Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency

Ricardo C. Ferreira; Qiang Pan-Hammarström; Robert R. Graham; Vesela Gateva; Gumersindo Fontán; Annette T. Lee; Ward Ortmann; Elena Urcelay; Miguel Fernández-Arquero; Concepción Núnez; Gudmundur Jorgensen; Björn R. Ludviksson; Sinikka Koskinen; Katri Haimila; Hilary F. Clark; Lars Klareskog; Peter K. Gregersen; Timothy W. Behrens; Lennart HammarströM

doi:10.1038/ng.644

Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency

Ricardo C. Ferreira, Qiang Pan-Hammarström, Robert R. Graham, Vesela Gateva, Gumersindo Fontán, Annette T. Lee, Ward Ortmann, Elena Urcelay, Miguel Fernández-Arquero, Concepción Núnez, Gudmundur Jorgensen, Björn R. Ludviksson, Sinikka Koskinen, Katri Haimila, Hilary F. Clark, Lars Klareskog, Peter K. Gregersen, Timothy W. Behrens^*, Lennart HammarströM

^*Corresponding author for this work

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

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Abstract

To understand the genetic predisposition to selective immunoglobulin A deficiency (IgAD), we performed a genome-wide association study in 430 affected individuals (cases) from Sweden and Iceland and 1, 090 ethnically matched controls, and we performed replication studies in two independent European cohorts. In addition to the known association of HLA with IgAD, we identified association with a nonsynonymous variant in IFIH1 (rs1990760G>A, P = 7.3 x 10^-10) which was previously associated with type 1 diabetes and systemic lupus erythematosus. Variants in CLEC16A, another known autoimmunity locus, showed suggestive evidence for association (rs6498142C>G, P = 1.8 x 10^-7), and 29 additional loci were identified with P < 5 x 10^-5. A survey in IgAD of 118 validated non-HLA autoimmunity loci indicated a significant enrichment for association with autoimmunity loci as compared to non-autoimmunity loci (P = 9.0 x 10^-4) or random SNPs across the genome (P < 0.0001). These findings support the hypothesis that autoimmune mechanisms may contribute to the pathogenesis of IgAD.

Original language	English
Pages (from-to)	777-782
Number of pages	6
Journal	Nature Genetics
Volume	42
Issue number	9
DOIs	https://doi.org/10.1038/ng.644
Publication status	Published - Sept 2010

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Ferreira, R. C., Pan-Hammarström, Q., Graham, R. R., Gateva, V., Fontán, G., Lee, A. T., Ortmann, W., Urcelay, E., Fernández-Arquero, M., Núnez, C., Jorgensen, G., Ludviksson, B. R., Koskinen, S., Haimila, K., Clark, H. F., Klareskog, L., Gregersen, P. K., Behrens, T. W., & HammarströM, L. (2010). Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency. Nature Genetics, 42(9), 777-782. https://doi.org/10.1038/ng.644

@article{0345833801f54cc4bb332de6ff6efffa,

title = "Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency",

abstract = "To understand the genetic predisposition to selective immunoglobulin A deficiency (IgAD), we performed a genome-wide association study in 430 affected individuals (cases) from Sweden and Iceland and 1, 090 ethnically matched controls, and we performed replication studies in two independent European cohorts. In addition to the known association of HLA with IgAD, we identified association with a nonsynonymous variant in IFIH1 (rs1990760G>A, P = 7.3 x 10-10) which was previously associated with type 1 diabetes and systemic lupus erythematosus. Variants in CLEC16A, another known autoimmunity locus, showed suggestive evidence for association (rs6498142C>G, P = 1.8 x 10-7), and 29 additional loci were identified with P < 5 x 10-5. A survey in IgAD of 118 validated non-HLA autoimmunity loci indicated a significant enrichment for association with autoimmunity loci as compared to non-autoimmunity loci (P = 9.0 x 10-4) or random SNPs across the genome (P < 0.0001). These findings support the hypothesis that autoimmune mechanisms may contribute to the pathogenesis of IgAD.",

author = "Ferreira, {Ricardo C.} and Qiang Pan-Hammarstr{\"o}m and Graham, {Robert R.} and Vesela Gateva and Gumersindo Font{\'a}n and Lee, {Annette T.} and Ward Ortmann and Elena Urcelay and Miguel Fern{\'a}ndez-Arquero and Concepci{\'o}n N{\'u}nez and Gudmundur Jorgensen and Ludviksson, {Bj{\"o}rn R.} and Sinikka Koskinen and Katri Haimila and Clark, {Hilary F.} and Lars Klareskog and Gregersen, {Peter K.} and Behrens, {Timothy W.} and Lennart Hammarstr{\"o}M",

year = "2010",

month = sep,

doi = "10.1038/ng.644",

language = "English",

volume = "42",

pages = "777--782",

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Ferreira, RC, Pan-Hammarström, Q, Graham, RR, Gateva, V, Fontán, G, Lee, AT, Ortmann, W, Urcelay, E, Fernández-Arquero, M, Núnez, C, Jorgensen, G, Ludviksson, BR, Koskinen, S, Haimila, K, Clark, HF, Klareskog, L, Gregersen, PK, Behrens, TW & HammarströM, L 2010, 'Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency', Nature Genetics, vol. 42, no. 9, pp. 777-782. https://doi.org/10.1038/ng.644

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AU - Pan-Hammarström, Qiang

AU - Graham, Robert R.

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AU - Fontán, Gumersindo

AU - Lee, Annette T.

AU - Ortmann, Ward

AU - Urcelay, Elena

AU - Fernández-Arquero, Miguel

AU - Núnez, Concepción

AU - Jorgensen, Gudmundur

AU - Ludviksson, Björn R.

AU - Koskinen, Sinikka

AU - Haimila, Katri

AU - Clark, Hilary F.

AU - Klareskog, Lars

AU - Gregersen, Peter K.

AU - Behrens, Timothy W.

AU - HammarströM, Lennart

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Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency

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