Genetic risk variants in African Americans with multiple sclerosis

Noriko Isobe, Pierre Antoine Gourraud, Hanne F. Harbo, Stacy J. Caillier, Adam Santaniello, Pouya Khankhanian, Martin Maiers, Stephen Spellman, Nezih Cereb, Sooyoung Yang, Marcelo J. Pando, Laura Piccio, Anne H. Cross, Philip L. De Jager, Bruce A.C. Cree, Stephen L. Hauser, Jorge R. Oksenberg

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Abstract

Objectives: To assess the association of established multiple sclerosis (MS) risk variants in 3,254 African Americans (1,162 cases and 2,092 controls). Methods: Human leukocyte antigen (HLA)-DRB1, HLA-DQB1, and HLA-A alleles were typed by molecular techniques. Single nucleotide polymorphism (SNP) genotyping was conducted for 76 MS-associated SNPs and 52 ancestry informative marker SNPs selected throughout the genome. Self-declared ancestry was refined by principal component analysis of the ancestry informative marker SNPs. An ancestry-adjusted multivariate model was applied to assess genetic associations. Results: The following major histocompatibility complex risk alleles were replicated: HLADRB1 15:01 (odds ratio [OR] 5 2.02 [95% confidence interval: 1.54-2.63], p 5 2.50e-07), HLA-DRB1 03:01 (OR 5 1.58 [1.29-1.94], p 5 1.11e-05), as well as HLA-DRB1 04:05 (OR 5 2.35 [1.26-4.37], p 5 0.007) and the African-specific risk allele of HLA-DRB1 15:03 (OR 5 1.26 [1.05-1.51], p 5 0.012). The protective association of HLA-A02:01 was confirmed (OR 5 0.72 [0.55-0.93], p 5 0.013). None of the HLA-DQB1 alleles were associated with MS. Using a significance threshold of p , 0.01, outside the major histocompatibility complex region, 8MS SNPs were also found to be associated with MS in African Americans. Conclusion: MS genetic risk in African Americans only partially overlaps with that of Europeans and could explain the difference of MS prevalence between populations.

Original languageEnglish
Pages (from-to)219-227
Number of pages9
JournalNeurology
Volume81
Issue number3
DOIs
Publication statusPublished - Jul 16 2013

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HLA Antigens
African Americans
Multiple Sclerosis
Single Nucleotide Polymorphism
Odds Ratio
Alleles
Major Histocompatibility Complex
Principal Component Analysis
varespladib methyl
Genome
Confidence Intervals
Population

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Isobe, N., Gourraud, P. A., Harbo, H. F., Caillier, S. J., Santaniello, A., Khankhanian, P., ... Oksenberg, J. R. (2013). Genetic risk variants in African Americans with multiple sclerosis. Neurology, 81(3), 219-227. https://doi.org/10.1212/WNL.0b013e31829bfe2f

Genetic risk variants in African Americans with multiple sclerosis. / Isobe, Noriko; Gourraud, Pierre Antoine; Harbo, Hanne F.; Caillier, Stacy J.; Santaniello, Adam; Khankhanian, Pouya; Maiers, Martin; Spellman, Stephen; Cereb, Nezih; Yang, Sooyoung; Pando, Marcelo J.; Piccio, Laura; Cross, Anne H.; De Jager, Philip L.; Cree, Bruce A.C.; Hauser, Stephen L.; Oksenberg, Jorge R.

In: Neurology, Vol. 81, No. 3, 16.07.2013, p. 219-227.

Research output: Contribution to journalArticle

Isobe, N, Gourraud, PA, Harbo, HF, Caillier, SJ, Santaniello, A, Khankhanian, P, Maiers, M, Spellman, S, Cereb, N, Yang, S, Pando, MJ, Piccio, L, Cross, AH, De Jager, PL, Cree, BAC, Hauser, SL & Oksenberg, JR 2013, 'Genetic risk variants in African Americans with multiple sclerosis', Neurology, vol. 81, no. 3, pp. 219-227. https://doi.org/10.1212/WNL.0b013e31829bfe2f
Isobe N, Gourraud PA, Harbo HF, Caillier SJ, Santaniello A, Khankhanian P et al. Genetic risk variants in African Americans with multiple sclerosis. Neurology. 2013 Jul 16;81(3):219-227. https://doi.org/10.1212/WNL.0b013e31829bfe2f
Isobe, Noriko ; Gourraud, Pierre Antoine ; Harbo, Hanne F. ; Caillier, Stacy J. ; Santaniello, Adam ; Khankhanian, Pouya ; Maiers, Martin ; Spellman, Stephen ; Cereb, Nezih ; Yang, Sooyoung ; Pando, Marcelo J. ; Piccio, Laura ; Cross, Anne H. ; De Jager, Philip L. ; Cree, Bruce A.C. ; Hauser, Stephen L. ; Oksenberg, Jorge R. / Genetic risk variants in African Americans with multiple sclerosis. In: Neurology. 2013 ; Vol. 81, No. 3. pp. 219-227.
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abstract = "Objectives: To assess the association of established multiple sclerosis (MS) risk variants in 3,254 African Americans (1,162 cases and 2,092 controls). Methods: Human leukocyte antigen (HLA)-DRB1, HLA-DQB1, and HLA-A alleles were typed by molecular techniques. Single nucleotide polymorphism (SNP) genotyping was conducted for 76 MS-associated SNPs and 52 ancestry informative marker SNPs selected throughout the genome. Self-declared ancestry was refined by principal component analysis of the ancestry informative marker SNPs. An ancestry-adjusted multivariate model was applied to assess genetic associations. Results: The following major histocompatibility complex risk alleles were replicated: HLADRB1 15:01 (odds ratio [OR] 5 2.02 [95{\%} confidence interval: 1.54-2.63], p 5 2.50e-07), HLA-DRB1 03:01 (OR 5 1.58 [1.29-1.94], p 5 1.11e-05), as well as HLA-DRB1 04:05 (OR 5 2.35 [1.26-4.37], p 5 0.007) and the African-specific risk allele of HLA-DRB1 15:03 (OR 5 1.26 [1.05-1.51], p 5 0.012). The protective association of HLA-A02:01 was confirmed (OR 5 0.72 [0.55-0.93], p 5 0.013). None of the HLA-DQB1 alleles were associated with MS. Using a significance threshold of p , 0.01, outside the major histocompatibility complex region, 8MS SNPs were also found to be associated with MS in African Americans. Conclusion: MS genetic risk in African Americans only partially overlaps with that of Europeans and could explain the difference of MS prevalence between populations.",
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AU - Isobe, Noriko

AU - Gourraud, Pierre Antoine

AU - Harbo, Hanne F.

AU - Caillier, Stacy J.

AU - Santaniello, Adam

AU - Khankhanian, Pouya

AU - Maiers, Martin

AU - Spellman, Stephen

AU - Cereb, Nezih

AU - Yang, Sooyoung

AU - Pando, Marcelo J.

AU - Piccio, Laura

AU - Cross, Anne H.

AU - De Jager, Philip L.

AU - Cree, Bruce A.C.

AU - Hauser, Stephen L.

AU - Oksenberg, Jorge R.

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N2 - Objectives: To assess the association of established multiple sclerosis (MS) risk variants in 3,254 African Americans (1,162 cases and 2,092 controls). Methods: Human leukocyte antigen (HLA)-DRB1, HLA-DQB1, and HLA-A alleles were typed by molecular techniques. Single nucleotide polymorphism (SNP) genotyping was conducted for 76 MS-associated SNPs and 52 ancestry informative marker SNPs selected throughout the genome. Self-declared ancestry was refined by principal component analysis of the ancestry informative marker SNPs. An ancestry-adjusted multivariate model was applied to assess genetic associations. Results: The following major histocompatibility complex risk alleles were replicated: HLADRB1 15:01 (odds ratio [OR] 5 2.02 [95% confidence interval: 1.54-2.63], p 5 2.50e-07), HLA-DRB1 03:01 (OR 5 1.58 [1.29-1.94], p 5 1.11e-05), as well as HLA-DRB1 04:05 (OR 5 2.35 [1.26-4.37], p 5 0.007) and the African-specific risk allele of HLA-DRB1 15:03 (OR 5 1.26 [1.05-1.51], p 5 0.012). The protective association of HLA-A02:01 was confirmed (OR 5 0.72 [0.55-0.93], p 5 0.013). None of the HLA-DQB1 alleles were associated with MS. Using a significance threshold of p , 0.01, outside the major histocompatibility complex region, 8MS SNPs were also found to be associated with MS in African Americans. Conclusion: MS genetic risk in African Americans only partially overlaps with that of Europeans and could explain the difference of MS prevalence between populations.

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