APOE epsilon variation in multiple sclerosis susceptibility and disease severity: Some answers

R. M. Burwick, P. P. Ramsay, J. L. Haines, S. L. Hauser, J. R. Oksenberg, Margaret A Pericak-Vance, S. Schmidt, A. Compston, S. Sawcer, R. Cittadella, G. Savettieri, A. Quattrone, C. H. Polman, B. M J Uitdehaag, J. N P Zwemmer, C. P. Hawkins, W. E R Ollier, S. Weatherby, C. Enzinger, F. FazekasH. Schmidt, R. Schmidt, J. Hillert, T. Masterman, P. Hogh, M. Niino, S. Kikuchi, P. Maciel, M. Santos, M. E. Rio, H. Kwiecinski, B. Zakrzewska-Pniewska, N. Evangelou, J. Palace, L. F. Barcellos

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Abstract

Background: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. Methods: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. Results: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of ε2 or ε4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96-1.34 and OR 0.89, 95% CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. Conclusion: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.

Original languageEnglish
Pages (from-to)1373-1383
Number of pages11
JournalNeurology
Volume66
Issue number9
DOIs
StatePublished - May 1 2006
Externally publishedYes

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Disease Susceptibility
Multiple Sclerosis
Genotype
Meta-Analysis
PubMed
Sample Size
Phenotype

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Burwick, R. M., Ramsay, P. P., Haines, J. L., Hauser, S. L., Oksenberg, J. R., Pericak-Vance, M. A., ... Barcellos, L. F. (2006). APOE epsilon variation in multiple sclerosis susceptibility and disease severity: Some answers. Neurology, 66(9), 1373-1383. https://doi.org/10.1212/01.wnl.0000210531.19498.3f

APOE epsilon variation in multiple sclerosis susceptibility and disease severity : Some answers. / Burwick, R. M.; Ramsay, P. P.; Haines, J. L.; Hauser, S. L.; Oksenberg, J. R.; Pericak-Vance, Margaret A; Schmidt, S.; Compston, A.; Sawcer, S.; Cittadella, R.; Savettieri, G.; Quattrone, A.; Polman, C. H.; Uitdehaag, B. M J; Zwemmer, J. N P; Hawkins, C. P.; Ollier, W. E R; Weatherby, S.; Enzinger, C.; Fazekas, F.; Schmidt, H.; Schmidt, R.; Hillert, J.; Masterman, T.; Hogh, P.; Niino, M.; Kikuchi, S.; Maciel, P.; Santos, M.; Rio, M. E.; Kwiecinski, H.; Zakrzewska-Pniewska, B.; Evangelou, N.; Palace, J.; Barcellos, L. F.

In: Neurology, Vol. 66, No. 9, 01.05.2006, p. 1373-1383.

Research output: Contribution to journalArticle

Burwick, RM, Ramsay, PP, Haines, JL, Hauser, SL, Oksenberg, JR, Pericak-Vance, MA, Schmidt, S, Compston, A, Sawcer, S, Cittadella, R, Savettieri, G, Quattrone, A, Polman, CH, Uitdehaag, BMJ, Zwemmer, JNP, Hawkins, CP, Ollier, WER, Weatherby, S, Enzinger, C, Fazekas, F, Schmidt, H, Schmidt, R, Hillert, J, Masterman, T, Hogh, P, Niino, M, Kikuchi, S, Maciel, P, Santos, M, Rio, ME, Kwiecinski, H, Zakrzewska-Pniewska, B, Evangelou, N, Palace, J & Barcellos, LF 2006, 'APOE epsilon variation in multiple sclerosis susceptibility and disease severity: Some answers', Neurology, vol. 66, no. 9, pp. 1373-1383. https://doi.org/10.1212/01.wnl.0000210531.19498.3f
Burwick, R. M. ; Ramsay, P. P. ; Haines, J. L. ; Hauser, S. L. ; Oksenberg, J. R. ; Pericak-Vance, Margaret A ; Schmidt, S. ; Compston, A. ; Sawcer, S. ; Cittadella, R. ; Savettieri, G. ; Quattrone, A. ; Polman, C. H. ; Uitdehaag, B. M J ; Zwemmer, J. N P ; Hawkins, C. P. ; Ollier, W. E R ; Weatherby, S. ; Enzinger, C. ; Fazekas, F. ; Schmidt, H. ; Schmidt, R. ; Hillert, J. ; Masterman, T. ; Hogh, P. ; Niino, M. ; Kikuchi, S. ; Maciel, P. ; Santos, M. ; Rio, M. E. ; Kwiecinski, H. ; Zakrzewska-Pniewska, B. ; Evangelou, N. ; Palace, J. ; Barcellos, L. F. / APOE epsilon variation in multiple sclerosis susceptibility and disease severity : Some answers. In: Neurology. 2006 ; Vol. 66, No. 9. pp. 1373-1383.
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abstract = "Background: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. Methods: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. Results: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of ε2 or ε4 status on MS risk was observed (summary OR 1.14, 95{\%} CI 0.96-1.34 and OR 0.89, 95{\%} CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. Conclusion: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.",
author = "Burwick, {R. M.} and Ramsay, {P. P.} and Haines, {J. L.} and Hauser, {S. L.} and Oksenberg, {J. R.} and Pericak-Vance, {Margaret A} and S. Schmidt and A. Compston and S. Sawcer and R. Cittadella and G. Savettieri and A. Quattrone and Polman, {C. H.} and Uitdehaag, {B. M J} and Zwemmer, {J. N P} and Hawkins, {C. P.} and Ollier, {W. E R} and S. Weatherby and C. Enzinger and F. Fazekas and H. Schmidt and R. Schmidt and J. Hillert and T. Masterman and P. Hogh and M. Niino and S. Kikuchi and P. Maciel and M. Santos and Rio, {M. E.} and H. Kwiecinski and B. Zakrzewska-Pniewska and N. Evangelou and J. Palace and Barcellos, {L. F.}",
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T1 - APOE epsilon variation in multiple sclerosis susceptibility and disease severity

T2 - Some answers

AU - Burwick, R. M.

AU - Ramsay, P. P.

AU - Haines, J. L.

AU - Hauser, S. L.

AU - Oksenberg, J. R.

AU - Pericak-Vance, Margaret A

AU - Schmidt, S.

AU - Compston, A.

AU - Sawcer, S.

AU - Cittadella, R.

AU - Savettieri, G.

AU - Quattrone, A.

AU - Polman, C. H.

AU - Uitdehaag, B. M J

AU - Zwemmer, J. N P

AU - Hawkins, C. P.

AU - Ollier, W. E R

AU - Weatherby, S.

AU - Enzinger, C.

AU - Fazekas, F.

AU - Schmidt, H.

AU - Schmidt, R.

AU - Hillert, J.

AU - Masterman, T.

AU - Hogh, P.

AU - Niino, M.

AU - Kikuchi, S.

AU - Maciel, P.

AU - Santos, M.

AU - Rio, M. E.

AU - Kwiecinski, H.

AU - Zakrzewska-Pniewska, B.

AU - Evangelou, N.

AU - Palace, J.

AU - Barcellos, L. F.

PY - 2006/5/1

Y1 - 2006/5/1

N2 - Background: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. Methods: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. Results: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of ε2 or ε4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96-1.34 and OR 0.89, 95% CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. Conclusion: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.

AB - Background: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. Methods: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. Results: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of ε2 or ε4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96-1.34 and OR 0.89, 95% CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. Conclusion: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.

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