Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers

Darren Plant; Edward Flynn; Hamdi Mbarek; Philippe Dieudé; François Cornelis; Lisbeth Arlestig; Solbritt Rantapää Dahlqvist; George Goulielmos; Dimitrios T Boumpas; Prodromos Sidiropoulos; Julia S Johansen; Lykke M Ørnbjerg; Merete Lund Hetland; Lars Klareskog; Andrew Filer; Christopher D Buckley; Karim Raza; Torsten Witte; Reinhold E Schmidt; Jane Worthington

doi:http://dx.doi.org/10.1136/ard.2009.121020

Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers

Darren Plant, Edward Flynn, Hamdi Mbarek, Philippe Dieudé, François Cornelis, Lisbeth Arlestig, Solbritt Rantapää Dahlqvist, George Goulielmos, Dimitrios T Boumpas, Prodromos Sidiropoulos, Julia S Johansen, Lykke M Ørnbjerg, Merete Lund Hetland, Lars Klareskog, Andrew Filer, Christopher D Buckley, Karim Raza, Torsten Witte, Reinhold E Schmidt, Jane Worthington

66 Citations (Scopus)

Abstract

Background: Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50-60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk. Objectives: To investigate recently identified RA susceptibility markers using cohorts from six European countries, and perform a meta-analysis including previously published results. Methods: 3311 DNA samples were collected from patients from six countries (UK, Germany, France, Greece, Sweden and Denmark). Genotype data or DNA samples for 3709 controls were collected from four countries (not Sweden or Denmark). Eighteen single nucleotide polymorphisms (SNPs) were genotyped using Sequenom MassArray technology. Samples with a >95% success rate and only those SNPs with a genotype success rate of >95% were included in the analysis. Scandinavian patient data were pooled and previously published Swedish control data were accessed as a comparison group. Meta-analysis was used to combine results from this study with all previously published data. Results: After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis. All 18 markers were associated with RA when previously published studies were incorporated in the analysis. Data from this study increased the significance for association with RA and nine markers. Conclusions: In a large European RA cohort further evidence for the association of 18 markers with RA development has been obtained.

Original language	English
Journal	Annals of the Rheumatic Diseases
Volume	69
Issue number	8
Pages (from-to)	1548-53
Number of pages	6
ISSN	0003-4967
DOIs	https://doi.org/10.1136/ard.2009.121020
Publication status	Published - 1 Aug 2010

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Plant, D., Flynn, E., Mbarek, H., Dieudé, P., Cornelis, F., Arlestig, L., Dahlqvist, S. R., Goulielmos, G., Boumpas, D. T., Sidiropoulos, P., Johansen, J. S., Ørnbjerg, L. M., Hetland, M. L., Klareskog, L., Filer, A., Buckley, C. D., Raza, K., Witte, T., Schmidt, R. E., & Worthington, J. (2010). Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers. Annals of the Rheumatic Diseases, 69(8), 1548-53. https://doi.org/10.1136/ard.2009.121020

Plant, D, Flynn, E, Mbarek, H, Dieudé, P, Cornelis, F, Arlestig, L, Dahlqvist, SR, Goulielmos, G, Boumpas, DT, Sidiropoulos, P, Johansen, JS, Ørnbjerg, LM, Hetland, ML, Klareskog, L, Filer, A, Buckley, CD, Raza, K, Witte, T, Schmidt, RE & Worthington, J 2010, 'Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers', Annals of the Rheumatic Diseases, vol. 69, no. 8, pp. 1548-53. https://doi.org/10.1136/ard.2009.121020

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title = "Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers",

abstract = "Background: Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50-60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk. Objectives: To investigate recently identified RA susceptibility markers using cohorts from six European countries, and perform a meta-analysis including previously published results. Methods: 3311 DNA samples were collected from patients from six countries (UK, Germany, France, Greece, Sweden and Denmark). Genotype data or DNA samples for 3709 controls were collected from four countries (not Sweden or Denmark). Eighteen single nucleotide polymorphisms (SNPs) were genotyped using Sequenom MassArray technology. Samples with a >95% success rate and only those SNPs with a genotype success rate of >95% were included in the analysis. Scandinavian patient data were pooled and previously published Swedish control data were accessed as a comparison group. Meta-analysis was used to combine results from this study with all previously published data. Results: After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis. All 18 markers were associated with RA when previously published studies were incorporated in the analysis. Data from this study increased the significance for association with RA and nine markers. Conclusions: In a large European RA cohort further evidence for the association of 18 markers with RA development has been obtained.",

author = "Darren Plant and Edward Flynn and Hamdi Mbarek and Philippe Dieud{\'e} and Fran{\c c}ois Cornelis and Lisbeth Arlestig and Dahlqvist, {Solbritt Rantap{\"a}{\"a}} and George Goulielmos and Boumpas, {Dimitrios T} and Prodromos Sidiropoulos and Johansen, {Julia S} and {\O}rnbjerg, {Lykke M} and Hetland, {Merete Lund} and Lars Klareskog and Andrew Filer and Buckley, {Christopher D} and Karim Raza and Torsten Witte and Schmidt, {Reinhold E} and Jane Worthington",

year = "2010",

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doi = "http://dx.doi.org/10.1136/ard.2009.121020",

language = "English",

volume = "69",

pages = "1548--53",

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TY - JOUR

T1 - Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers

AU - Plant, Darren

AU - Flynn, Edward

AU - Mbarek, Hamdi

AU - Dieudé, Philippe

AU - Cornelis, François

AU - Arlestig, Lisbeth

AU - Dahlqvist, Solbritt Rantapää

AU - Goulielmos, George

AU - Boumpas, Dimitrios T

AU - Sidiropoulos, Prodromos

AU - Johansen, Julia S

AU - Ørnbjerg, Lykke M

AU - Hetland, Merete Lund

AU - Klareskog, Lars

AU - Filer, Andrew

AU - Buckley, Christopher D

AU - Raza, Karim

AU - Witte, Torsten

AU - Schmidt, Reinhold E

AU - Worthington, Jane

PY - 2010/8/1

Y1 - 2010/8/1

N2 - Background: Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50-60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk. Objectives: To investigate recently identified RA susceptibility markers using cohorts from six European countries, and perform a meta-analysis including previously published results. Methods: 3311 DNA samples were collected from patients from six countries (UK, Germany, France, Greece, Sweden and Denmark). Genotype data or DNA samples for 3709 controls were collected from four countries (not Sweden or Denmark). Eighteen single nucleotide polymorphisms (SNPs) were genotyped using Sequenom MassArray technology. Samples with a >95% success rate and only those SNPs with a genotype success rate of >95% were included in the analysis. Scandinavian patient data were pooled and previously published Swedish control data were accessed as a comparison group. Meta-analysis was used to combine results from this study with all previously published data. Results: After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis. All 18 markers were associated with RA when previously published studies were incorporated in the analysis. Data from this study increased the significance for association with RA and nine markers. Conclusions: In a large European RA cohort further evidence for the association of 18 markers with RA development has been obtained.

AB - Background: Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50-60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk. Objectives: To investigate recently identified RA susceptibility markers using cohorts from six European countries, and perform a meta-analysis including previously published results. Methods: 3311 DNA samples were collected from patients from six countries (UK, Germany, France, Greece, Sweden and Denmark). Genotype data or DNA samples for 3709 controls were collected from four countries (not Sweden or Denmark). Eighteen single nucleotide polymorphisms (SNPs) were genotyped using Sequenom MassArray technology. Samples with a >95% success rate and only those SNPs with a genotype success rate of >95% were included in the analysis. Scandinavian patient data were pooled and previously published Swedish control data were accessed as a comparison group. Meta-analysis was used to combine results from this study with all previously published data. Results: After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis. All 18 markers were associated with RA when previously published studies were incorporated in the analysis. Data from this study increased the significance for association with RA and nine markers. Conclusions: In a large European RA cohort further evidence for the association of 18 markers with RA development has been obtained.

U2 - http://dx.doi.org/10.1136/ard.2009.121020

DO - http://dx.doi.org/10.1136/ard.2009.121020

M3 - Journal article

SN - 0003-4967

VL - 69

SP - 1548

EP - 1553

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 8

ER -

Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers

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