Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis

Eleni Zengini; Konstantinos Hatzikotoulas; Ioanna Tachmazidou; Julia Steinberg; Fernando P. Hartwig; Lorraine Southam; Sophie Hackinger; Cindy G. Boer; Unnur Styrkarsdottir; Arthur Gilly; Daniel Suveges; Britt Killian; Thorvaldur Ingvarsson; Helgi Jonsson; George C. Babis; Andrew McCaskie; Andre G. Uitterlinden; Joyce B.J. Van Meurs; Unnur Thorsteinsdottir; Kari Stefansson; George Davey Smith; Jeremy M. Wilkinson; Eleftheria Zeggini

doi:10.1038/s41588-018-0079-y

Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis

Eleni Zengini, Konstantinos Hatzikotoulas, Ioanna Tachmazidou, Julia Steinberg, Fernando P. Hartwig, Lorraine Southam, Sophie Hackinger, Cindy G. Boer, Unnur Styrkarsdottir, Arthur Gilly, Daniel Suveges, Britt Killian, Thorvaldur Ingvarsson, Helgi Jonsson, George C. Babis, Andrew McCaskie, Andre G. Uitterlinden, Joyce B.J. Van Meurs, Unnur Thorsteinsdottir, Kari StefanssonGeorge Davey Smith, Jeremy M. Wilkinson, Eleftheria Zeggini

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Abstract

Osteoarthritis is a common complex disease imposing a large public-health burden. Here, we performed a genome-wide association study for osteoarthritis, using data across 16.5 million variants from the UK Biobank resource. After performing replication and meta-analysis in up to 30,727 cases and 297,191 controls, we identified nine new osteoarthritis loci, in all of which the most likely causal variant was noncoding. For three loci, we detected association with biologically relevant radiographic endophenotypes, and in five signals we identified genes that were differentially expressed in degraded compared with intact articular cartilage from patients with osteoarthritis. We established causal effects on osteoarthritis for higher body mass index but not for triglyceride levels or genetic predisposition to type 2 diabetes.

Original language	English
Pages (from-to)	549-558
Number of pages	10
Journal	Nature Genetics
Volume	50
Issue number	4
DOIs	https://doi.org/10.1038/s41588-018-0079-y
State	Published - 1 Apr 2018
Externally published	Yes

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Zengini, E., Hatzikotoulas, K., Tachmazidou, I., Steinberg, J., Hartwig, F. P., Southam, L., Hackinger, S., Boer, C. G., Styrkarsdottir, U., Gilly, A., Suveges, D., Killian, B., Ingvarsson, T., Jonsson, H., Babis, G. C., McCaskie, A., Uitterlinden, A. G., Van Meurs, J. B. J., Thorsteinsdottir, U., ... Zeggini, E. (2018). Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis. Nature Genetics, 50(4), 549-558. https://doi.org/10.1038/s41588-018-0079-y

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title = "Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis",

abstract = "Osteoarthritis is a common complex disease imposing a large public-health burden. Here, we performed a genome-wide association study for osteoarthritis, using data across 16.5 million variants from the UK Biobank resource. After performing replication and meta-analysis in up to 30,727 cases and 297,191 controls, we identified nine new osteoarthritis loci, in all of which the most likely causal variant was noncoding. For three loci, we detected association with biologically relevant radiographic endophenotypes, and in five signals we identified genes that were differentially expressed in degraded compared with intact articular cartilage from patients with osteoarthritis. We established causal effects on osteoarthritis for higher body mass index but not for triglyceride levels or genetic predisposition to type 2 diabetes.",

author = "Eleni Zengini and Konstantinos Hatzikotoulas and Ioanna Tachmazidou and Julia Steinberg and Hartwig, {Fernando P.} and Lorraine Southam and Sophie Hackinger and Boer, {Cindy G.} and Unnur Styrkarsdottir and Arthur Gilly and Daniel Suveges and Britt Killian and Thorvaldur Ingvarsson and Helgi Jonsson and Babis, {George C.} and Andrew McCaskie and Uitterlinden, {Andre G.} and {Van Meurs}, {Joyce B.J.} and Unnur Thorsteinsdottir and Kari Stefansson and {Davey Smith}, George and Wilkinson, {Jeremy M.} and Eleftheria Zeggini",

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Zengini, E, Hatzikotoulas, K, Tachmazidou, I, Steinberg, J, Hartwig, FP, Southam, L, Hackinger, S, Boer, CG, Styrkarsdottir, U, Gilly, A, Suveges, D, Killian, B, Ingvarsson, T, Jonsson, H, Babis, GC, McCaskie, A, Uitterlinden, AG, Van Meurs, JBJ, Thorsteinsdottir, U, Stefansson, K, Davey Smith, G, Wilkinson, JM & Zeggini, E 2018, 'Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis', Nature Genetics, vol. 50, no. 4, pp. 549-558. https://doi.org/10.1038/s41588-018-0079-y

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AU - Zengini, Eleni

AU - Hatzikotoulas, Konstantinos

AU - Tachmazidou, Ioanna

AU - Steinberg, Julia

AU - Hartwig, Fernando P.

AU - Southam, Lorraine

AU - Hackinger, Sophie

AU - Boer, Cindy G.

AU - Styrkarsdottir, Unnur

AU - Gilly, Arthur

AU - Suveges, Daniel

AU - Killian, Britt

AU - Ingvarsson, Thorvaldur

AU - Jonsson, Helgi

AU - Babis, George C.

AU - McCaskie, Andrew

AU - Uitterlinden, Andre G.

AU - Van Meurs, Joyce B.J.

AU - Thorsteinsdottir, Unnur

AU - Stefansson, Kari

AU - Davey Smith, George

AU - Wilkinson, Jeremy M.

AU - Zeggini, Eleftheria

PY - 2018/4/1

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AB - Osteoarthritis is a common complex disease imposing a large public-health burden. Here, we performed a genome-wide association study for osteoarthritis, using data across 16.5 million variants from the UK Biobank resource. After performing replication and meta-analysis in up to 30,727 cases and 297,191 controls, we identified nine new osteoarthritis loci, in all of which the most likely causal variant was noncoding. For three loci, we detected association with biologically relevant radiographic endophenotypes, and in five signals we identified genes that were differentially expressed in degraded compared with intact articular cartilage from patients with osteoarthritis. We established causal effects on osteoarthritis for higher body mass index but not for triglyceride levels or genetic predisposition to type 2 diabetes.

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ER -

Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis

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