Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23

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Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23. / Wellcome Trust Case Control Consortium; YEAR consortium.

In: Human Molecular Genetics, Vol. 18, No. 14, 15.07.2009, p. 2693-2699.

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Wellcome Trust Case Control Consortium & YEAR consortium 2009, 'Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23', Human Molecular Genetics, vol. 18, no. 14, pp. 2693-2699. https://doi.org/10.1093/hmg/ddp193

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Wellcome Trust Case Control Consortium ; YEAR consortium. / Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 14. pp. 2693-2699.

Bibtex

@article{34cb265a4c294f11bdc5806944a33157,
title = "Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23",
abstract = "The most consistent finding derived from the WTCCC GWAS for rheumatoid arthritis (RA) was association to a SNP at 6q23. We performed a fine-mapping of the region in order to search the 6q23 region for additional disease variants. 3962 RA patients and 3531 healthy controls were included in the study. We found 18 SNPs associated with RA. The SNP showing the strongest association was rs6920220 [P = 2.6 x 10(-6), OR (95% CI) 1.22 (1.13-1.33)]. The next most strongly associated SNP was rs13207033 [P = 0.0001, OR (95% CI) 0.86 (0.8-0.93)] which was perfectly correlated with rs10499194, a SNP previously associated with RA in a US/European series. Additionally, we found a number of new potential RA markers, including rs5029937, located in the intron 2 of TNFAIP3. Of the 18 associated SNPs, three polymorphisms, rs6920220, rs13207033 and rs5029937, remained significant after conditional logistic regression analysis. The combination of the carriage of both risk alleles of rs6920220 and rs5029937 together with the absence of the protective allele of rs13207033 was strongly associated with RA when compared with carriage of none [OR of 1.86 (95% CI) (1.51-2.29)]. This equates to an effect size of 1.50 (95% CI 1.21-1.85) compared with controls and is higher than that obtained for any SNP individually. This is the first study to show that the confirmed loci from the GWA studies, that confer only a modest effect size, could harbour a significantly greater effect once the effect of additional risk variants are accounted for.",
author = "Gisela Orozco and Anne Hinks and Steve Eyre and Xiayi Ke and Gibbons, {Laura J.} and John Bowes and Edward Flynn and Paul Martin and {Wellcome Trust Case Control Consortium} and {YEAR consortium} and Wilson, {Anthony G.} and Bax, {Deborah E.} and Morgan, {Ann W.} and Paul Emery and Sophia Steer and Lynne Hocking and Reid, {David M.} and Paul Wordsworth and Pille Harrison and Wendy Thomson and Anne Barton and Jane Worthington and Jayne Franklyn",
year = "2009",
month = jul,
day = "15",
doi = "10.1093/hmg/ddp193",
language = "English",
volume = "18",
pages = "2693--2699",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "14",

}

RIS

TY - JOUR

T1 - Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23

AU - Orozco, Gisela

AU - Hinks, Anne

AU - Eyre, Steve

AU - Ke, Xiayi

AU - Gibbons, Laura J.

AU - Bowes, John

AU - Flynn, Edward

AU - Martin, Paul

AU - Wellcome Trust Case Control Consortium

AU - YEAR consortium

AU - Wilson, Anthony G.

AU - Bax, Deborah E.

AU - Morgan, Ann W.

AU - Emery, Paul

AU - Steer, Sophia

AU - Hocking, Lynne

AU - Reid, David M.

AU - Wordsworth, Paul

AU - Harrison, Pille

AU - Thomson, Wendy

AU - Barton, Anne

AU - Worthington, Jane

AU - Franklyn, Jayne

PY - 2009/7/15

Y1 - 2009/7/15

N2 - The most consistent finding derived from the WTCCC GWAS for rheumatoid arthritis (RA) was association to a SNP at 6q23. We performed a fine-mapping of the region in order to search the 6q23 region for additional disease variants. 3962 RA patients and 3531 healthy controls were included in the study. We found 18 SNPs associated with RA. The SNP showing the strongest association was rs6920220 [P = 2.6 x 10(-6), OR (95% CI) 1.22 (1.13-1.33)]. The next most strongly associated SNP was rs13207033 [P = 0.0001, OR (95% CI) 0.86 (0.8-0.93)] which was perfectly correlated with rs10499194, a SNP previously associated with RA in a US/European series. Additionally, we found a number of new potential RA markers, including rs5029937, located in the intron 2 of TNFAIP3. Of the 18 associated SNPs, three polymorphisms, rs6920220, rs13207033 and rs5029937, remained significant after conditional logistic regression analysis. The combination of the carriage of both risk alleles of rs6920220 and rs5029937 together with the absence of the protective allele of rs13207033 was strongly associated with RA when compared with carriage of none [OR of 1.86 (95% CI) (1.51-2.29)]. This equates to an effect size of 1.50 (95% CI 1.21-1.85) compared with controls and is higher than that obtained for any SNP individually. This is the first study to show that the confirmed loci from the GWA studies, that confer only a modest effect size, could harbour a significantly greater effect once the effect of additional risk variants are accounted for.

AB - The most consistent finding derived from the WTCCC GWAS for rheumatoid arthritis (RA) was association to a SNP at 6q23. We performed a fine-mapping of the region in order to search the 6q23 region for additional disease variants. 3962 RA patients and 3531 healthy controls were included in the study. We found 18 SNPs associated with RA. The SNP showing the strongest association was rs6920220 [P = 2.6 x 10(-6), OR (95% CI) 1.22 (1.13-1.33)]. The next most strongly associated SNP was rs13207033 [P = 0.0001, OR (95% CI) 0.86 (0.8-0.93)] which was perfectly correlated with rs10499194, a SNP previously associated with RA in a US/European series. Additionally, we found a number of new potential RA markers, including rs5029937, located in the intron 2 of TNFAIP3. Of the 18 associated SNPs, three polymorphisms, rs6920220, rs13207033 and rs5029937, remained significant after conditional logistic regression analysis. The combination of the carriage of both risk alleles of rs6920220 and rs5029937 together with the absence of the protective allele of rs13207033 was strongly associated with RA when compared with carriage of none [OR of 1.86 (95% CI) (1.51-2.29)]. This equates to an effect size of 1.50 (95% CI 1.21-1.85) compared with controls and is higher than that obtained for any SNP individually. This is the first study to show that the confirmed loci from the GWA studies, that confer only a modest effect size, could harbour a significantly greater effect once the effect of additional risk variants are accounted for.

U2 - 10.1093/hmg/ddp193

DO - 10.1093/hmg/ddp193

M3 - Article

C2 - 19417005

VL - 18

SP - 2693

EP - 2699

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 14

ER -