Genome-Wide Meta-Analysis of Sciatica in Finnish Population
Public Library of Science, 2016
Online
academicJournal
Zugriff:
Sciatica or the sciatic syndrome is a common and often disabling low back disorder in the working-age population. It has a relatively high heritability but poorly understood molecular mechanisms. The Finnish population is a genetic isolate where small founder population and bottleneck events have led to enrichment of certain rare and low frequency variants. We performed here the first genome-wide association (GWAS) and meta-analysis of sciatica. The meta-analysis was conducted across two GWAS covering 291 Finnish sciatica cases and 3671 controls genotyped and imputed at 7.7 million autosomal variants. The most promising loci (p<1x10-6) were replicated in 776 Finnish sciatica patients and 18,489 controls. We identified five intragenic variants, with relatively low frequencies, at two novel loci associated with sciatica at genome-wide significance. These included chr9:14344410:I (rs71321981) at 9p22.3 (NFIB gene; p = 1.30x10-8, MAF = 0.08) and four variants at 15q21.2: rs145901849, rs80035109, rs190200374 and rs117458827 (MYO5A; p = 1.34x10-8, MAF = 0.06; p = 2.32x10-8, MAF = 0.07; p = 3.85x10-8, MAF = 0.06; p = 4.78x10-8, MAF = 0.07, respectively). The most significant association in the meta-analysis, a single base insertion rs71321981 within the regulatory region of the transcription factor NFIB, replicated in an independent Finnish population sample (p = 0.04). Despite identifying 15q21.2 as a promising locus, we were not able to replicate it. It was differentiated; the lead variants within 15q21.2 were more frequent in Finland (6–7%) than in other European populations (1–2%). Imputation accuracies of the three significantly associated variants (chr9:14344410:I, rs190200374, and rs80035109) were validated by genotyping. In summary, our results suggest a novel locus, 9p22.3 (NFIB), which may be involved in susceptibility to sciatica. In addition, another locus, 15q21.2, emerged as a promising one, but failed to replicate.
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Genome-Wide Meta-Analysis of Sciatica in Finnish Population
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Autor/in / Beteiligte Person: | Lemmelä, Susanna ; Solovieva, Svetlana ; Shiri, Rahman ; Benner, Christian ; Heliövaara, Markku ; Kettunen, Johannes ; Anttila, Verneri ; Ripatti, Samuli ; Perola, Markus ; Seppälä, Ilkka ; Juonala, Markus ; Kähönen, Mika ; Salomaa, Veikko ; Viikari, Jorma ; Raitakari, Olli T. ; Lehtimäki, Terho ; Palotie, Aarno ; Viikari-Juntura, Eira ; Husgafvel-Pursiainen, Kirsti |
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Veröffentlichung: | Public Library of Science, 2016 |
Medientyp: | academicJournal |
ISSN: | 1932-6203 (print) |
DOI: | 10.1371/journal.pone.0163877 |
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