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

被引：26

作者：

Lill, Christina M. ^{[1
,29
]}

Liu, Tian ^{[1
,2
]}

Schjeide, Brit-Maren M. ^{[1
]}

Roehr, Johannes T. ^{[1
]}

Akkad, Denis A. ^{[3
]}

Damotte, Vincent ^{[4
]}

Alcina, Antonio ^{[5
]}

Ortiz, Miguel A. ^{[6
]}

Arroyo, Rafa ^{[7
]}

Lopez de lapuente, Aitzkoa ^{[8
]}

Blaschke, Paul ^{[9
]}

Winkelmann, Alexander ^{[9
]}

Gerdes, Lisa-Ann ^{[10
]}

Luessi, Felix ^{[29
]}

Fernadez, Oscar ^{[11
]}

Izquierdo, Guillermo ^{[11
]}

Antigueedad, Alfredo ^{[12
]}

Hoffjan, Sabine ^{[3
]}

Cournu-Rebeix, Isabelle ^{[4
,13
]}

Gromoeller, Silvana ^{[1
]}

Faber, Hans ^{[14
]}

Liebsch, Maria ^{[1
]}

Meissner, Esther ^{[1
]}

Chanvillard, Coralie ^{[15
,16
]}

Touze, Emmanuel ^{[17
]}

Pico, Fernando ^{[18
]}

Corcia, Philippe ^{[19
]}

Doerner, Thomas ^{[20
]}

Steinhagen-Thiessen, Elisabeth ^{[21
]}

Baeckman, Lars ^{[22
]}

Heekeren, Hauke R. ^{[2
,23
]}

Li, Shu-Chen ^{[2
]}

Lindenberger, Ulman ^{[2
]}

Chan, Andrew ^{[24
]}

Hartung, Hans-Peter ^{[25
]}

Aktas, Orhan ^{[25
]}

Lohse, Peter ^{[26
]}

Kuempfel, Tania ^{[10
]}

Kubisch, Christian ^{[27
]}

Epplen, Joerg T. ^{[3
]}

Zettl, Uwe K. ^{[9
]}

Fontaine, Bertrand ^{[4
,11
]}

Vandenbroeck, Koen ^{[8
,28
]}

Matesanz, Fuencisla ^{[5
]}

Urcelay, Elena ^{[7
]}

Bertram, Lars ^{[1
]}

Zipp, Frauke ^{[29
]}

机构：

[1] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany

[2] Max Planck Inst Human Dev, Berlin, Germany

[3] Ruhr Univ Bochum, Dept Human Genet, Bochum, Germany

[4] Hop La Pitie Salpetriere, INSERM CNRS UPMC ICM, UMR 975 7225, Inst Cerveau Moelle, Paris, France

[5] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain

[6] Hosp Clin San Carlos, Inst Invest Sanitaria San Carlos IdISSC, Dept Immunol, Madrid, Spain

[7] Hosp Clin San Carlos, Inst Invest Sanitaria San Carlos IdISSC, Dept Neurol, Multiple Sclerosis Unit, Madrid, Spain

[8] Univ Basque Country, UPV EHU, Dept Neurosci, Neurogen Lab, Leioa, Spain

[9] Univ Rostock, Dept Neurol, Rostock, Germany

[10] Univ Munich, Inst Clin Neuroimmunol, Munich, Germany

[11] Hosp Virgen Macarena, Unidad Esclerosis Multiple, Seville, Spain

[12] Hosp Basurto, Serv Neurol, Bilbao, Spain

[13] Hop La Pitie Salpetriere, Dept Neurol, Paris, France

[14] Max Planck Inst Psychiat, Neurol Sect, D-8000 Munich, Germany

[15] Expt & Clin Res Ctr, Berlin, Germany

[16] Max Delbruck Ctr Mol Med, Berlin, Germany

[17] Hop St Anne, Dept Neurol, F-75674 Paris, France

[18] Ctr Hosp Versailles, Dept Neurol, Le Chesnay, France

[19] CHR Univ, Dept Neurol, Tours, France

[20] Charite, Dept Med Rheumatol & Clin Immunol, D-13353 Berlin, Germany

[21] Charite, Lipids Clin, Interdisciplinary Metab Ctr, D-13353 Berlin, Germany

[22] Karolinska Inst, Aging Res Ctr, Stockholm, Sweden

[23] Free Univ Berlin, Dept Educ & Psychol, Berlin, Germany

[24] Ruhr Univ Bochum, Dept Neurol, Bochum, Germany

[25] Univ Dusseldorf, Fac Med, Dept Neurol, D-40225 Dusseldorf, Germany

[26] Univ Munich, Dept Clin Chem, Munich, Germany

[27] Univ Ulm, Inst Human Genet, Ulm, Germany

[28] Basque Fdn Sci, IKERBASQUE, Bilbao, Spain

[29] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Neurol, D-55131 Mainz, Germany

来源：

JOURNAL OF MEDICAL GENETICS | 2012年 / 49卷 / 09期

基金：

瑞典研究理事会;

关键词：

SUSCEPTIBILITY LOCI; METAANALYSIS; SEVERITY;

D O I：

10.1136/jmedgenet-2012-101175

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background Single nucleotide polymorphisms (SNPs) rs429358 (epsilon 4) and rs7412 (epsilon 2), 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.

引用

页码：558 / 562

页数：5

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