MANBA, CXCR5, SOX8, RPS6KB1 and ZBTB46 are genetic risk loci for multiple sclerosis

Research output: Contribution to journalArticle

Abstract

A recent genome-wide association study reported five loci for which there was strong, but sub-genome-wide significant evidence for association with multiple sclerosis risk. The aim of this study was to evaluate the role of these potential risk loci in a large and independent data set of ≈ 20,000 subjects. We tested five single nucleotide polymorphisms rs228614 (MANBA), rs630923 (CXCR5), rs2744148 (SOX8), rs180515 (RPS6KB1), and rs6062314 (ZBTB46) for association with multiple sclerosis risk in a total of 8499 cases with multiple sclerosis, 8765 unrelated control subjects and 958 trios of European descent. In addition, we assessed the overall evidence for association by combining these newly generated data with the results from the original genome-wide association study by meta-analysis. All five tested single nucleotide polymorphisms showed consistent and statistically significant evidence for association with multiple sclerosis in our validation data sets (rs228614: odds ratio = 0.91, P = 2.4 × 10(-6); rs630923: odds ratio = 0.89, P = 1.2 × 10(-4); rs2744148: odds ratio = 1.14, P = 1.8 × 10(-6); rs180515: odds ratio = 1.12, P = 5.2 × 10(-7); rs6062314: odds ratio = 0.90, P = 4.3 × 10(-3)). Combining our data with results from the previous genome-wide association study by meta-analysis, the evidence for association was strengthened further, surpassing the threshold for genome-wide significance (P < 5 × 10(-8)) in each case. Our study provides compelling evidence that these five loci are genuine multiple sclerosis susceptibility loci. These results may eventually lead to a better understanding of the underlying disease pathophysiology.

Details

Authors
External organisations
  • University of the Basque Country
  • Max Planck Institute for Molecular Genetics
  • University of Mainz
  • University of Cambridge
  • CSIC Institute of Parasitology and Biomedicine Lopez-Neyra (IPBLN)
  • Hospital Clinico San Carlos de Madrid
  • Vall d'Hebron University Hospital
  • Pitié-Salpêtrière University Hospital
  • University of Sydney
  • Erasmus University Medical Center
  • University of Rostock
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics

Keywords

  • Case-Control Studies, Databases, Genetic, Female, Genetic Loci/genetics, Genetic Predisposition to Disease/genetics, Humans, Male, Multiple Sclerosis/diagnosis, Polymorphism, Single Nucleotide/genetics, Receptors, CXCR5/genetics, Ribosomal Protein S6 Kinases, 70-kDa/genetics, SOXE Transcription Factors/genetics, Transcription Factors/genetics, alpha-Mannosidase/genetics
Original languageEnglish
Pages (from-to)1778-82
Number of pages5
JournalBrain : a journal of neurology
Volume136
Issue numberPt 6
Publication statusPublished - 2013 Jun
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes