Abstract
A rare functional variant within the TYK2 gene (rs34536443) has been reported as protective in multiple sclerosis (MS) in recent studies. However, because of the low frequency of the minor allele (minor allele frequency=0.04), genome-wide significant association has been hard to establish. We genotyped 5429 Nordic MS cases and 6167 healthy controls for this TYK2 non-synonymous single-nucleotide polymorphism (ns-SNP), and combined the Nordic genotype data with raw genotypes from previous studies. The combined Nordic analysis showed significant association with MS (P=5 × 10−4, odds ratio (OR) 0.78), and by mega-analysis of 10 642 MS patients, 10 620 controls and 2110 MS trios, the association at genome-wide significance level (P=5.08 × 10−9, OR 0.77) was shown.
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Acknowledgements
We thank MS patients and healthy controls for their participation in the study. We gratefully acknowledge the contribution made by the various members of the International Multiple Sclerosis Genetics Consortium (IMSGC) (https://www.imsgc.org), in particular, Dr Stephen Sawcer, as well as the Wellcome Trust Case Control Consortium (WTCCC), who kindly supplied their data for inclusion in this analysis. The Oslo MS genetics group is supported by grants from The Research Council of Norway; Scientific Advisory Council Ullevål, Oslo University Hospital; South-Eastern Norway Regional Health Authority, Norwegian Foundation for Health and Rehabilitation and Odd Fellow MS society. Contributors to the collection of samples and clinical data in the Norwegian MS Registry and Biobank are acknowledged for their contributions. The Norwegian MS Registry and Biobank is supported by The Research Council of Norway, Haukeland University Hospital and Western Norway Regional Health Authority. The Institute of Medical Genetics, Ullevål, Oslo University Hospital, and the Norwegian Bone Marrow Donor Registry, Rikshospitalet, Oslo University Hospital are acknowledged for providing Norwegian controls. The Finnish MS group is supported by Neuropromise EU grant LSHM-CT-2005–018637, The Center of Excellence for Disease Genetics of the Academy of Finland, the Sigrid Juselius Foundation, Helsinki University Central Hospital Research Foundation, and the Helsinki Biomedical Graduate School (AK). The MGEN consortium neurologists Dr Keijo Koivisto, Dr Tuula Pirttilä, Dr Mauri Reunanen, and Dr Pentti Tienari are acknowledged for the Finnish MS patient samples and the clinical data. The Danish Multiple Sclerosis Society is acknowledged for financial support of the Danish MS research. The Swedish group was funded by the Bibbi and Nils Jensen Foundation, Montel Williams foundation and the Söderbergs foundation, the Swedish Research Council, Karolinska Institutet, and the 6th Framework Program of the European Union, NeuroproMiSe (LSHM-CT-2005–018637).
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Mero, IL., Lorentzen, Å., Ban, M. et al. A rare variant of the TYK2 gene is confirmed to be associated with multiple sclerosis. Eur J Hum Genet 18, 502–504 (2010). https://doi.org/10.1038/ejhg.2009.195
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DOI: https://doi.org/10.1038/ejhg.2009.195
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