Clear Search sequence regions


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.

Citation

I Alloza, D Otaegui, A Lopez de Lapuente, A Antigüedad, J Varadé, C Núñez, R Arroyo, E Urcelay, O Fernandez, L Leyva, M Fedetz, G Izquierdo, M Lucas, B Oliver-Martos, A Alcina, A Saiz, Y Blanco, M Comabella, X Montalban, J Olascoaga, F Matesanz, K Vandenbroeck. ANKRD55 and DHCR7 are novel multiple sclerosis risk loci. Genes and immunity. 2012 Apr;13(3):253-7

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PMID: 22130326

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