ANKRD55 and DHCR7 are novel multiple sclerosis risk loci

Research output: Contribution to journalArticle


Multiple sclerosis (MS) shares some risk genes with other disorders hallmarked by an autoimmune pathogenesis, most notably IL2RA and CLEC16A. We analyzed 10 single-nucleotide polymorphisms (SNPs) in nine risk genes, which recently emerged from a series of non-MS genome-wide association studies (GWAS), in a Spanish cohort comprising 2895 MS patients and 2942 controls. We identified two SNPs associated with MS. The first SNP, rs6859219, located in ANKRD55 (Chr5), was recently discovered in a meta-analysis of GWAS on rheumatoid arthritis (RA), and emerged from this study with genome-wide significance (odds ratio (OR) = 1.35; P = 2.3 × 10(-9)). The second SNP, rs12785878, is located near DHCR7 (Chr11), a genetic determinant of vitamin D insufficiency, and showed a size effect in MS similar to that recently observed in Type 1 diabetes (T1D; OR = 1.10; P = 0.009). ANKRD55 is a gene of unknown function, and is flanked proximally by the IL6ST-IL31RA gene cluster. However, rs6859219 did not show correlation with a series of haplotype-tagging SNPs covering IL6ST-IL31RA, analyzed in a subset of our dataset (D'< 0.31; r(2)< 0.011). Our results expand the number of risk genes shared between MS, RA and T1D.


  • D Otaegui
  • A Lopez de Lapuente
  • A Antigüedad
  • J Varadé
  • C Núñez
  • R Arroyo
  • E Urcelay
  • O Fernandez
  • L Leyva
  • M Fedetz
  • G Izquierdo
  • M Lucas
  • B Oliver-Martos
  • A Alcina
  • A Saiz
  • Y Blanco
  • M Comabella
  • X Montalban
  • J Olascoaga
  • F Matesanz
  • K Vandenbroeck
External organisations
  • University of the Basque Country
  • Biodonostia Health Research Institute
  • Basurto University Hospital
  • Hospital Clinico San Carlos de Madrid
  • University Hospital Virgen Macarena
  • Hospital Universitario Donostia
  • Vall d'Hebron University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Public Health, Global Health, Social Medicine and Epidemiology


  • Adult, Alleles, Ankyrin Repeat/genetics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Multiple Sclerosis/genetics, Oxidoreductases Acting on CH-CH Group Donors/genetics, Polymorphism, Single Nucleotide, Young Adult
Original languageEnglish
Pages (from-to)253-7
Number of pages5
JournalGenes and Immunity
Issue number3
Publication statusPublished - 2012 Apr
Publication categoryResearch
Externally publishedYes

Bibliographic note

I Alloza, D Otaegui, F Matesanz and K Vandenbroeck: These authors contributed equally to this work.