Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study

Gisela Orozco; Sebastien Viatte; John Bowes; Paul Martin; Anthony G Wilson; Ann W Morgan; Sophia Steer; Paul Wordsworth; Lynne Hocking; Anne Barton; Jane Worthington; Stephen Eyre; UK Rheumatoid Arthritis Genetics Consortium

doi:10.1002/art.38196

Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study

Gisela Orozco, Sebastien Viatte, John Bowes, Paul Martin, Anthony G Wilson, Ann W Morgan, Sophia Steer, Paul Wordsworth, Lynne Hocking, Anne Barton, Jane Worthington, Stephen Eyre, UK Rheumatoid Arthritis Genetics Consortium

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Abstract

OBJECTIVE: The number of confirmed rheumatoid arthritis (RA) loci currently stands at 32, but many lines of evidence indicate that expansion of existing genome-wide association studies (GWAS) enhances the power to detect additional loci. This study was undertaken to extend our previous RA GWAS in a UK cohort, adding more independent RA cases and healthy controls, with the aim of detecting novel association signals for susceptibility to RA in a homogeneous UK cohort.

METHODS: A total of 3,223 UK RA cases and 5,272 UK controls were available for association analyses, with the extension adding 1,361 cases and 2,334 controls to the original GWAS data set. The genotype data for all RA cases were imputed using the Impute program version 2. After stringent quality control thresholds were applied, 3,034 cases and 5,271 controls (1,831,729 single-nucleotide polymorphisms [SNPs]) were available for analysis. Association testing was performed using Plink software.

RESULTS: The analyses indicated a suggestive association with susceptibility to RA (P < 0.0001) for 6 novel RA loci that have been previously found to be associated with other autoimmune diseases; these 6 SNPs were genotyped in independent samples. Two of the associated loci were validated, one of which was associated with RA at genome-wide levels of significance in the combined analysis, identifying a novel RA locus at 22q12 (P = 6.9 × 10(-9) ). In addition, most of the previously known RA susceptibility loci were confirmed to be associated with RA, and for 16 of the loci, the strength of the association was increased.

CONCLUSION: This study identified a new RA locus mapping to 22q12. These results support the notion that increasing the power of GWAS enhances novel gene discovery.

Original language	English
Pages (from-to)	24-30
Number of pages	7
Journal	Arthritis & Rheumatology
Volume	66
Issue number	1
Early online date	30 Dec 2013
DOIs	https://doi.org/10.1002/art.38196
Publication status	Published - Jan 2014

Keywords

Arthritis, Rheumatoid
Case-Control Studies
Chromosomes, Human, Pair 22
Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Great Britain
Humans
Polymorphism, Single Nucleotide

UN SDGs

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10.1002/art.38196

Novel Rheumatoid Arthritis Susceptibility Locus at 22q12
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Orozco, G., Viatte, S., Bowes, J., Martin, P., Wilson, A. G., Morgan, A. W., Steer, S., Wordsworth, P., Hocking, L., Barton, A., Worthington, J., Eyre, S., & UK Rheumatoid Arthritis Genetics Consortium (2014). Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study. Arthritis & Rheumatology, 66(1), 24-30. https://doi.org/10.1002/art.38196

Orozco, G, Viatte, S, Bowes, J, Martin, P, Wilson, AG, Morgan, AW, Steer, S, Wordsworth, P, Hocking, L, Barton, A, Worthington, J, Eyre, S & UK Rheumatoid Arthritis Genetics Consortium 2014, 'Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study', Arthritis & Rheumatology, vol. 66, no. 1, pp. 24-30. https://doi.org/10.1002/art.38196

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abstract = "OBJECTIVE: The number of confirmed rheumatoid arthritis (RA) loci currently stands at 32, but many lines of evidence indicate that expansion of existing genome-wide association studies (GWAS) enhances the power to detect additional loci. This study was undertaken to extend our previous RA GWAS in a UK cohort, adding more independent RA cases and healthy controls, with the aim of detecting novel association signals for susceptibility to RA in a homogeneous UK cohort.METHODS: A total of 3,223 UK RA cases and 5,272 UK controls were available for association analyses, with the extension adding 1,361 cases and 2,334 controls to the original GWAS data set. The genotype data for all RA cases were imputed using the Impute program version 2. After stringent quality control thresholds were applied, 3,034 cases and 5,271 controls (1,831,729 single-nucleotide polymorphisms [SNPs]) were available for analysis. Association testing was performed using Plink software.RESULTS: The analyses indicated a suggestive association with susceptibility to RA (P < 0.0001) for 6 novel RA loci that have been previously found to be associated with other autoimmune diseases; these 6 SNPs were genotyped in independent samples. Two of the associated loci were validated, one of which was associated with RA at genome-wide levels of significance in the combined analysis, identifying a novel RA locus at 22q12 (P = 6.9 × 10(-9) ). In addition, most of the previously known RA susceptibility loci were confirmed to be associated with RA, and for 16 of the loci, the strength of the association was increased.CONCLUSION: This study identified a new RA locus mapping to 22q12. These results support the notion that increasing the power of GWAS enhances novel gene discovery.",

keywords = "Arthritis, Rheumatoid, Case-Control Studies, Chromosomes, Human, Pair 22, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Great Britain, Humans, Polymorphism, Single Nucleotide",

author = "Gisela Orozco and Sebastien Viatte and John Bowes and Paul Martin and Wilson, {Anthony G} and Morgan, {Ann W} and Sophia Steer and Paul Wordsworth and Lynne Hocking and Anne Barton and Jane Worthington and Stephen Eyre and {UK Rheumatoid Arthritis Genetics Consortium}",

note = "{\textcopyright} 2014 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.",

year = "2014",

month = jan,

doi = "10.1002/art.38196",

language = "English",

volume = "66",

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T1 - Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study

AU - Orozco, Gisela

AU - Viatte, Sebastien

AU - Bowes, John

AU - Martin, Paul

AU - Wilson, Anthony G

AU - Morgan, Ann W

AU - Steer, Sophia

AU - Wordsworth, Paul

AU - Hocking, Lynne

AU - Barton, Anne

AU - Worthington, Jane

AU - Eyre, Stephen

AU - UK Rheumatoid Arthritis Genetics Consortium

PY - 2014/1

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N2 - OBJECTIVE: The number of confirmed rheumatoid arthritis (RA) loci currently stands at 32, but many lines of evidence indicate that expansion of existing genome-wide association studies (GWAS) enhances the power to detect additional loci. This study was undertaken to extend our previous RA GWAS in a UK cohort, adding more independent RA cases and healthy controls, with the aim of detecting novel association signals for susceptibility to RA in a homogeneous UK cohort.METHODS: A total of 3,223 UK RA cases and 5,272 UK controls were available for association analyses, with the extension adding 1,361 cases and 2,334 controls to the original GWAS data set. The genotype data for all RA cases were imputed using the Impute program version 2. After stringent quality control thresholds were applied, 3,034 cases and 5,271 controls (1,831,729 single-nucleotide polymorphisms [SNPs]) were available for analysis. Association testing was performed using Plink software.RESULTS: The analyses indicated a suggestive association with susceptibility to RA (P < 0.0001) for 6 novel RA loci that have been previously found to be associated with other autoimmune diseases; these 6 SNPs were genotyped in independent samples. Two of the associated loci were validated, one of which was associated with RA at genome-wide levels of significance in the combined analysis, identifying a novel RA locus at 22q12 (P = 6.9 × 10(-9) ). In addition, most of the previously known RA susceptibility loci were confirmed to be associated with RA, and for 16 of the loci, the strength of the association was increased.CONCLUSION: This study identified a new RA locus mapping to 22q12. These results support the notion that increasing the power of GWAS enhances novel gene discovery.

AB - OBJECTIVE: The number of confirmed rheumatoid arthritis (RA) loci currently stands at 32, but many lines of evidence indicate that expansion of existing genome-wide association studies (GWAS) enhances the power to detect additional loci. This study was undertaken to extend our previous RA GWAS in a UK cohort, adding more independent RA cases and healthy controls, with the aim of detecting novel association signals for susceptibility to RA in a homogeneous UK cohort.METHODS: A total of 3,223 UK RA cases and 5,272 UK controls were available for association analyses, with the extension adding 1,361 cases and 2,334 controls to the original GWAS data set. The genotype data for all RA cases were imputed using the Impute program version 2. After stringent quality control thresholds were applied, 3,034 cases and 5,271 controls (1,831,729 single-nucleotide polymorphisms [SNPs]) were available for analysis. Association testing was performed using Plink software.RESULTS: The analyses indicated a suggestive association with susceptibility to RA (P < 0.0001) for 6 novel RA loci that have been previously found to be associated with other autoimmune diseases; these 6 SNPs were genotyped in independent samples. Two of the associated loci were validated, one of which was associated with RA at genome-wide levels of significance in the combined analysis, identifying a novel RA locus at 22q12 (P = 6.9 × 10(-9) ). In addition, most of the previously known RA susceptibility loci were confirmed to be associated with RA, and for 16 of the loci, the strength of the association was increased.CONCLUSION: This study identified a new RA locus mapping to 22q12. These results support the notion that increasing the power of GWAS enhances novel gene discovery.

KW - Arthritis, Rheumatoid

KW - Case-Control Studies

KW - Chromosomes, Human, Pair 22

KW - Gene Frequency

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Great Britain

KW - Humans

KW - Polymorphism, Single Nucleotide

U2 - 10.1002/art.38196

DO - 10.1002/art.38196

M3 - Article

C2 - 24449572

VL - 66

SP - 24

EP - 30

JO - Arthritis & Rheumatology

JF - Arthritis & Rheumatology

SN - 2326-5191

IS - 1

ER -

Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study

Abstract

Keywords

UN SDGs

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