Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci

John B Harley; Marta E Alarcón-Riquelme; Lindsey A Criswell; Chaim O Jacob; Robert P Kimberly; Kathy L Moser; Betty P Tsao; Timothy J Vyse; Carl D Langefeld; Swapan K Nath; Joel M Guthridge; Beth L Cobb; Daniel B Mirel; Miranda C Marion; Adrienne H Williams; Jasmin Divers; Wei Wang; Summer G Frank; Bahram Namjou; Stacey B Gabriel; Annette T Lee; Peter K Gregersen; Timothy W Behrens; Kimberly E Taylor; Maria Michelle Fernando; Raphael Zidovetzki; Patrick M Gaffney; Jeffrey C Edberg; John D Rioux; Joshua O Ojwang; Judith A James; Joan T Merrill; Gary S Gilkeson; Michael F Seldin; Hong Yin; Emily C Baechler; Quan-Zhen Li; Edward K Wakeland; Gail R Bruner; Kenneth M Kaufman; Jennifer A Kelly; International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN)

doi:10.1038/ng.81

Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci

John B Harley, Marta E Alarcón-Riquelme, Lindsey A Criswell, Chaim O Jacob, Robert P Kimberly, Kathy L Moser, Betty P Tsao, Timothy J Vyse, Carl D Langefeld, Swapan K Nath, Joel M Guthridge, Beth L Cobb, Daniel B Mirel, Miranda C Marion, Adrienne H Williams, Jasmin Divers, Wei Wang, Summer G Frank, Bahram Namjou, Stacey B GabrielAnnette T Lee, Peter K Gregersen, Timothy W Behrens, Kimberly E Taylor, Maria Michelle Fernando, Raphael Zidovetzki, Patrick M Gaffney, Jeffrey C Edberg, John D Rioux, Joshua O Ojwang, Judith A James, Joan T Merrill, Gary S Gilkeson, Michael F Seldin, Hong Yin, Emily C Baechler, Quan-Zhen Li, Edward K Wakeland, Gail R Bruner, Kenneth M Kaufman, Jennifer A Kelly, International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN)

Medical & Molecular Genetics

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

1151 Citations (Scopus)

Abstract

Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) <P(overall) <1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P <1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P <2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.

Original language	English
Pages (from-to)	204-210
Number of pages	7
Journal	Nature Genetics
Volume	40
Issue number	2
DOIs	https://doi.org/10.1038/ng.81
Publication status	Published - Feb 2008

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Harley, J. B., Alarcón-Riquelme, M. E., Criswell, L. A., Jacob, C. O., Kimberly, R. P., Moser, K. L., Tsao, B. P., Vyse, T. J., Langefeld, C. D., Nath, S. K., Guthridge, J. M., Cobb, B. L., Mirel, D. B., Marion, M. C., Williams, A. H., Divers, J., Wang, W., Frank, S. G., Namjou, B., ... International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN) (2008). Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nature Genetics, 40(2), 204-210. https://doi.org/10.1038/ng.81

@article{15ebe20cdf194f32b266d4bae3fbc908,

title = "Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci",

abstract = "Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) or =9 other loci (P <2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.",

author = "Harley, {John B} and Alarc{\'o}n-Riquelme, {Marta E} and Criswell, {Lindsey A} and Jacob, {Chaim O} and Kimberly, {Robert P} and Moser, {Kathy L} and Tsao, {Betty P} and Vyse, {Timothy J} and Langefeld, {Carl D} and Nath, {Swapan K} and Guthridge, {Joel M} and Cobb, {Beth L} and Mirel, {Daniel B} and Marion, {Miranda C} and Williams, {Adrienne H} and Jasmin Divers and Wei Wang and Frank, {Summer G} and Bahram Namjou and Gabriel, {Stacey B} and Lee, {Annette T} and Gregersen, {Peter K} and Behrens, {Timothy W} and Taylor, {Kimberly E} and Fernando, {Maria Michelle} and Raphael Zidovetzki and Gaffney, {Patrick M} and Edberg, {Jeffrey C} and Rioux, {John D} and Ojwang, {Joshua O} and James, {Judith A} and Merrill, {Joan T} and Gilkeson, {Gary S} and Seldin, {Michael F} and Hong Yin and Baechler, {Emily C} and Quan-Zhen Li and Wakeland, {Edward K} and Bruner, {Gail R} and Kaufman, {Kenneth M} and Kelly, {Jennifer A} and {International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN)}",

year = "2008",

month = feb,

doi = "10.1038/ng.81",

language = "English",

volume = "40",

pages = "204--210",

journal = "Nature Genetics",

issn = "1546-1718",

publisher = "Nature Research",

number = "2",

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Harley, JB, Alarcón-Riquelme, ME, Criswell, LA, Jacob, CO, Kimberly, RP, Moser, KL, Tsao, BP, Vyse, TJ, Langefeld, CD, Nath, SK, Guthridge, JM, Cobb, BL, Mirel, DB, Marion, MC, Williams, AH, Divers, J, Wang, W, Frank, SG, Namjou, B, Gabriel, SB, Lee, AT, Gregersen, PK, Behrens, TW, Taylor, KE, Fernando, MM, Zidovetzki, R, Gaffney, PM, Edberg, JC, Rioux, JD, Ojwang, JO, James, JA, Merrill, JT, Gilkeson, GS, Seldin, MF, Yin, H, Baechler, EC, Li, Q-Z, Wakeland, EK, Bruner, GR, Kaufman, KM, Kelly, JA & International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN) 2008, 'Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci', Nature Genetics, vol. 40, no. 2, pp. 204-210. https://doi.org/10.1038/ng.81

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T1 - Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci

AU - Harley, John B

AU - Alarcón-Riquelme, Marta E

AU - Criswell, Lindsey A

AU - Jacob, Chaim O

AU - Kimberly, Robert P

AU - Moser, Kathy L

AU - Tsao, Betty P

AU - Vyse, Timothy J

AU - Langefeld, Carl D

AU - Nath, Swapan K

AU - Guthridge, Joel M

AU - Cobb, Beth L

AU - Mirel, Daniel B

AU - Marion, Miranda C

AU - Williams, Adrienne H

AU - Divers, Jasmin

AU - Wang, Wei

AU - Frank, Summer G

AU - Namjou, Bahram

AU - Gabriel, Stacey B

AU - Lee, Annette T

AU - Gregersen, Peter K

AU - Behrens, Timothy W

AU - Taylor, Kimberly E

AU - Fernando, Maria Michelle

AU - Zidovetzki, Raphael

AU - Gaffney, Patrick M

AU - Edberg, Jeffrey C

AU - Rioux, John D

AU - Ojwang, Joshua O

AU - James, Judith A

AU - Merrill, Joan T

AU - Gilkeson, Gary S

AU - Seldin, Michael F

AU - Yin, Hong

AU - Baechler, Emily C

AU - Li, Quan-Zhen

AU - Wakeland, Edward K

AU - Bruner, Gail R

AU - Kaufman, Kenneth M

AU - Kelly, Jennifer A

AU - International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN)

PY - 2008/2

Y1 - 2008/2

N2 - Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) or =9 other loci (P <2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.

AB - Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) or =9 other loci (P <2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.

U2 - 10.1038/ng.81

DO - 10.1038/ng.81

M3 - Article

C2 - 18204446

SN - 1546-1718

VL - 40

SP - 204

EP - 210

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci

Abstract

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