Anatomy and Neuroscience - Research Publications
Permanent URI for this collection
Now showing 1 - 2 of 2
ItemClosing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjectsLill, CM ; Liu, T ; Schjeide, B-MM ; Roehr, JT ; Akkad, DA ; Damotte, V ; Alcina, A ; Ortiz, MA ; Arroyo, R ; Lopez de lapuente, A ; Blaschke, P ; Winkelmann, A ; Gerdes, L-A ; Luessi, F ; Fernadez, O ; Izquierdo, G ; Antigueedad, A ; Hoffjan, S ; Cournu-Rebeix, I ; Gromoeller, S ; Faber, H ; Liebsch, M ; Meissner, E ; Chanvillard, C ; Touze, E ; Pico, F ; Corcia, P ; Doerner, T ; Steinhagen-Thiessen, E ; Baeckman, L ; Heekeren, HR ; Li, S-C ; Lindenberger, U ; Chan, A ; Hartung, H-P ; Aktas, O ; Lohse, P ; Kuempfel, T ; Kubisch, C ; Epplen, JT ; Zettl, UK ; Fontaine, B ; Vandenbroeck, K ; Matesanz, F ; Urcelay, E ; Bertram, L ; Zipp, F (BMJ PUBLISHING GROUP, 2012-09-01)BACKGROUND: Single nucleotide polymorphisms (SNPs) rs429358 (ε4) and rs7412 (ε2), both invoking changes in the amino-acid sequence of the apolipoprotein E (APOE) gene, have previously been tested for association with multiple sclerosis (MS) risk. However, none of these studies was sufficiently powered to detect modest effect sizes at acceptable type-I error rates. As both SNPs are only imperfectly captured on commonly used microarray genotyping platforms, their evaluation in the context of genome-wide association studies has been hindered until recently. METHODS: We genotyped 12 740 subjects hitherto not studied for their APOE status, imputed raw genotype data from 8739 subjects from five independent genome-wide association studies datasets using the most recent high-resolution reference panels, and extracted genotype data for 8265 subjects from previous candidate gene assessments. RESULTS: Despite sufficient power to detect associations at genome-wide significance thresholds across a range of ORs, our analyses did not support a role of rs429358 or rs7412 on MS susceptibility. This included meta-analyses of the combined data across 13 913 MS cases and 15 831 controls (OR=0.95, p=0.259, and OR 1.07, p=0.0569, for rs429358 and rs7412, respectively). CONCLUSION: Given the large sample size of our analyses, it is unlikely that the two APOE missense SNPs studied here exert any relevant effects on MS susceptibility.
ItemIdentity-by-Descent Mapping to Detect Rare Variants Conferring Susceptibility to Multiple SclerosisLin, Rui ; Charlesworth, Jac ; Stankovich, Jim ; PERREAU, VICTORIA ; Brown, Matthew ; TAYLOR, BRUCE ( 2012)