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.
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Acknowledgements
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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S.K.N. participated in the conception, design and coordination of the study, directed the whole project and drafted the manuscript. S.H. and X.K.-H. managed the genotyping data and analyzed the data. P.V. did the genotyping for the trio data. G.S.G., R.P.K., M.E.A.-R., J.T.M. and T.J.V. provided samples used in this study. J.M.G., R.P.M., C.Z. and W.C. provided protein structural analysis and functional predictions. K.M.K., E.K.W., J.A.K. and Q.-Z.L. were responsible for overseeing the genotyping and quality control of the actual genotype data. J.A.J. and J.M.G. participated in collecting samples and designing experiments and helped in drafting the manuscript. J.B.H. was responsible for making the DNA available and supervising the overall genotyping project. All authors contributed to the final manuscript.
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Nath, S., Han, S., Kim-Howard, X. et al. A nonsynonymous functional variant in integrin-αM (encoded by ITGAM) is associated with systemic lupus erythematosus. Nat Genet 40, 152–154 (2008). https://doi.org/10.1038/ng.71
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DOI: https://doi.org/10.1038/ng.71
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