Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects

Lill, Christina M., Liu, Tian, Schjeide, Brit-Marem, Roehr, Johannes T., Akkad, Denis A., Damotte, Vincent, Alcina, Antonio, Ortiz, Migual A., Arroyo, Rafa, Lopez de Lapuente, Aitzkoa, Blaschke, Paul, Winkelmann, Alexander, Gerdes, Lisa-Ann, Luessi, Felix, Fernadez, Oscar, Izquierdo, Guillermo, Antiguedad, Alfredo, Hoffjan, Sabine, Cournu-Reibeix, Isabelle, Gromoller, Silvana, Faber, Hans, Liebsch, Maria, Meissner, Esther, Chanvillard, Coralie, Touze, Emmanuel, Pico, Fernando, Corcia, Philippe, 19ANZgene Consortium, Bahlo, Melanie, Booth, David R., Broadley, Simon A., 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, Field, Judith, Foote, Simon J., Greer, Judith M., Griffiths, Lyn R., Hadler, Johanna, Jensen, Cathy J., Johnson, Laura J., Kermode, Allan G., Heard, Rober N., Kilpatrick, Trevor J., 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, Stewart, Graeme J., Tajouri, Lotfi, Taylor, Bruce V., Wiley, James, Wilkins, Ella J., Dorner, Thomas, Steinhagen-Thiessen, Elisabeth, Baeckman, Lars, Heekeren, Hauke R., Li, Shu-Chen, Lindenberger, Ulman, Chan, Andrew, Hartung, Hans-Peter, Aktas, Orhan, Lohse, Peter, Kumpfel, Tania, Kubisch, Christian, Epplen, Joerg T., Zettl, Uwe K., Fontaine, Bertrand, Vandenbroeck, Koen, Matesanz, Fuencisla, Urcelay, Elena, Bertram, Lars and Zipp, Frauke (2012) Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects. Journal of Medical Genetics, 49 9: 558-562. doi:10.1136/jmedgenet-2012-101175

Author Lill, Christina M.
Liu, Tian
Schjeide, Brit-Marem
Roehr, Johannes T.
Akkad, Denis A.
Damotte, Vincent
Alcina, Antonio
Ortiz, Migual A.
Arroyo, Rafa
Lopez de Lapuente, Aitzkoa
Blaschke, Paul
Winkelmann, Alexander
Gerdes, Lisa-Ann
Luessi, Felix
Fernadez, Oscar
Izquierdo, Guillermo
Antiguedad, Alfredo
Hoffjan, Sabine
Cournu-Reibeix, Isabelle
Gromoller, Silvana
Faber, Hans
Liebsch, Maria
Meissner, Esther
Chanvillard, Coralie
Touze, Emmanuel
Pico, Fernando
Corcia, Philippe
19ANZgene Consortium
Bahlo, Melanie
Booth, David R.
Broadley, Simon A.
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
Field, Judith
Foote, Simon J.
Greer, Judith M.
Griffiths, Lyn R.
Hadler, Johanna
Jensen, Cathy J.
Johnson, Laura J.
Kermode, Allan G.
Heard, Rober N.
Kilpatrick, Trevor J.
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
Stewart, Graeme J.
Tajouri, Lotfi
Taylor, Bruce V.
Wiley, James
Wilkins, Ella J.
Dorner, Thomas
Steinhagen-Thiessen, Elisabeth
Baeckman, Lars
Heekeren, Hauke R.
Li, Shu-Chen
Lindenberger, Ulman
Chan, Andrew
Hartung, Hans-Peter
Aktas, Orhan
Lohse, Peter
Kumpfel, Tania
Kubisch, Christian
Epplen, Joerg T.
Zettl, Uwe K.
Fontaine, Bertrand
Vandenbroeck, Koen
Matesanz, Fuencisla
Urcelay, Elena
Bertram, Lars
Zipp, Frauke
Title Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects
Journal name Journal of Medical Genetics   Check publisher's open access policy
ISSN 0022-2593
Publication date 2012-07-23
Sub-type Article (original research)
DOI 10.1136/jmedgenet-2012-101175
Volume 49
Issue 9
Start page 558
End page 562
Total pages 5
Place of publication London, United Kingdom
Publisher B M J Group
Language eng
Formatted abstract
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.

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.

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).

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.

Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 26 Nov 2012, 23:05:47 EST by Judith M Greer on behalf of UQ Centre for Clinical Research