Genome-wide association study in a high-risk isolate for multiple sclerosis reveals associated variants in STAT3 gene

Jakkula, Eveliina and Leppä, Virpi and Sulonen, Anna-Maija and Varilo, Teppo and Kallio, Suvi and Kemppinen, Anu and Purcell, Shaun and Koivisto, Keijo and Tienari, Pentti and Sumelahti, Marja-Liisa and Elovaara, Irina and Pirttilä, Tuula and Reunanen, Mauri and Aromaa, Arpo and Oturai, Annette Bang and Søndergaard, Helle Bach and Harbo, Hanne F. and Mero, Inger-Lise and Gabriel, Stacey B. and Mirel, Daniel B. and Hauser, Stephen L. and Kappos, Ludwig and Polman, Chris and De Jager, Philip L. and Hafler, David A. and Daly, Mark J. and Palotie, Aarno and Saarela, Janna and Peltonen, Leena. (2010) Genome-wide association study in a high-risk isolate for multiple sclerosis reveals associated variants in STAT3 gene. American journal of human genetics, Vol. 86, H. 2. pp. 285-291.

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Official URL: http://edoc.unibas.ch/dok/A6004528

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Genetic risk for multiple sclerosis (MS) is thought to involve both common and rare risk alleles. Recent GWAS and subsequent meta-analysis have established the critical role of the HLA locus and identified new common variants associated to MS. These variants have small odds ratios (ORs) and explain only a fraction of the genetic risk. To expose potentially rare, high-impact alleles, we conducted a GWAS of 68 distantly related cases and 136 controls from a high-risk internal isolate of Finland with increased prevalence and familial occurrence of MS. The top 27 loci with p > 10(-4) were tested in 711 cases and 1029 controls from Finland, and the top two findings were validated in 3859 cases and 9110 controls from more heterogeneous populations. SNP (rs744166) within the STAT3 gene was associated to MS (p = 2.75 x 10(-10), OR 0.87, confidence interval 0.83-0.91). The protective haplotype for MS in STAT3 is a risk allele for Crohn disease, implying that STAT3 represents a shared risk locus for at least two autoimmune diseases. This study also demonstrates the potential of special isolated populations in search for variants contributing to complex traits.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Neurologie > Neuroimmunologie (Kappos)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Neurologie > Neuroimmunologie (Kappos)
UniBasel Contributors:Kappos, Ludwig
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Univ. of Chicago Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:13
Deposited On:26 Apr 2013 06:55

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