landers, Robert H. Brown, Aleksey Shatunov, Nigel Leigh, Ammar Al-Chalabi, Christopher E. Shaw, Bryan J. Traynor, Adriano Chió, Gabriella RestagnoGabriele Mora, Roel A. Ophoff, Jorge R. Oksenberg, Philip Van Damme, Alastair Compston, Wim Robberecht, Bénédicte Dubois, Leonard H. van den Berg, Philip L. De Jager, Jan H. Veldink, Paul I W de Bakker

Research output: Contribution to journalArticle

Abstract

Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within individuals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control individuals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed.We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility betweenMSand ALS. Hence, our findings do not support a shared genetic background ofcommonrisk variants in MS and ALS.

Original languageEnglish
Pages (from-to)1916-1922
Number of pages7
JournalHuman Molecular Genetics
Volume23
Issue number7
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology
  • Medicine(all)

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    Goris, A., van Setten, J., Diekstra, F., Ripke, S., Patsopoulos, N. A., Sawcer, S. J., van Es, M., Andersen, P. M., Melki, J., Meininger, V., Hardiman, O., Landers, J. E., Brown, R. H., Shatunov, A., Leigh, N., Al-Chalabi, A., Shaw, C. E., Traynor, B. J., Chió, A., ... de Bakker, P. I. W. (2013). No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis. Human Molecular Genetics, 23(7), 1916-1922. https://doi.org/10.1093/hmg/ddt574