Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31

U Styrkarsdottir; G Thorleifsson; HT Helgadottir; N Bomer; S Metrustry; Sita Bierma - Zeinstra; AM Strijbosch; E Evangelou; Daphne Hart; M Beekman; A Jonasdottir; A Sigurdsson; FF Eiriksson; M Thorsteinsdottir; ML Frigge; A Kong; SA Gudjonsson; OT Magnusson; G Masson; Bert Hofman; NK Arden; T Ingvarsson; S Lohmander; M Kloppenburg; Fernando Rivadeneira; RGHH Nelissen; T Spector; André Uitterlinden; PE (Eline) Slagboom; U Thorsteinsdottir; I Jonsdottir; AM Valdes; I Meulenbelt; Joyce van Meurs; H Jonsson; K Stefansson

doi:10.1038/ng.2957

Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31

U Styrkarsdottir, G Thorleifsson, HT Helgadottir, N Bomer, S Metrustry, Sita Bierma - Zeinstra, AM Strijbosch, E Evangelou, Daphne Hart, M Beekman, A Jonasdottir, A Sigurdsson, FF Eiriksson, M Thorsteinsdottir, ML Frigge, A Kong, SA Gudjonsson, OT Magnusson, G Masson, Bert HofmanNK Arden, T Ingvarsson, S Lohmander, M Kloppenburg, Fernando Rivadeneira, RGHH Nelissen, T Spector, André Uitterlinden, PE (Eline) Slagboom, U Thorsteinsdottir, I Jonsdottir, AM Valdes, I Meulenbelt, Joyce van Meurs, H Jonsson, K Stefansson

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

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Abstract

Osteoarthritis is the most common form of arthritis and is a major cause of pain and disability in the elderly. To search for sequence variants that confer risk of osteoarthritis of the hand, we carried out a genome-wide association study (GWAS) in subjects with severe hand osteoarthritis, using variants identified through the whole-genome sequencing of 2,230 Icelanders. We found two significantly associated loci in the Icelandic discovery set: at 15q22 (frequency of 50.7%, odds ratio (OR) = 1.51, P = 3.99 x 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 x 10(-10)). Among the carriers of the variant at 1p31 is a family with several members in whom the risk allele segregates with osteoarthritis. The variants within the ALDH1A2 gene were confirmed in replication sets from The Netherlands and the UK, yielding an overall association of OR = 1.46 and P= 1.1 x 10(-11) (rs3204689).

Original language	Undefined/Unknown
Pages (from-to)	498-502
Number of pages	5
Journal	Nature Genetics
Volume	46
Issue number	5
DOIs	https://doi.org/10.1038/ng.2957
Publication status	Published - 2014

Research programs

EMC MM-01-39-09-A
EMC MM-01-51-01
EMC NIHES-01-64-01
EMC NIHES-02-67-01

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10.1038/ng.2957

http://hdl.handle.net/1765/58616

Cite this

Styrkarsdottir, U., Thorleifsson, G., Helgadottir, HT., Bomer, N., Metrustry, S., Bierma - Zeinstra, S., Strijbosch, AM., Evangelou, E., Hart, D., Beekman, M., Jonasdottir, A., Sigurdsson, A., Eiriksson, FF., Thorsteinsdottir, M., Frigge, ML., Kong, A., Gudjonsson, SA., Magnusson, OT., Masson, G., ... Stefansson, K. (2014). Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31. Nature Genetics, 46(5), 498-502. https://doi.org/10.1038/ng.2957

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title = "Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31",

abstract = "Osteoarthritis is the most common form of arthritis and is a major cause of pain and disability in the elderly. To search for sequence variants that confer risk of osteoarthritis of the hand, we carried out a genome-wide association study (GWAS) in subjects with severe hand osteoarthritis, using variants identified through the whole-genome sequencing of 2,230 Icelanders. We found two significantly associated loci in the Icelandic discovery set: at 15q22 (frequency of 50.7%, odds ratio (OR) = 1.51, P = 3.99 x 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 x 10(-10)). Among the carriers of the variant at 1p31 is a family with several members in whom the risk allele segregates with osteoarthritis. The variants within the ALDH1A2 gene were confirmed in replication sets from The Netherlands and the UK, yielding an overall association of OR = 1.46 and P= 1.1 x 10(-11) (rs3204689).",

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Styrkarsdottir, U, Thorleifsson, G, Helgadottir, HT, Bomer, N, Metrustry, S, Bierma - Zeinstra, S, Strijbosch, AM, Evangelou, E, Hart, D, Beekman, M, Jonasdottir, A, Sigurdsson, A, Eiriksson, FF, Thorsteinsdottir, M, Frigge, ML, Kong, A, Gudjonsson, SA, Magnusson, OT, Masson, G, Hofman, B, Arden, NK, Ingvarsson, T, Lohmander, S, Kloppenburg, M, Rivadeneira, F, Nelissen, RGHH, Spector, T, Uitterlinden, A, Slagboom, PE, Thorsteinsdottir, U, Jonsdottir, I, Valdes, AM, Meulenbelt, I, van Meurs, J, Jonsson, H & Stefansson, K 2014, 'Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31', Nature Genetics, vol. 46, no. 5, pp. 498-502. https://doi.org/10.1038/ng.2957

TY - JOUR

T1 - Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31

AU - Styrkarsdottir, U

AU - Thorleifsson, G

AU - Helgadottir, HT

AU - Bomer, N

AU - Metrustry, S

AU - Bierma - Zeinstra, Sita

AU - Strijbosch, AM

AU - Evangelou, E

AU - Hart, Daphne

AU - Beekman, M

AU - Jonasdottir, A

AU - Sigurdsson, A

AU - Eiriksson, FF

AU - Thorsteinsdottir, M

AU - Frigge, ML

AU - Kong, A

AU - Gudjonsson, SA

AU - Magnusson, OT

AU - Masson, G

AU - Hofman, Bert

AU - Arden, NK

AU - Ingvarsson, T

AU - Lohmander, S

AU - Kloppenburg, M

AU - Rivadeneira, Fernando

AU - Nelissen, RGHH

AU - Spector, T

AU - Uitterlinden, André

AU - Slagboom, PE (Eline)

AU - Thorsteinsdottir, U

AU - Jonsdottir, I

AU - Valdes, AM

AU - Meulenbelt, I

AU - van Meurs, Joyce

AU - Jonsson, H

AU - Stefansson, K

PY - 2014

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N2 - Osteoarthritis is the most common form of arthritis and is a major cause of pain and disability in the elderly. To search for sequence variants that confer risk of osteoarthritis of the hand, we carried out a genome-wide association study (GWAS) in subjects with severe hand osteoarthritis, using variants identified through the whole-genome sequencing of 2,230 Icelanders. We found two significantly associated loci in the Icelandic discovery set: at 15q22 (frequency of 50.7%, odds ratio (OR) = 1.51, P = 3.99 x 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 x 10(-10)). Among the carriers of the variant at 1p31 is a family with several members in whom the risk allele segregates with osteoarthritis. The variants within the ALDH1A2 gene were confirmed in replication sets from The Netherlands and the UK, yielding an overall association of OR = 1.46 and P= 1.1 x 10(-11) (rs3204689).

AB - Osteoarthritis is the most common form of arthritis and is a major cause of pain and disability in the elderly. To search for sequence variants that confer risk of osteoarthritis of the hand, we carried out a genome-wide association study (GWAS) in subjects with severe hand osteoarthritis, using variants identified through the whole-genome sequencing of 2,230 Icelanders. We found two significantly associated loci in the Icelandic discovery set: at 15q22 (frequency of 50.7%, odds ratio (OR) = 1.51, P = 3.99 x 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 x 10(-10)). Among the carriers of the variant at 1p31 is a family with several members in whom the risk allele segregates with osteoarthritis. The variants within the ALDH1A2 gene were confirmed in replication sets from The Netherlands and the UK, yielding an overall association of OR = 1.46 and P= 1.1 x 10(-11) (rs3204689).

U2 - 10.1038/ng.2957

DO - 10.1038/ng.2957

M3 - Article

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SN - 1061-4036

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SP - 498

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