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Genome-Wide Meta-Analysis of Sciatica in Finnish Population

Authors: Lemmelä, Susanna; Solovieva, Svetlana; Rahman, Shiri; Benner, Christian; Heliövaara, Markku; Kettunen, Johannes; Anttila, Vemeri; +12 Authors

Genome-Wide Meta-Analysis of Sciatica in Finnish Population

Abstract

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.

Countries
Finland, United States
Keywords

Heredity, Databases, Factual, Gene Expression, DISEASE, Public health care science, environmental and occupational health, Sciatica, Mathematical and Statistical Techniques, Gene Frequency, Ethnicities, TRANSCRIPTION, Finland, Q, R, Genomics, ASSOCIATION, ta3142, Genetic Mapping, Physical Sciences, CLASS II/III REGION, Medicine, Chromosomes, Human, Pair 6, Disease Susceptibility, Chromosomes, Human, Pair 9, Statistics (Mathematics), LOW-BACK-PAIN, Research Article, Genotyping, LUMBAR DISC DEGENERATION, Genotype, Biolääketieteet - Biomedicine, Science, Variant Genotypes, KNEE OSTEOARTHRITIS, Polymorphism, Single Nucleotide, Human Genomics, White People, NUCLEAR FACTOR-I, 616, Genome-Wide Association Studies, Genetics, Humans, Gene Regulation, Statistical Methods, Molecular Biology Techniques, Molecular Biology, Chromosomes, Human, Pair 15, ta1184, Biology and Life Sciences, Computational Biology, Human Genetics, MYOSIN-V FUNCTION, ta3121, Genome Analysis, GENE, Biomedicine, NFI Transcription Factors, Genetic Loci, Case-Control Studies, People and Places, Population Groupings, Mathematics, Finns, Meta-Analysis, Genome-Wide Association Study

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
28
Top 10%
Average
Top 10%
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gold