ANKRD55 and DHCR7 are novel multiple sclerosis risk loci

被引：35

作者：

Alloza, I. ^{[1
]}

Otaegui, D. ^{[2
]}

Lopez de Lapuente, A. ^{[1
]}

Antigueedad, A. ^{[3
]}

Varade, J. ^{[4
]}

Nunez, C. ^{[4
]}

Arroyo, R. ^{[5
]}

Urcelay, E. ^{[4
]}

Fernandez, O. ^{[6
,7
]}

Leyva, L. ^{[6
,7
]}

Fedetz, M. ^{[8
]}

Izquierdo, G. ^{[9
]}

Lucas, M. ^{[10
]}

Oliver-Martos, B. ^{[6
,7
]}

Alcina, A. ^{[8
]}

Saiz, A. ^{[11
]}

Blanco, Y. ^{[11
]}

Comabella, M. ^{[12
]}

Montalban, X. ^{[12
]}

Olascoaga, J. ^{[13
]}

Matesanz, F. ^{[8
,9
]}

Vandenbroeck, K. ^{[1
,14
]}

机构：

[1] Univ Basque Country UPV EHU, Dept Neurosci, Neurogenomiks Lab, Leioa, Spain

[2] Inst Invest Sanitaria Biodonostia, Area Neurociencias, San Sebastian, Spain

[3] Hosp Basurto, Serv Neurol, Bilbao, Spain

[4] Inst Invest Sanitaria San Carlos, Hosp Clin San Carlos, Dept Immunol, Madrid, Spain

[5] Inst Invest Sanitaria San Carlos, Neurol Dept H Clin S Carlos, Multiple Sclerosis Unit, Madrid, Spain

[6] Hosp Reg Univ Carlos Haya Malaga, Inst Neurociencias Clin, Serv Neurol, Malaga, Spain

[7] Hosp Reg Univ Carlos Haya Malaga, Inst Neurociencias Clin, Lab Invest, Malaga, Spain

[8] CSIC, Inst Parasitol & Biomed LopezNeyra, Granada, Spain

[9] Hosp Virgen Macarena, Unidad Esclerosis Multiple, Seville, Spain

[10] Hosp Virgen Macarena, Serv Biol Mol, Seville, Spain

[11] Hosp Clin & Inst Invest Biomed Pi & Sunyer, Neurol Serv, Barcelona, Spain

[12] Hosp Univ Vall dHebron, Unitat Neuroimmunol Clin, CEM Cat, Ctr Esclerosi Multiple Catalunya, Barcelona, Spain

[13] Hosp Donostia, Unidad Esclerosis Multiple, Serv Neurol, San Sebastian, Spain

[14] Basque Fdn Sci, IKERBASQUE, Bilbao, Spain

来源：

GENES AND IMMUNITY | 2012年 / 13卷 / 03期

关键词：

multiple sclerosis; polymorphism; susceptibility; ANKRD55; DHCR7; vitamin D; GENOME-WIDE ASSOCIATION; VITAMIN-D; SUSCEPTIBILITY LOCI; VARIANTS; DISEASE; GENE; POLYMORPHISMS; REPLICATION; IDENTIFICATION; PATHWAY;

D O I：

10.1038/gene.2011.81

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Multiple sclerosis (MS) shares some risk genes with other disorders hallmarked by an autoimmune pathogenesis, most notably IL2RA and CLEC16A. We analyzed 10 single-nucleotide polymorphisms (SNPs) in nine risk genes, which recently emerged from a series of non-MS genome-wide association studies (GWAS), in a Spanish cohort comprising 2895 MS patients and 2942 controls. We identified two SNPs associated with MS. The first SNP, rs6859219, located in ANKRD55 (Chr5), was recently discovered in a meta-analysis of GWAS on rheumatoid arthritis (RA), and emerged from this study with genome-wide significance (odds ratio (OR) = 1.35; P = 2.3 x 10(-9)). The second SNP, rs12785878, is located near DHCR7 (Chr11), a genetic determinant of vitamin D insufficiency, and showed a size effect in MS similar to that recently observed in Type 1 diabetes (T1D; OR = 1.10; P=0.009). ANKRD55 is a gene of unknown function, and is flanked proximally by the IL6ST-IL31RA gene cluster. However, rs6859219 did not show correlation with a series of haplotype-tagging SNPs covering IL6ST-IL31RA, analyzed in a subset of our dataset (D' < 0.31; r(2) < 0.011). Our results expand the number of risk genes shared between MS, RA and T1D.

引用

页码：253 / 257

页数：5

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