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

Unnur Styrkarsdottir; Gudmar Thorleifsson; Hafdis T Helgadottir; Nils Bomer; Sarah Metrustry; S Bierma-Zeinstra; Annelieke M Strijbosch; Evangelos Evangelou; Deborah Hart; Marian Beekman; Aslaug Jonasdottir; Asgeir Sigurdsson; Finnur F Eiriksson; Margret Thorsteinsdottir; Michael L Frigge; Augustine Kong; Sigurjon A Gudjonsson; Olafur T Magnusson; Gisli Masson; Albert Hofman; Nigel K Arden; Thorvaldur Ingvarsson; Stefan Lohmander; Margreet Kloppenburg; Fernando Rivadeneira; Rob G H H Nelissen; Tim Spector; Andre Uitterlinden; P Eline Slagboom; Unnur Thorsteinsdottir; Ingileif Jonsdottir; Ana M Valdes; Ingrid Meulenbelt; Joyce van Meurs; Helgi Jonsson; Kari Stefansson; The TREAT-OA Consortium

doi:10.1038/ng.2957

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

Unnur Styrkarsdottir, Gudmar Thorleifsson, Hafdis T Helgadottir, Nils Bomer, Sarah Metrustry, S Bierma-Zeinstra, Annelieke M Strijbosch, Evangelos Evangelou, Deborah Hart, Marian Beekman, Aslaug Jonasdottir, Asgeir Sigurdsson, Finnur F Eiriksson, Margret Thorsteinsdottir, Michael L Frigge, Augustine Kong, Sigurjon A Gudjonsson, Olafur T Magnusson, Gisli Masson, Albert HofmanNigel K Arden, Thorvaldur Ingvarsson, Stefan Lohmander, Margreet Kloppenburg, Fernando Rivadeneira, Rob G H H Nelissen, Tim Spector, Andre Uitterlinden, P Eline Slagboom, Unnur Thorsteinsdottir, Ingileif Jonsdottir, Ana M Valdes, Ingrid Meulenbelt, Joyce van Meurs, Helgi Jonsson, Kari Stefansson, The TREAT-OA Consortium

Twin Research & Genetic Epidemiology

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

121 Citations (Scopus)

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 × 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 × 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 × 10(-11) (rs3204689).

Original language	English
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 - May 2014

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Styrkarsdottir, U., Thorleifsson, G., Helgadottir, H. T., Bomer, N., Metrustry, S., Bierma-Zeinstra, S., Strijbosch, A. M., Evangelou, E., Hart, D., Beekman, M., Jonasdottir, A., Sigurdsson, A., Eiriksson, F. F., Thorsteinsdottir, M., Frigge, M. L., Kong, A., Gudjonsson, S. A., Magnusson, O. T., Masson, G., ... The TREAT-OA Consortium (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 × 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 × 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 × 10(-11) (rs3204689).",

author = "Unnur Styrkarsdottir and Gudmar Thorleifsson and Helgadottir, {Hafdis T} and Nils Bomer and Sarah Metrustry and S Bierma-Zeinstra and Strijbosch, {Annelieke M} and Evangelos Evangelou and Deborah Hart and Marian Beekman and Aslaug Jonasdottir and Asgeir Sigurdsson and Eiriksson, {Finnur F} and Margret Thorsteinsdottir and Frigge, {Michael L} and Augustine Kong and Gudjonsson, {Sigurjon A} and Magnusson, {Olafur T} and Gisli Masson and Albert Hofman and Arden, {Nigel K} and Thorvaldur Ingvarsson and Stefan Lohmander and Margreet Kloppenburg and Fernando Rivadeneira and Nelissen, {Rob G H H} and Tim Spector and Andre Uitterlinden and Slagboom, {P Eline} and Unnur Thorsteinsdottir and Ingileif Jonsdottir and Valdes, {Ana M} and Ingrid Meulenbelt and {van Meurs}, Joyce and Helgi Jonsson and Kari Stefansson and {The TREAT-OA Consortium}",

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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, A, 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 & The TREAT-OA Consortium 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, Unnur

AU - Thorleifsson, Gudmar

AU - Helgadottir, Hafdis T

AU - Bomer, Nils

AU - Metrustry, Sarah

AU - Bierma-Zeinstra, S

AU - Strijbosch, Annelieke M

AU - Evangelou, Evangelos

AU - Hart, Deborah

AU - Beekman, Marian

AU - Jonasdottir, Aslaug

AU - Sigurdsson, Asgeir

AU - Eiriksson, Finnur F

AU - Thorsteinsdottir, Margret

AU - Frigge, Michael L

AU - Kong, Augustine

AU - Gudjonsson, Sigurjon A

AU - Magnusson, Olafur T

AU - Masson, Gisli

AU - Hofman, Albert

AU - Arden, Nigel K

AU - Ingvarsson, Thorvaldur

AU - Lohmander, Stefan

AU - Kloppenburg, Margreet

AU - Rivadeneira, Fernando

AU - Nelissen, Rob G H H

AU - Spector, Tim

AU - Uitterlinden, Andre

AU - Slagboom, P Eline

AU - Thorsteinsdottir, Unnur

AU - Jonsdottir, Ingileif

AU - Valdes, Ana M

AU - Meulenbelt, Ingrid

AU - van Meurs, Joyce

AU - Jonsson, Helgi

AU - Stefansson, Kari

AU - The TREAT-OA Consortium

PY - 2014/5

Y1 - 2014/5

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 × 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 × 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 × 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 × 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 × 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 × 10(-11) (rs3204689).

U2 - 10.1038/ng.2957

DO - 10.1038/ng.2957

M3 - Article

C2 - 24728293

SN - 1061-4036

VL - 46

SP - 498

EP - 502

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

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

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