2013
Network-Based Multiple Sclerosis Pathway Analysis with GWAS Data from 15,000 Cases and 30,000 Controls
Consortium I, Baranzini S, Khankhanian P, Patsopoulos N, Li M, Stankovich J, Cotsapas C, Søndergaard H, Ban M, Barizzone N, Bergamaschi L, Booth D, Buck D, Cavalla P, Celius E, Comabella M, Comi G, Compston A, Cournu-Rebeix I, D’alfonso S, Damotte V, Din L, Dubois B, Elovaara I, Esposito F, Fontaine B, Franke A, Goris A, Gourraud P, Graetz C, Guerini F, Guillot-Noel L, Hafler D, Hakonarson H, Hall P, Hamsten A, Harbo H, Hemmer B, Hillert J, Kemppinen A, Kockum I, Koivisto K, Larsson M, Lathrop M, Leone M, Lill C, Macciardi F, Martin R, Martinelli V, Martinelli-Boneschi F, McCauley J, Myhr K, Naldi P, Olsson T, Oturai A, Pericak-Vance M, Perla F, Reunanen M, Saarela J, Saker-Delye S, Salvetti M, Sellebjerg F, Sørensen P, Spurkland A, Stewart G, Taylor B, Tienari P, Winkelmann J, Consortium W, Zipp F, Ivinson A, Haines J, Sawcer S, DeJager P, Hauser S, Oksenberg J. Network-Based Multiple Sclerosis Pathway Analysis with GWAS Data from 15,000 Cases and 30,000 Controls. American Journal Of Human Genetics 2013, 92: 854-865. PMID: 23731539, PMCID: PMC3958952, DOI: 10.1016/j.ajhg.2013.04.019.Peer-Reviewed Original ResearchConceptsPathway analysisNetwork-based pathway analysisGenome-wide association studiesSubnetworks of genesExtended linkage disequilibriumNon-HLA susceptibility lociHigh-confidence candidatesSubsequent genetic studiesComplex traitsSubstantial genetic componentSignificant lociGWAS dataAssociation studiesGene levelGenetic studiesNominal statistical evidenceSusceptibility lociGenesLinkage disequilibriumSusceptibility variantsGenetic componentRelated pathwaysLociHuman leukocyte antigen (HLA) regionPowerful approach
2010
Genome-wide Association Study in a High-Risk Isolate for Multiple Sclerosis Reveals Associated Variants in STAT3 Gene
Jakkula E, Leppä V, Sulonen AM, Varilo T, Kallio S, Kemppinen A, Purcell S, Koivisto K, Tienari P, Sumelahti ML, Elovaara I, Pirttilä T, Reunanen M, Aromaa A, Oturai AB, Søndergaard HB, Harbo HF, Mero IL, Gabriel SB, Mirel DB, Hauser SL, Kappos L, Polman C, De Jager PL, Hafler DA, Daly MJ, Palotie A, Saarela J, Peltonen L. Genome-wide Association Study in a High-Risk Isolate for Multiple Sclerosis Reveals Associated Variants in STAT3 Gene. American Journal Of Human Genetics 2010, 86: 285-291. PMID: 20159113, PMCID: PMC2820168, DOI: 10.1016/j.ajhg.2010.01.017.Peer-Reviewed Original ResearchConceptsSTAT3 geneGenome-wide association studiesRare risk allelesComplex traitsRisk lociRisk allelesAssociated variantsAssociation studiesRecent GWASInternal isolateLociCommon variantsGenetic riskGenesAllelesCritical roleSTAT3Small odds ratiosHeterogeneous populationVariantsGWASIsolatesProtective haplotypeTraitsSNPsGenetic variation in the IL7RA/IL7 pathway increases multiple sclerosis susceptibility
Zuvich RL, McCauley JL, Oksenberg JR, Sawcer SJ, De Jager PL, International Multiple Sclerosis Genetics Consortium, Aubin C, Cross AH, Piccio L, Aggarwal NT, Evans D, Hafler DA, Compston A, Hauser SL, Pericak-Vance MA, Haines JL. Genetic variation in the IL7RA/IL7 pathway increases multiple sclerosis susceptibility. Human Genetics 2010, 127: 525-535. PMID: 20112030, PMCID: PMC2854871, DOI: 10.1007/s00439-010-0789-4.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsGene regionCase-control data setsPutative functional relationshipsNovel gene regionsIndependent case-control data setDense SNP mapReceptor alpha-chain geneIllumina Infinium BeadChipExperiment-wise significanceNovel associationsAlpha chain geneGenetic architectureComplex traitsStrong genetic componentGenetic variationSNP mapInfinium BeadChipAffordable genotypingBiological pathwaysGenesGenetic componentChain geneTYK2 geneNumerous family studies