Genome-wide Meta-analysis of 158,000 Individuals of European Ancestry Identifies Three Loci Associated with Chronic Back Pain
By
Pradeep Suri,
Melody R Palmer,
Yakov A. Tsepilov,
Maxim Freidin,
Cindy G Boer,
Michelle S Yau,
Daniel S Evans,
Andrea Gelemanovic,
Traci M Bartz,
Maria Nethander,
Liubov Arbeeva,
Lennart Karssen,
Tuhina Neogi,
Archie Campbell,
Dan Mellstrom,
Claes Ohlsson,
Lynn M Marshall,
Eric Orwoll,
Andre Uitterlinden,
Jerome Rotter,
Gordan Lauc,
Bruce M Psaty,
Magnus K Karlsson,
Nancy E Lane,
Gail Jarvik,
Ozren Polasek,
Marc Hochberg,
Joanne M Jordan,
Joyce B. J. Van Meurs,
Rebecca Jackson,
Carrie M Nielson,
Braxton D Mitchell,
Blair H Smith,
Caroline Hayward,
Jennifer A Smith,
Yurii S. Aulchenko,
Frances M. K. Williams
Posted 08 Jan 2018
bioRxiv DOI: 10.1101/244483
(published DOI: 10.1371/journal.pgen.1007601)
OBJECTIVES: To conduct a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). METHODS: Adults of European ancestry were included from 16 cohorts in Europe and North America. CBP cases were defined as those reporting back pain present for >3-6 months; non-cases were included as comparisons ('controls'). Each cohort conducted genotyping using commercially available arrays followed by imputation. GWAS used logistic regression models with additive genetic effects, adjusting for age, sex, study-specific covariates, and population substructure. The threshold for genome-wide significance in the fixed-effect inverse-variance weighted meta-analysis was p<5x10-8. Suggestive (p<5x10-7) and genome-wide significant (p<5x10-8) variants were carried forward for replication or further investigation in an independent sample. RESULTS: The discovery sample was comprised of 158,025 individuals, including 29,531 CBP cases. A genome-wide significant association was found for the intronic variant rs12310519 in SOX5 (OR 1.08, p=7.2x10-10). This was subsequently replicated in an independent sample of 283,752 subjects, including 50,915 cases (OR 1.06, p=5.3x10-11), and exceeded genome-wide significance in joint meta-analysis (OR=1.07, p=4.5x10-19). We found suggestive associations at three other loci in the discovery sample, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant, rs7833174, located between CCDC26 and GSDMC (OR 1.05, p=4.4x10-13), and an intronic variant, rs4384683, in DCC (OR 0.97, p=2.4x10-10). DISCUSSION: In this first reported meta-analysis of GWAS for CBP, we identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC).
Download data
- Downloaded 1,003 times
- Download rankings, all-time:
- Site-wide: 26,405
- In genomics: 2,401
- Year to date:
- Site-wide: 130,058
- Since beginning of last month:
- Site-wide: 121,536
Altmetric data
Downloads over time
Distribution of downloads per paper, site-wide
PanLingua
News
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!