Genome-wide Association Study in a High-Risk Isolate for Multiple Sclerosis Reveals Associated Variants in STAT3 Gene
| Autor: | Teppo Varilo, Chris H. Polman, Maria-Liisa Sumelahti, Stacey Gabriel, Anna-Maija Kristiina Sulonen, Arpo Aromaa, David A. Hafler, Pentti J. Tienari, Inger-Lise Mero, Eveliina Jakkula, Stephen L. Hauser, Aarno Palotie, Daniel B. Mirel, Mauri Reunanen, Leena Peltonen, Ludwig Kappos, Shaun Purcell, Annette Bang Oturai, Anu Kemppinen, Helle Bach Søndergaard, Irina Elovaara, Hanne F. Harbo, Philip L. De Jager, Tuula Pirttilä, Keijo Koivisto, Virpi Leppa, Janna Saarela, Mark J. Daly, Suvi P. Kallio |
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| Přispěvatelé: | Neurology, NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases |
| Rok vydání: | 2010 |
| Předmět: |
STAT3 Transcription Factor
Linkage disequilibrium Multiple Sclerosis Genome-wide association study Single-nucleotide polymorphism Locus (genetics) Biology Polymorphism Single Nucleotide Linkage Disequilibrium 03 medical and health sciences 0302 clinical medicine Report Genotype Genetics Humans Genetic Predisposition to Disease Genetics(clinical) Allele Base Pairing Alleles Genetics (clinical) 030304 developmental biology 0303 health sciences Haplotype Reproducibility of Results Odds ratio Genetics Population Haplotypes Case-Control Studies 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | American journal of human genetics, 86(2), 285-291. Cell Press Jakkula, E, Leppa, V, Sulonen, A M, Varilo, T, Kallio, S, Kemppinen, A, Purcell, S, Koivisto, K, Tienari, P, Sumelahti, M L, Elovaara, I, Pirttila, T, Reunanen, M, Aromaa, A, Oturai, A B, Sondergaard, H B, Harbo, H F, Mero, I L, Gabriel, S B, Mirel, D B, Hauser, S L, Kappos, L, Polman, C H, de Jager, P L, Hafler, D A, Daly, M J, Palotie, A, Saarela, J & Peltonen, L 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, no. 2, pp. 285-291 . https://doi.org/10.1016/j.ajhg.2010.01.017 |
| ISSN: | 0002-9297 |
| DOI: | 10.1016/j.ajhg.2010.01.017 |
| Popis: | 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 p10(-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. |
| Databáze: | OpenAIRE |
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