- Title
- Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects
- Creator
- Lill, Christina M.; Liu, Tian; Blaschke, Paul; Winkelmann, Alexander; Gerdes, Lisa-Ann; Luessi, Felix; Fernadez, Oscar; Izquierdo, Guillermo; Antiguedad, Alfredo; Hoffjan, Sabine; Cournu-Rebeix, Isabelle; Gromoller, Silvana; Schjeide, Brit-Maren M.; Faber, Hans; Liebsch, Maria; Meissner, Esther; Chanvillard, Coralie; Touze, Emmauel; Pico, Fernando; Corcia, Philippe; Bahlo, Melanie; Booth, David R.; Broadley, Simon; Roehr, Johannes T.; Brown, Matthew A.; Browning, Brian L.; Browning, Sharon R.; Butzkueven, Helmut; Carroll, William M.; Cox, Mathew B.; Chapman, Caron; Clarke, Glynnis; Danoy, Patrick; Drysdale, Karen; Akkad, Denis A.; Field, Judith; Foote, Simon J.; Greer, Judith M.; Griffiths, Lyn R.; Hadler, Johanna; Jensen, Cathy J.; Johnson, Laura J.; Kermode, Allan G.; Heard, Robert N.; Kilpatrick, Trevor J.; Damotte, Vincent; Lechner-Scott, Jeanette; Marriott, Mark; Mason, Deborah; Moscato, Pablo; Pender, Michael P.; Perreau, Victoria M.; Rubio, Justin P.; Scott, Rodney J.; Slee, Mark; Stankovich, Jim; Alcina, Antonio; Stewart, Graeme J.; Tajouri, Lofti; Taylor, Bruce V.; Wiley, James; Wilkins, Ella J.; Dörner, Thomas; Steinhagen-Thiessen, Elisabeth; Baeckman, Lars; Heekeren, Hauke R.; Li, Shu-Chen; Ortiz, Miguel A.; Lindenberger, Ulman; Chan, Andrew; Hartung, Hans-Peter; Aktas, Orhan; Lohse, Peter; Kümpfel, Tania; Kubisch, Christian; Epplen, Joerg T.; Zettl, Uwe K.; Fontaine, Bertrand; Arroyo, Rafa; Vandenbroeck, Koen; Matesanz, Fuencisla; Urcelay, Elena; Bertram, Lars; Zipp, Frauke; Lopez de Lapuente, Aitzkoa
- Relation
- Journal of Medical Genetics Vol. 49, Issue 9, p. 558-562
- Publisher Link
- http://dx.doi.org/10.1136/jmedgenet-2012-101175
- Publisher
- BMJ Group
- Resource Type
- journal article
- Date
- 2012
- Description
- 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.
- Subject
- multiple sclerosis; single nucleotide polymorphisms; genome-wide association studies
- Identifier
- http://hdl.handle.net/1959.13/1326050
- Identifier
- uon:25354
- Identifier
- ISSN:0022-2593
- Language
- eng
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