Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Eur J Hum Genet. 2013 Sep;21(9):994-9. doi: 10.1038/ejhg.2012.277. Epub 2012 Dec 19.
Recent genome-wide association studies (GWASs) conducted in Asian populations have identified novel risk loci for systemic lupus erythematosus (SLE). Here, we genotyped 10 single-nucleotide polymorphisms (SNPs) in eight such loci and investigated their disease associations in three independent Caucasian SLE case-control cohorts recruited from Sweden, Finland and the United States. The disease associations of the SNPs in ETS1, IKZF1, LRRC18-WDFY4, RASGRP3, SLC15A4, TNIP1 and 16p11.2 were replicated, whereas no solid evidence of association was observed for the 7q11.23 locus in the Caucasian cohorts. SLC15A4 was significantly associated with renal involvement in SLE. The association of TNIP1 was more pronounced in SLE patients with renal and immunological disorder, which is corroborated by two previous studies in Asian cohorts. The effects of all the associated SNPs, either conferring risk for or being protective against SLE, were in the same direction in Caucasians and Asians. The magnitudes of the allelic effects for most of the SNPs were also comparable across different ethnic groups. On the contrary, remarkable differences in allele frequencies between Caucasian and Asian populations were observed for all associated SNPs. In conclusion, most of the novel SLE risk loci identified by GWASs in Asian populations were also associated with SLE in Caucasian populations. We observed both similarities and differences with respect to the effect sizes and risk allele frequencies across ethnicities.
最近在亚洲人群中进行的全基因组关联研究(GWAS)确定了系统性红斑狼疮(SLE)的新风险位点。在这里,我们对八个这样的位点中的 10 个单核苷酸多态性(SNP)进行了基因分型,并在来自瑞典、芬兰和美国的三个独立的白种人 SLE 病例对照队列中研究了它们的疾病相关性。ETS1、IKZF1、LRRC18-WDFY4、RASGRP3、SLC15A4、TNIP1 和 16p11.2 中的 SNP 的疾病相关性得到了复制,而在白种人队列中,7q11.23 位点没有明显的关联证据。SLC15A4 与 SLE 中的肾脏受累显著相关。TNIP1 与 SLE 患者的肾脏和免疫紊乱的相关性更为显著,这与亚洲队列的两项先前研究相吻合。所有相关 SNP 赋予 SLE 风险或保护 SLE 的作用方向在白种人和亚洲人是一致的。大多数 SNP 的等位基因效应大小在不同的种族群体中也是可比的。相反,所有相关 SNP 的等位基因频率在白种人和亚洲人群体之间存在显著差异。总之,GWAS 在亚洲人群中确定的大多数新的 SLE 风险位点也与白种人群中的 SLE 相关。我们观察到了在效应大小和风险等位基因频率方面的相似性和差异性。
Eur J Hum Genet. 2012-12-19
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