6533b854fe1ef96bd12aeab9
RESEARCH PRODUCT
IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci
Christian GiegerFederica EspositoB. BrynedaPer Soelberg SørensenLaura BergamaschiElisabeth Gulowsen CeliusIngrid KockumAn GorisAlastair CompstonSandra D'alfonsoRodney J. ScottP. I. W. De BakkerClive HawkinsBarbara Elaine StrangerÅSlaug R. LorentzenPaola CavallaAnnette Bang OturaiAnne SpurklandJanna SaarelaJanna SaarelaHelle Bach SøndergaardJeannette Lechner-scottJacob L. MccauleyAdrian J. IvinsonFilippo Martinelli-boneschiLars AlfredssonTomas OlssonCarmen Infante-duarteJonathan L. HainesSabine CepokAarno PalotieAarno PalotieLisa F. BarcellosStephen L. HauserRobert HeardManuel ComabellaFrauke ZippLeena PeltonenLeena PeltonenLeena PeltonenBénédicte DuboisRita DobosiMauri ReunanenJohn D. RiouxJorge R. OksenbergJuliane WinkelmannVirpi LeppaVirpi M. LeppäMaurizio LeoneKeijo KoivistoP. L. De JagerMargaret A. Pericak-vanceJan HillertRoberto BergamaschiCristin AubinDavid A. HaflerInger-lise MeroBruce A.c. CreeNeil RobertsonStephen SawcerFinn SellebjergWilliam S. BushIsabelle Cournu-rebeixIsabelle Cournu-rebeixIsabelle Cournu-rebeixHanne F. HarboB. HemmerLuisa BernardinelliLuisa BernardinelliGary W. BeechamMathew B CoxDavid R. BoothGraeme J. StewartNikolaos A. PatsopoulosMark J. DalyG. ComiBertrand FontaineBertrand FontaineBertrand Fontainesubject
Multiple SclerosisImmunologyGenome-wide association studyLocus (genetics)Single-nucleotide polymorphismBiologyPolymorphism Single NucleotideArticleInterleukin-12 Subunit p35Cell Line03 medical and health sciences0302 clinical medicineIL12AGeneticsmedicineHumansGenetic Predisposition to DiseaseAlleleGenetics (clinical)Cell Proliferation030304 developmental biologyGenetics0303 health sciencesTumor Suppressor ProteinsMultiple sclerosisCell cyclemedicine.disease3. Good healthCeliac DiseaseCase-Control StudiesImmunologyExpression quantitative trait lociLeukocytes MononuclearRGS Proteins030217 neurology & neurosurgerydescription
A recent meta-analysis identified seven single-nucleotide polymorphisms (SNPs) with suggestive evidence of association with multiple sclerosis (MS). We report an analysis of these polymorphisms in a replication study that includes 8,085 cases and 7,777 controls. A meta-analysis across the replication collections and a joint analysis with the discovery data set were performed. The possible functional consequences of the validated susceptibility loci were explored using RNA expression data. For all of the tested SNPs, the effect observed in the replication phase involved the same allele and the same direction of effect observed in the discovery phase. Three loci exceeded genome-wide significance in the joint analysis: RGS1 (P value = 3.55 × 10–9), IL12A (P = 3.08 × 10–8) and MPHOSPH9/CDK2AP1 (P = 3.96 × 10–8). The RGS1 risk allele is shared with celiac disease (CD), and the IL12A risk allele seems to be protective for celiac disease. Within the MPHOSPH9/CDK2AP1 locus, the risk allele correlates with diminished RNA expression of the cell cycle regulator CDK2AP1; this effect is seen in both lymphoblastic cell lines (P = 1.18 × 10–5) and in peripheral blood mononuclear cells from subjects with MS (P = 0.01). Thus, we report three new MS susceptibility loci, including a novel inflammatory disease locus that could affect autoreactive cell proliferation.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-06-17 | Genes & Immunity |