Lemmelä, SusannaSolovieva, SvetlanaShiri, RahmanBenner, ChristianHeliövaara, MarkkuKettunen, JohannesAnttila, VerneriRipatti, SamuliPerola, MarkusSeppälä, IlkkaJuonala, MarkusKähönen, MikaSalomaa, VeikkoViikari, JormaRaitakari, Olli T.Lehtimäki, TerhoPalotie, AarnoViikari-Juntura, EiraHusgafvel-Pursiainen, Kirsti2016-11-182016Lemmelä, S., S. Solovieva, R. Shiri, C. Benner, M. Heliövaara, J. Kettunen, V. Anttila, et al. 2016. “Genome-Wide Meta-Analysis of Sciatica in Finnish Population.” PLoS ONE 11 (10): e0163877. doi:10.1371/journal.pone.0163877. http://dx.doi.org/10.1371/journal.pone.0163877.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:29408145Sciatica 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.en-USBiology and Life SciencesComputational BiologyGenome AnalysisGenome-Wide Association StudiesGeneticsGenomicsHuman GeneticsMathematical and Statistical TechniquesStatistical MethodsMeta-AnalysisPhysical SciencesMathematicsStatistics (Mathematics)People and PlacesPopulation GroupingsEthnicitiesFinnsGenetic LociHeredityGenetic MappingVariant GenotypesMolecular BiologyMolecular Biology TechniquesGenotypingGene ExpressionGene RegulationHuman GenomicsJournal Article2016-11-1810.1371/journal.pone.0163877