Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis

被引：55

作者：

Hoppenbrouwers, Ilse A. ^{[1
]}

Aulchenko, Yurii S. ^{[2
,3
]}

Janssens, A. Cecile ^{[4
]}

Ramagopalan, Sreeram V. ^{[5
,6
]}

Broer, Linda ^{[1
,2
,3
]}

Kayser, Manfred ^{[7
]}

Ebers, George C. ^{[5
,6
]}

Oostra, Ben A. ^{[2
,3
]}

van Duijn, Cornelia M. ^{[2
,3
]}

Hintzen, Rogier Q. ^{[1
]}

机构：

[1] Erasmus MC, Dept Neurol, MS Ctr ErasMS, NL-3000 CA Rotterdam, Netherlands

[2] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3000 CA Rotterdam, Netherlands

[3] Erasmus MC, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands

[4] Erasmus MC, Dept Publ Hlth, NL-3000 CA Rotterdam, Netherlands

[5] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[6] Univ Oxford, Dept Clin Neurol, Oxford, England

[7] Erasmus MC, Dept Forens Mol Biol, NL-3000 CA Rotterdam, Netherlands

来源：

JOURNAL OF HUMAN GENETICS | 2009年 / 54卷 / 11期

关键词：

CD58; CLEC16A; meta-analysis; multiple sclerosis; replication; risk genes; INTERLEUKIN-7; RECEPTOR; SUSCEPTIBILITY LOCI; AUTOIMMUNE-DISEASES; ASSOCIATION;

D O I：

10.1038/jhg.2009.96

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

A recent genome-wide association study by the International Multiple Sclerosis Genetics Consortium (IMSGC) reported association of 17 single-nucleotide polymorphisms (SNPs) in 14 loci with multiple sclerosis (MS). Only two loci, HLA-DRA and IL2RA, reached genome-wide significance (P < 5E-08). In our study, we determined whether we could replicate the results of the IMSGC and whether more SNPs are genome-wide significantly associated with MS. We assessed the association between the 17 IMSGC SNPs and MS in three cohorts (total number of subjects 3981, among these 1853 cases). We performed a meta-analysis of the results of our study, the original IMSGC results and the results of a recent replication study performed in the Australian population. Of the 17 IMSGC SNPs, five SNPs showed genome-wide significant association with MS: HLA-DRA (P=8E-124), IL7R (P=6E-09), IL2RA (P=1E-11), CD58 (P=4E-09) and CLEC16A (P=3E-12). Therefore, genome-wide significance has now been shown for SNPs in different non-HLA MS risk genes. Several of these risk genes, including CD58 and CLEC16A, are shared by different autoimmune diseases. Fine mapping studies will be needed to determine the functional contributions to distinct autoimmune phenotypes. Journal of Human Genetics (2009) 54, 676-680; doi:10.1038/jhg.2009.96; published online 16 October 2009

引用

页码：676 / 680

页数：5

共 27 条

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