Genome-Wide Meta-Analysis of Sciatica in Finnish Population.
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 le...
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0163877&type=printable |
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| author | Susanna Lemmelä Svetlana Solovieva Rahman Shiri Christian Benner Markku Heliövaara Johannes Kettunen Verneri Anttila Samuli Ripatti Markus Perola Ilkka Seppälä Markus Juonala Mika Kähönen Veikko Salomaa Jorma Viikari Olli T Raitakari Terho Lehtimäki Aarno Palotie Eira Viikari-Juntura Kirsti Husgafvel-Pursiainen |
| author_facet | Susanna Lemmelä Svetlana Solovieva Rahman Shiri Christian Benner Markku Heliövaara Johannes Kettunen Verneri Anttila Samuli Ripatti Markus Perola Ilkka Seppälä Markus Juonala Mika Kähönen Veikko Salomaa Jorma Viikari Olli T Raitakari Terho Lehtimäki Aarno Palotie Eira Viikari-Juntura Kirsti Husgafvel-Pursiainen |
| author_sort | Susanna Lemmelä |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-12f187892c2443bf8e8dc24dcd7d6f41 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-12f187892c2443bf8e8dc24dcd7d6f412025-08-20T03:24:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011110e016387710.1371/journal.pone.0163877Genome-Wide Meta-Analysis of Sciatica in Finnish Population.Susanna LemmeläSvetlana SolovievaRahman ShiriChristian BennerMarkku HeliövaaraJohannes KettunenVerneri AnttilaSamuli RipattiMarkus PerolaIlkka SeppäläMarkus JuonalaMika KähönenVeikko SalomaaJorma ViikariOlli T RaitakariTerho LehtimäkiAarno PalotieEira Viikari-JunturaKirsti Husgafvel-PursiainenSciatica 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0163877&type=printable |
| spellingShingle | Susanna Lemmelä Svetlana Solovieva Rahman Shiri Christian Benner Markku Heliövaara Johannes Kettunen Verneri Anttila Samuli Ripatti Markus Perola Ilkka Seppälä Markus Juonala Mika Kähönen Veikko Salomaa Jorma Viikari Olli T Raitakari Terho Lehtimäki Aarno Palotie Eira Viikari-Juntura Kirsti Husgafvel-Pursiainen Genome-Wide Meta-Analysis of Sciatica in Finnish Population. PLoS ONE |
| title | Genome-Wide Meta-Analysis of Sciatica in Finnish Population. |
| title_full | Genome-Wide Meta-Analysis of Sciatica in Finnish Population. |
| title_fullStr | Genome-Wide Meta-Analysis of Sciatica in Finnish Population. |
| title_full_unstemmed | Genome-Wide Meta-Analysis of Sciatica in Finnish Population. |
| title_short | Genome-Wide Meta-Analysis of Sciatica in Finnish Population. |
| title_sort | genome wide meta analysis of sciatica in finnish population |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0163877&type=printable |
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