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A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE

Sandling, Johanna K.; Garnier, Sophie; Sigurdsson, Snaevar; Wang, Chuan; Nordmark, Gunnel; Gunnarsson, Iva; Svenungsson, Elisabet; Padyukov, Leonid; Sturfelt, Gunnar LU and Jönsen, Andreas LU , et al. (2011) In European Journal of Human Genetics 19(4). p.479-484
Abstract
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P < 0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this... (More)
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P < 0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort. To replicate these findings we extracted data from a genomewide association study on SLE performed in a US cohort. Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (P-meta=0.00010 and P-meta=0.00040, respectively). STAT1 was also associated with SLE in this cohort (P-meta=3.3 x 10(-5)), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene. Our study suggests additional genes from the type I interferon system in SLE, and highlights genes in this pathway for further functional analysis. European Journal of Human Genetics (2011) 19, 479-484; doi:10.1038/ejhg.2010.197; published online 22 December 2010 (Less)
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published
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keywords
systemic lupus erythematosus, type I interferon system, candidate gene, study, single nucleotide polymorphism, IKBKE, IL8
in
European Journal of Human Genetics
volume
19
issue
4
pages
479 - 484
publisher
Nature Publishing Group
external identifiers
  • wos:000288505000020
  • scopus:79952773104
ISSN
1476-5438
DOI
10.1038/ejhg.2010.197
language
English
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yes
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05d60f97-a715-4a3f-99ef-fbed014dbcfc (old id 1936264)
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2011-05-02 07:52:48
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2017-10-01 03:14:38
@article{05d60f97-a715-4a3f-99ef-fbed014dbcfc,
  abstract     = {Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P &lt; 0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort. To replicate these findings we extracted data from a genomewide association study on SLE performed in a US cohort. Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (P-meta=0.00010 and P-meta=0.00040, respectively). STAT1 was also associated with SLE in this cohort (P-meta=3.3 x 10(-5)), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene. Our study suggests additional genes from the type I interferon system in SLE, and highlights genes in this pathway for further functional analysis. European Journal of Human Genetics (2011) 19, 479-484; doi:10.1038/ejhg.2010.197; published online 22 December 2010},
  author       = {Sandling, Johanna K. and Garnier, Sophie and Sigurdsson, Snaevar and Wang, Chuan and Nordmark, Gunnel and Gunnarsson, Iva and Svenungsson, Elisabet and Padyukov, Leonid and Sturfelt, Gunnar and Jönsen, Andreas and Bengtsson, Anders and Truedsson, Lennart and Eriksson, Catharina and Rantapaa-Dahlqvist, Solbritt and Malarstig, Anders and Strawbridge, Rona J. and Hamsten, Anders and Criswell, Lindsey A. and Graham, Robert R. and Behrens, Timothy W. and Eloranta, Maija-Leena and Alm, Gunnar and Ronnblom, Lars and Syvanen, Ann-Christine},
  issn         = {1476-5438},
  keyword      = {systemic lupus erythematosus,type I interferon system,candidate gene,study,single nucleotide polymorphism,IKBKE,IL8},
  language     = {eng},
  number       = {4},
  pages        = {479--484},
  publisher    = {Nature Publishing Group},
  series       = {European Journal of Human Genetics},
  title        = {A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE},
  url          = {http://dx.doi.org/10.1038/ejhg.2010.197},
  volume       = {19},
  year         = {2011},
}