TY - JOUR
T1 - ANKRD55 and DHCR7 are novel multiple sclerosis risk loci
AU - Montalban, Xavier
AU - Alloza, I.
AU - Otaegui, D.
AU - De Lapuente, A. Lopez
AU - Antigüedad, A.
AU - Varadé, J.
AU - Nú̃ez, C.
AU - Arroyo, R.
AU - Urcelay, E.
AU - Fernandez, O.
AU - Leyva, L.
AU - Fedetz, M.
AU - Izquierdo, G.
AU - Lucas, M.
AU - Oliver-Martos, B.
AU - Alcina, A.
AU - Saiz, A.
AU - Blanco, Y.
AU - Comabella, M.
AU - Olascoaga, J.
AU - Matesanz, F.
AU - Vandenbroeck, K.
N1 - Financial support for the study was provided by: the Gobierno Vasco (reference IT512-10; Convocatoria ‘Grupos de Investigación 2010–2015’), the Ministerio de Ciencia e Innovación-FondosFeder (SAF2009-11491), the Fondo de Investigación Sanitaria FIS (RETICS-REEM RD07/0060, PI081636, PI10/1985, PS09/02105), the Junta de Andalucía (P07-CVI-02551), Ikerbasque, the Basque Foundation for Science (Bilbao) and FundaciónIlundain. SNP genotyping services were provided by the Spanish ‘Centro Nacional de Genotipado CEGEN-USC, http://www.cegen.org’.
PY - 2012/4
Y1 - 2012/4
N2 - 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 × 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.
AB - 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 × 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.
KW - ANKRD55
KW - DHCR7
KW - multiple sclerosis
KW - Polymorphism
KW - Susceptibility
KW - Vitamin D
UR - http://www.scopus.com/inward/record.url?scp=84859926176&partnerID=8YFLogxK
U2 - 10.1038/gene.2011.81
DO - 10.1038/gene.2011.81
M3 - Article
C2 - 22130326
AN - SCOPUS:84859926176
SN - 1466-4879
VL - 13
SP - 253
EP - 257
JO - Genes and Immunity
JF - Genes and Immunity
IS - 3
ER -
