title: ANKRD55 and DHCR7 are novel multiple sclerosis risk loci.
abstract: 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.
authors: Neurogenomiks Laboratory, Department of Neuroscience, University of the Basque Country UPV/EHU, Leioa, Spain.
authors: I
authors: I
authors: Alloza
authors: D
authors: D
authors: Otaegui
authors: A Lopez
authors: AL
authors: de Lapuente
authors: A
authors: A
authors: Antigüedad
authors: J
authors: J
authors: Varadé
authors: C
authors: C
authors: Núñez
authors: R
authors: R
authors: Arroyo
authors: E
authors: E
authors: Urcelay
authors: O
authors: O
authors: Fernandez
authors: L
authors: L
authors: Leyva
authors: M
authors: M
authors: Fedetz
authors: G
authors: G
authors: Izquierdo
authors: M
authors: M
authors: Lucas
authors: B
authors: B
authors: Oliver-Martos
authors: A
authors: A
authors: Alcina
authors: A
authors: A
authors: Saiz
authors: Y
authors: Y
authors: Blanco
authors: M
authors: M
authors: Comabella
authors: X
authors: X
authors: Montalban
authors: J
authors: J
authors: Olascoaga
authors: F
authors: F
authors: Matesanz
authors: K
authors: K
authors: Vandenbroeck
mesh_terms: D000328:Adult; D000483:Alleles; D017089:Ankyrin Repeat / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase