دورية أكاديمية
Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations
| العنوان: | Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations |
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| المؤلفون: | Olafsson, S., Stridh, P., Bos, Steffan Daniel, Ingason, Andrés, Euesden, J, Sulem, Patrick, Thorleifsson, Gudmar, Gustafsson, O, Geirsson, AJ, Jóhannesson, Ari J., Thorsson, AV, Ludviksson, BR, Sigurgeirsson, Bardur, Jonasson, JG, Olafsson, E, Kristjansdottir, H, Olafsson, JH, Orvar, KB, Benediktsson, Rafn, Bjarnason, Ragnar, Kristjansdottir, Sjofn, Gislason, Thorarin, Valdimarsson, T, Mikaelsdottir, E, Sigurdsson, S, Jonsson, S, Rafnar, Thorunn, Aarsland, Dag, Djurovic, Srdjan, Fladby, Tormod, Knudsen, Gun Peggy S., Celius, Elisabeth Gulowsen, Myhr, Kjell-Morten, Gröndal, Gerdur, Steinsson, K, Valdimarsson, Helgi, Bjornsson, Sigurdur, Bjornsdottir, US, Bjornsson, Einar S., Nilsson, B, Andreassen, Ole Andreas, Alfredsson, Lars, Hillert, Jan, Kockum, Ingrid, Másson, Gísli, Thorsteinssdottir, U, Gudbjartsson, Daniel F., Stefansson, H, Hjaltason, H, Harbo, Hanne Flinstad, Olsson, T, Jonsdottir, I, Stefansson, K |
| المصدر: | NPJ Genomic Medicine |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2018 |
| المجموعة: | University of Bergen: Bergen Open Research Archive (BORA-UiB) |
| الوصف: | A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain. ; publishedVersion |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2056-7944 |
| العلاقة: | http://www.nature.com/articles/s41525-017-0027-2Test; Stiftelsen Kristian Gerhard Jebsen: SKGJ-MED-008; Norges forskningsråd: 223273; urn:issn:2056-7944; https://hdl.handle.net/1956/17600Test; https://doi.org/10.1038/s41525-017-0027-2Test; cristin:1549309 |
| DOI: | 10.1038/s41525-017-0027-2 |
| الإتاحة: | https://doi.org/10.1038/s41525-017-0027-2Test https://hdl.handle.net/1956/17600Test |
| حقوق: | Attribution CC BY ; http://creativecommons.org/licenses/by/4.0Test ; Copyright 2017 The Author(s) |
| رقم الانضمام: | edsbas.616F3443 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20567944 |
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| DOI: | 10.1038/s41525-017-0027-2 |