Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain

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Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain. / Suri, Pradeep; Palmer, Melody R.; Tsepilov, Yakov A. et al.

In: PLoS Genetics, Vol. 14, No. 9, e1007601, 01.09.2018, p. e1007601.

Research output: Contribution to journal › Article › peer-review

Harvard

Suri, P, Palmer, MR, Tsepilov, YA, Freidin, MB, Boer, CG, Yau, MS, Evans, DS, Gelemanovic, A, Bartz, TM, Nethander, M, Arbeeva, L, Karssen, L, Neogi, T, Campbell, A, Mellstrom, D, Ohlsson, C, Marshall, LM, Orwoll, E, Uitterlinden, A, Rotter, JI, Lauc, G, Psaty, BM, Karlsson, MK, Lane, NE, Jarvik, GP, Polasek, O, Hochberg, M, Jordan, JM, Van Meurs, JBJ, Jackson, R, Nielson, CM, Mitchell, BD, Smith, BH, Hayward, C, Smith, NL, Aulchenko, YS & Williams, FMK 2018, 'Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain', PLoS Genetics, vol. 14, no. 9, e1007601, pp. e1007601. https://doi.org/10.1371/journal.pgen.1007601

APA

Suri, P., Palmer, M. R., Tsepilov, Y. A., Freidin, M. B., Boer, C. G., Yau, M. S., Evans, D. S., Gelemanovic, A., Bartz, T. M., Nethander, M., Arbeeva, L., Karssen, L., Neogi, T., Campbell, A., Mellstrom, D., Ohlsson, C., Marshall, L. M., Orwoll, E., Uitterlinden, A., ... Williams, F. M. K. (2018). Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain. PLoS Genetics, 14(9), e1007601. [e1007601]. https://doi.org/10.1371/journal.pgen.1007601

Vancouver

Suri P, Palmer MR, Tsepilov YA, Freidin MB, Boer CG, Yau MS et al. Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain. PLoS Genetics. 2018 Sept 1;14(9):e1007601. e1007601. doi: 10.1371/journal.pgen.1007601

Author

Suri, Pradeep ; Palmer, Melody R. ; Tsepilov, Yakov A. et al. / Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain. In: PLoS Genetics. 2018 ; Vol. 14, No. 9. pp. e1007601.

BibTeX

@article{6cfea37d3efd4572a84078107b87df53,

title = "Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain",

abstract = "Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry were included from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and from the UK Biobank interim data release. 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<5×10−8. Suggestive (p<5×10−7) and genome-wide significant (p<5×10−8) variants were carried forward for replication or further investigation in the remaining UK Biobank participants not included in the discovery sample. The discovery sample comprised 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 = 7.2×10−10). This was subsequently replicated in 283,752 UK Biobank participants not included in the discovery sample, including 50,915 cases (OR 1.06, p = 5.3×10−11), and exceeded genome-wide significance in joint meta-analysis (OR 1.07, p = 4.5×10−19). 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 = 4.4×10−13), and an intronic variant, rs4384683, in DCC (OR 0.97, p = 2.4×10−10). 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).",

keywords = "Back Pain/genetics, Biomarkers, Tumor/genetics, Chronic Pain/genetics, DCC Receptor/genetics, DNA-Binding Proteins/genetics, European Continental Ancestry Group/genetics, Genetic Loci, Genome-Wide Association Study, Humans, Intracellular Signaling Peptides and Proteins/genetics, Introns/genetics, Polymorphism, Single Nucleotide, SOXD Transcription Factors/genetics, COTWIN CONTROL, RISK-FACTORS, GENETIC-VARIANTS, HERITABILITY, NETRIN-1, BODY-MASS INDEX, INTERVERTEBRAL DISC, LD SCORE REGRESSION, TRAITS, KNEE OSTEOARTHRITIS",

author = "Pradeep Suri and Palmer, {Melody R.} and Tsepilov, {Yakov A.} and Freidin, {Maxim B.} and Boer, {Cindy G.} and Yau, {Michelle S.} and Evans, {Daniel S.} and Andrea Gelemanovic and Bartz, {Traci M.} and Maria Nethander and Liubov Arbeeva and Lennart Karssen and Tuhina Neogi and Archie Campbell and Dan Mellstrom and Claes Ohlsson and Marshall, {Lynn M.} and Eric Orwoll and Andre Uitterlinden and Rotter, {Jerome I.} and Gordan Lauc and Psaty, {Bruce M.} and Karlsson, {Magnus K.} and Lane, {Nancy E.} and Jarvik, {Gail P.} and Ozren Polasek and Marc Hochberg and Jordan, {Joanne M.} and {Van Meurs}, {Joyce B.J.} and Rebecca Jackson and Nielson, {Carrie M.} and Mitchell, {Braxton D.} and Smith, {Blair H.} and Caroline Hayward and Smith, {Nicholas L.} and Aulchenko, {Yurii S.} and Williams, {Frances M.K.}",

year = "2018",

month = sep,

day = "1",

doi = "10.1371/journal.pgen.1007601",

language = "English",

volume = "14",

pages = "e1007601",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "9",

}

RIS

TY - JOUR

T1 - Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain

AU - Suri, Pradeep

AU - Palmer, Melody R.

AU - Tsepilov, Yakov A.

AU - Freidin, Maxim B.

AU - Boer, Cindy G.

AU - Yau, Michelle S.

AU - Evans, Daniel S.

AU - Gelemanovic, Andrea

AU - Bartz, Traci M.

AU - Nethander, Maria

AU - Arbeeva, Liubov

AU - Karssen, Lennart

AU - Neogi, Tuhina

AU - Campbell, Archie

AU - Mellstrom, Dan

AU - Ohlsson, Claes

AU - Marshall, Lynn M.

AU - Orwoll, Eric

AU - Uitterlinden, Andre

AU - Rotter, Jerome I.

AU - Lauc, Gordan

AU - Psaty, Bruce M.

AU - Karlsson, Magnus K.

AU - Lane, Nancy E.

AU - Jarvik, Gail P.

AU - Polasek, Ozren

AU - Hochberg, Marc

AU - Jordan, Joanne M.

AU - Van Meurs, Joyce B.J.

AU - Jackson, Rebecca

AU - Nielson, Carrie M.

AU - Mitchell, Braxton D.

AU - Smith, Blair H.

AU - Hayward, Caroline

AU - Smith, Nicholas L.

AU - Aulchenko, Yurii S.

AU - Williams, Frances M.K.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry were included from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and from the UK Biobank interim data release. 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<5×10−8. Suggestive (p<5×10−7) and genome-wide significant (p<5×10−8) variants were carried forward for replication or further investigation in the remaining UK Biobank participants not included in the discovery sample. The discovery sample comprised 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 = 7.2×10−10). This was subsequently replicated in 283,752 UK Biobank participants not included in the discovery sample, including 50,915 cases (OR 1.06, p = 5.3×10−11), and exceeded genome-wide significance in joint meta-analysis (OR 1.07, p = 4.5×10−19). 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 = 4.4×10−13), and an intronic variant, rs4384683, in DCC (OR 0.97, p = 2.4×10−10). 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).

AB - Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry were included from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and from the UK Biobank interim data release. 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<5×10−8. Suggestive (p<5×10−7) and genome-wide significant (p<5×10−8) variants were carried forward for replication or further investigation in the remaining UK Biobank participants not included in the discovery sample. The discovery sample comprised 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 = 7.2×10−10). This was subsequently replicated in 283,752 UK Biobank participants not included in the discovery sample, including 50,915 cases (OR 1.06, p = 5.3×10−11), and exceeded genome-wide significance in joint meta-analysis (OR 1.07, p = 4.5×10−19). 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 = 4.4×10−13), and an intronic variant, rs4384683, in DCC (OR 0.97, p = 2.4×10−10). 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).

KW - Back Pain/genetics

KW - Biomarkers, Tumor/genetics

KW - Chronic Pain/genetics

KW - DCC Receptor/genetics

KW - DNA-Binding Proteins/genetics

KW - European Continental Ancestry Group/genetics

KW - Genetic Loci

KW - Genome-Wide Association Study

KW - Humans

KW - Intracellular Signaling Peptides and Proteins/genetics

KW - Introns/genetics

KW - Polymorphism, Single Nucleotide

KW - SOXD Transcription Factors/genetics

KW - COTWIN CONTROL

KW - RISK-FACTORS

KW - GENETIC-VARIANTS

KW - HERITABILITY

KW - NETRIN-1

KW - BODY-MASS INDEX

KW - INTERVERTEBRAL DISC

KW - LD SCORE REGRESSION

KW - TRAITS

KW - KNEE OSTEOARTHRITIS

UR - http://www.scopus.com/inward/record.url?scp=85054564552&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1007601

DO - 10.1371/journal.pgen.1007601

M3 - Article

C2 - 30261039

AN - SCOPUS:85054564552

VL - 14

SP - e1007601

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 9

M1 - e1007601

ER -

ID: 17034752