TY - JOUR T1 - Closing the case of <em>APOE</em> in multiple sclerosis: no association with disease risk in over 29 000 subjects JF - Journal of Medical Genetics JO - J Med Genet SP - 558 LP - 562 DO - 10.1136/jmedgenet-2012-101175 VL - 49 IS - 9 AU - Christina M Lill AU - Tian Liu AU - Brit-Maren M Schjeide AU - Johannes T Roehr AU - Denis A Akkad AU - Vincent Damotte AU - Antonio Alcina AU - Miguel A Ortiz AU - Rafa Arroyo AU - Aitzkoa Lopez de Lapuente AU - Paul Blaschke AU - Alexander Winkelmann AU - Lisa-Ann Gerdes AU - Felix Luessi AU - Oscar Fernadez AU - Guillermo Izquierdo AU - Alfredo Antigüedad AU - Sabine Hoffjan AU - Isabelle Cournu-Rebeix AU - Silvana Gromöller AU - Hans Faber AU - Maria Liebsch AU - Esther Meissner AU - Coralie Chanvillard AU - Emmanuel Touze AU - Fernando Pico AU - Philippe Corcia AU - Thomas Dörner AU - Elisabeth Steinhagen-Thiessen AU - Lars Baeckman AU - Hauke R Heekeren AU - Shu-Chen Li AU - Ulman Lindenberger AU - Andrew Chan AU - Hans-Peter Hartung AU - Orhan Aktas AU - Peter Lohse AU - Tania Kümpfel AU - Christian Kubisch AU - Joerg T Epplen AU - Uwe K Zettl AU - Bertrand Fontaine AU - Koen Vandenbroeck AU - Fuencisla Matesanz AU - Elena Urcelay AU - Lars Bertram AU - Frauke Zipp Y1 - 2012/09/01 UR - http://jmg.bmj.com/content/49/9/558.abstract N2 - 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. ER -