A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Genome-Wide Meta-Analysis of Sciatica in Finnish Population
Tekijät: Lemmela S, Solovieva S, Shiri R, Benner C, Heliovaara M, Kettunen J, Anttila V, Ripatti S, Perola M, Seppala I, Juonala M, Kahonen M, Salomaa V, Viikari J, Raitakari OT, Lehtimaki T, Palotie A, Viikari-Juntura E, Husgafvel-Pursiainen K
Kustantaja: PUBLIC LIBRARY SCIENCE
Julkaisuvuosi: 2016
Journal: PLoS ONE
Tietokannassa oleva lehden nimi: PLOS ONE
Lehden akronyymi: PLOS ONE
Artikkelin numero: ARTN e0163877
Vuosikerta: 11
Numero: 10
Sivujen määrä: 18
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0163877
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 chr9:14344410:1 (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 (chr9:14344410:1, 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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
