An ImmunoChip study of multiple sclerosis risk in African Americans

Noriko Isobe, Lohith Madireddy, Pouya Khankhanian, Takuya Matsushita, Stacy J. Caillier, Jayaji M. Moré, Pierre Antoine Gourraud, Jacob L. McCauley, Ashley H. Beecham, Laura Piccio, Joseph Herbert, Omar Khan, Jeffrey Cohen, Lael Stone, Adam Santaniello, Bruce A.C. Cree, Suna Onengut-Gumuscu, Stephen S. Rich, Stephen L. Hauser, Stephen SawcerJorge R. Oksenberg

    Research output: Contribution to journalArticle

    30 Citations (Scopus)

    Abstract

    The aims of this study were: (i) to determine to what degree multiple sclerosis-associated loci discovered in European populations also influence susceptibility in African Americans; (ii) to assess the extent to which the unique linkage disequilibrium patterns in African Americans can contribute to localizing the functionally relevant regions or genes; and (iii) to search for novel African American multiple sclerosis-associated loci. Using the ImmunoChip custom array we genotyped 803 African American cases with multiple sclerosis and 1516 African American control subjects at 130 135 autosomal single nucleotide polymorphisms. We conducted association analysis with rigorous adjustments for population stratification and admixture. Of the 110 non-major histocompatibility complex multiple sclerosis-associated variants identified in Europeans, 96 passed stringent quality control in our African American data set and of these, >70% (69) showed over-representation of the same allele amongst cases, including 21 with nominally significant evidence for association (one-tailed test P<0.05). At a further eight loci we found nominally significant association with an alternate correlated risk-tagging single nucleotide polymorphism from the same region. Outside the regions known to be associated in Europeans, we found seven potentially associated novel candidate multiple sclerosis variants (P<10-4), one of which (rs2702180) also showed nominally significant evidence for association (one-tailed test P = 0.034) in an independent second cohort of 620 African American cases and 1565 control subjects. However, none of these novel associations reached genome-wide significance (combined P = 6.3 × 10-5). Our data demonstrate substantial overlap between African American and European multiple sclerosis variants, indicating common genetic contributions to multiple sclerosis risk.

    Original languageEnglish
    Pages (from-to)1518-1530
    Number of pages13
    JournalBrain
    Volume138
    Issue number6
    DOIs
    Publication statusPublished - Jun 1 2015

    Fingerprint

    African Americans
    Multiple Sclerosis
    Single Nucleotide Polymorphism
    Linkage Disequilibrium
    Major Histocompatibility Complex
    Quality Control
    Population
    Alleles
    Genome
    Genes

    All Science Journal Classification (ASJC) codes

    • Clinical Neurology

    Cite this

    Isobe, N., Madireddy, L., Khankhanian, P., Matsushita, T., Caillier, S. J., Moré, J. M., ... Oksenberg, J. R. (2015). An ImmunoChip study of multiple sclerosis risk in African Americans. Brain, 138(6), 1518-1530. https://doi.org/10.1093/brain/awv078

    An ImmunoChip study of multiple sclerosis risk in African Americans. / Isobe, Noriko; Madireddy, Lohith; Khankhanian, Pouya; Matsushita, Takuya; Caillier, Stacy J.; Moré, Jayaji M.; Gourraud, Pierre Antoine; McCauley, Jacob L.; Beecham, Ashley H.; Piccio, Laura; Herbert, Joseph; Khan, Omar; Cohen, Jeffrey; Stone, Lael; Santaniello, Adam; Cree, Bruce A.C.; Onengut-Gumuscu, Suna; Rich, Stephen S.; Hauser, Stephen L.; Sawcer, Stephen; Oksenberg, Jorge R.

    In: Brain, Vol. 138, No. 6, 01.06.2015, p. 1518-1530.

    Research output: Contribution to journalArticle

    Isobe, N, Madireddy, L, Khankhanian, P, Matsushita, T, Caillier, SJ, Moré, JM, Gourraud, PA, McCauley, JL, Beecham, AH, Piccio, L, Herbert, J, Khan, O, Cohen, J, Stone, L, Santaniello, A, Cree, BAC, Onengut-Gumuscu, S, Rich, SS, Hauser, SL, Sawcer, S & Oksenberg, JR 2015, 'An ImmunoChip study of multiple sclerosis risk in African Americans', Brain, vol. 138, no. 6, pp. 1518-1530. https://doi.org/10.1093/brain/awv078
    Isobe N, Madireddy L, Khankhanian P, Matsushita T, Caillier SJ, Moré JM et al. An ImmunoChip study of multiple sclerosis risk in African Americans. Brain. 2015 Jun 1;138(6):1518-1530. https://doi.org/10.1093/brain/awv078
    Isobe, Noriko ; Madireddy, Lohith ; Khankhanian, Pouya ; Matsushita, Takuya ; Caillier, Stacy J. ; Moré, Jayaji M. ; Gourraud, Pierre Antoine ; McCauley, Jacob L. ; Beecham, Ashley H. ; Piccio, Laura ; Herbert, Joseph ; Khan, Omar ; Cohen, Jeffrey ; Stone, Lael ; Santaniello, Adam ; Cree, Bruce A.C. ; Onengut-Gumuscu, Suna ; Rich, Stephen S. ; Hauser, Stephen L. ; Sawcer, Stephen ; Oksenberg, Jorge R. / An ImmunoChip study of multiple sclerosis risk in African Americans. In: Brain. 2015 ; Vol. 138, No. 6. pp. 1518-1530.
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    AU - Caillier, Stacy J.

    AU - Moré, Jayaji M.

    AU - Gourraud, Pierre Antoine

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