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PLoS One. 2016 Oct 20;11(10):e0163877. doi: 10.1371/journal.pone.0163877. eCollection 2016.

Genome-Wide Meta-Analysis of Sciatica in Finnish Population.

Author information

1
Health and Work Ability, Finnish Institute of Occupational Health, 00250 Helsinki, Finland.
2
Institute for Molecular Medicine Finland (FIMM), 00014 University of Helsinki, Helsinki, Finland.
3
Department of Public Health, 00014 University of Helsinki, Helsinki, Finland.
4
Population Health Unit, National Institute for Health and Welfare, 00251 Helsinki, Finland.
5
Faculty of Medicine, Institute of Health Sciences, University of Oulu, 90220 Oulu, Finland.
6
NMR Metabolomics Laboratory, University of Eastern Finland, Kuopio, Finland.
7
National Institute for Health and Welfare, Helsinki, Finland.
8
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, United States of America.
9
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States of America.
10
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, United Kingdom.
11
Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, 00271 Helsinki, Finland.
12
The Estonian Genome Center, University of Tartu, 51010 Tartu, Estonia.
13
Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere School of Medicine, 33520 Tampere, Finland.
14
Division of Medicine, Turku University Hospital, 20521 Turku, Finland.
15
Department of Medicine, University of Turku, 20521 Turku, Finland.
16
Department of Clinical Physiology, Tampere University Hospital, 33521 Tampere, Finland.
17
Department of Health, National Institute for Health and Welfare, 00251 Helsinki, Finland.
18
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20520 Turku, Finland.
19
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, 20521 Turku, Finland.
20
Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, United States of America.
21
Disability Prevention Centre, Finnish Institute of Occupational Health, 00250 Helsinki, Finland.

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.

PMID:
27764105
PMCID:
PMC5072673
DOI:
10.1371/journal.pone.0163877
[Indexed for MEDLINE]
Free PMC Article

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