A nonsynonymous functional variant in integrin-αM (encoded by ITGAM) is associated with systemic lupus erythematosus

Swapan K. Nath; Shizhong Han; Xana Kim-Howard; Jennifer A. Kelly; Parvathi Viswanathan; Gary S. Gilkeson; Wei Chen; Cheng Zhu; Rodger P. McEver; Robert P. Kimberly; Marta E. Alarcón-Riquelme; Timothy J. Vyse; Quan Zhen Li; Edward K. Wakeland; Joan T. Merrill; Judith A. James; Kenneth M. Kaufman; Joel M. Guthridge; John B. Harley

doi:10.1038/ng.71

A nonsynonymous functional variant in integrin-α_M (encoded by ITGAM) is associated with systemic lupus erythematosus

Swapan K. Nath, Shizhong Han, Xana Kim-Howard, Jennifer A. Kelly, Parvathi Viswanathan, Gary S. Gilkeson, Wei Chen, Cheng Zhu, Rodger P. McEver, Robert P. Kimberly, Marta E. Alarcón-Riquelme, Timothy J. Vyse, Quan Zhen Li, Edward K. Wakeland, Joan T. Merrill, Judith A. James, Kenneth M. Kaufman, Joel M. Guthridge, John B. Harley

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Abstract

We identified and replicated an association between ITGAM (CD11b) at 16p11.2 and risk of systemic lupus erythematosus (SLE) in 3,818 individuals of European descent. The strongest association was at a nonsynonymous SNP, rs1143679 (P = 1.7 × 10^-17, odds ratio = 1.78). We further replicated this association in two independent samples of individuals of African descent (P = 0.0002 and 0.003; overall meta-analysis P = 6.9 × 10 ^-22). The genetic association between ITGAM and SLE implicates the α_Mβ₂-integrin adhesion pathway in disease development.

Original language	English (US)
Pages (from-to)	152-154
Number of pages	3
Journal	Nature genetics
Volume	40
Issue number	2
DOIs	https://doi.org/10.1038/ng.71
State	Published - Feb 2008

ASJC Scopus subject areas

Genetics

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Nath, S. K., Han, S., Kim-Howard, X., Kelly, J. A., Viswanathan, P., Gilkeson, G. S., Chen, W., Zhu, C., McEver, R. P., Kimberly, R. P., Alarcón-Riquelme, M. E., Vyse, T. J., Li, Q. Z., Wakeland, E. K., Merrill, J. T., James, J. A., Kaufman, K. M., Guthridge, J. M., & Harley, J. B. (2008). A nonsynonymous functional variant in integrin-α_M (encoded by ITGAM) is associated with systemic lupus erythematosus. Nature genetics, 40(2), 152-154. https://doi.org/10.1038/ng.71

Nath, SK, Han, S, Kim-Howard, X, Kelly, JA, Viswanathan, P, Gilkeson, GS, Chen, W, Zhu, C, McEver, RP, Kimberly, RP, Alarcón-Riquelme, ME, Vyse, TJ, Li, QZ, Wakeland, EK, Merrill, JT, James, JA, Kaufman, KM, Guthridge, JM & Harley, JB 2008, 'A nonsynonymous functional variant in integrin-α_M (encoded by ITGAM) is associated with systemic lupus erythematosus', Nature genetics, vol. 40, no. 2, pp. 152-154. https://doi.org/10.1038/ng.71

@article{fc15a6c4ead246faa7fe89da70352883,

title = "A nonsynonymous functional variant in integrin-αM (encoded by ITGAM) is associated with systemic lupus erythematosus",

abstract = "We identified and replicated an association between ITGAM (CD11b) at 16p11.2 and risk of systemic lupus erythematosus (SLE) in 3,818 individuals of European descent. The strongest association was at a nonsynonymous SNP, rs1143679 (P = 1.7 × 10-17, odds ratio = 1.78). We further replicated this association in two independent samples of individuals of African descent (P = 0.0002 and 0.003; overall meta-analysis P = 6.9 × 10 -22). The genetic association between ITGAM and SLE implicates the αMβ2-integrin adhesion pathway in disease development.",

author = "Nath, {Swapan K.} and Shizhong Han and Xana Kim-Howard and Kelly, {Jennifer A.} and Parvathi Viswanathan and Gilkeson, {Gary S.} and Wei Chen and Cheng Zhu and McEver, {Rodger P.} and Kimberly, {Robert P.} and Alarc{\'o}n-Riquelme, {Marta E.} and Vyse, {Timothy J.} and Li, {Quan Zhen} and Wakeland, {Edward K.} and Merrill, {Joan T.} and James, {Judith A.} and Kaufman, {Kenneth M.} and Guthridge, {Joel M.} and Harley, {John B.}",

note = "Funding Information: We are grateful to the affected individuals and their families for their cooperation and blood samples. This work would also not have been possible without the support of the all the LFRR staff, headed by LFRR director G. Bruner. We also acknowledge the contributions of sample from our collaborators, especially P. Gregersen, L. Barcelos, J. Oksenberg, J. Edberg, the PROFILE cohort (G. Alarcon, M. Petri, R. Ramsey-Goldman and J. Reveille), P. Gaffney and K. Moser. This work was supported by supported by the US National Institutes of Health (grants AR048928, AI063622, RR020143, AR049084, AI24717, AR42460, AR048940, HL 34363, AI053747, AR12253, DE15223, RR01577, RR14467, AI31584 and AI044902), the Alliance for Lupus Research, a Mary Kirkland Scholarship and the US Department of Veterans Affairs.",

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AU - Nath, Swapan K.

AU - Han, Shizhong

AU - Kim-Howard, Xana

AU - Kelly, Jennifer A.

AU - Viswanathan, Parvathi

AU - Gilkeson, Gary S.

AU - Chen, Wei

AU - Zhu, Cheng

AU - McEver, Rodger P.

AU - Kimberly, Robert P.

AU - Alarcón-Riquelme, Marta E.

AU - Vyse, Timothy J.

AU - Li, Quan Zhen

AU - Wakeland, Edward K.

AU - Merrill, Joan T.

AU - James, Judith A.

AU - Kaufman, Kenneth M.

AU - Guthridge, Joel M.

AU - Harley, John B.

N1 - Funding Information: We are grateful to the affected individuals and their families for their cooperation and blood samples. This work would also not have been possible without the support of the all the LFRR staff, headed by LFRR director G. Bruner. We also acknowledge the contributions of sample from our collaborators, especially P. Gregersen, L. Barcelos, J. Oksenberg, J. Edberg, the PROFILE cohort (G. Alarcon, M. Petri, R. Ramsey-Goldman and J. Reveille), P. Gaffney and K. Moser. This work was supported by supported by the US National Institutes of Health (grants AR048928, AI063622, RR020143, AR049084, AI24717, AR42460, AR048940, HL 34363, AI053747, AR12253, DE15223, RR01577, RR14467, AI31584 and AI044902), the Alliance for Lupus Research, a Mary Kirkland Scholarship and the US Department of Veterans Affairs.

PY - 2008/2

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N2 - We identified and replicated an association between ITGAM (CD11b) at 16p11.2 and risk of systemic lupus erythematosus (SLE) in 3,818 individuals of European descent. The strongest association was at a nonsynonymous SNP, rs1143679 (P = 1.7 × 10-17, odds ratio = 1.78). We further replicated this association in two independent samples of individuals of African descent (P = 0.0002 and 0.003; overall meta-analysis P = 6.9 × 10 -22). The genetic association between ITGAM and SLE implicates the αMβ2-integrin adhesion pathway in disease development.

AB - We identified and replicated an association between ITGAM (CD11b) at 16p11.2 and risk of systemic lupus erythematosus (SLE) in 3,818 individuals of European descent. The strongest association was at a nonsynonymous SNP, rs1143679 (P = 1.7 × 10-17, odds ratio = 1.78). We further replicated this association in two independent samples of individuals of African descent (P = 0.0002 and 0.003; overall meta-analysis P = 6.9 × 10 -22). The genetic association between ITGAM and SLE implicates the αMβ2-integrin adhesion pathway in disease development.

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A nonsynonymous functional variant in integrin-α_M (encoded by ITGAM) is associated with systemic lupus erythematosus

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