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The genetic diversity of multiple sclerosis risk among Hispanic and African American populations living in the United States.

Authors
  • Beecham, A H1
  • Amezcua, L2
  • Chinea, A3
  • Manrique, C P4
  • Rubi, C3
  • Isobe, N5
  • Lund, B T2
  • Santaniello, A6
  • Beecham, G W1
  • Burchard, E G7
  • Comabella, M8
  • Patsopoulos, N9
  • Fitzgerald, K10
  • Calabresi, P A10
  • De Jager, P11
  • Conti, D V12
  • Delgado, S R13
  • Oksenberg, J R6
  • McCauley, J L1
  • 1 John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA/The Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA.
  • 2 Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • 3 San Juan MS Center, Guaynabo, Puerto Rico, USA; Universidad Central del Caribe, Bayamon, Puerto Rico, USA. , (Puerto Rico)
  • 4 John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
  • 5 Department of Neurological Therapeutics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. , (Japan)
  • 6 Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
  • 7 Departments of Medicine and Bioengineering and Therapeutic Sciences, University of California at San Francisco, San Francisco, CA, USA.
  • 8 Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. , (Spain)
  • 9 Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • 10 Department of Neurology and The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 11 Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, USA.
  • 12 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • 13 Multiple Sclerosis Division, Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.
Type
Published Article
Journal
Multiple sclerosis (Houndmills, Basingstoke, England)
Publication Date
Aug 01, 2019
Identifiers
DOI: 10.1177/1352458519863764
PMID: 31368393
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Substantial progress has been made toward unraveling the genetic architecture of multiple sclerosis (MS) within populations of European ancestry, but few genetic studies have focused on Hispanic and African American populations within the United States. We sought to test the relevance of common European MS risk variants outside of the major histocompatibility complex (n = 200) within these populations. Genotype data were available on 2652 Hispanics (1298 with MS, 1354 controls) and 2435 African Americans (1298 with MS, 1137 controls). We conducted single variant, pathway, and cumulative genetic risk score analyses. We found less replication than statistical power suggested, particularly among African Americans. This could be due to limited correlation between the tested and causal variants within the sample or alternatively could indicate allelic and locus heterogeneity. Differences were observed between pathways enriched among the replicating versus all 200 variants. Although these differences should be examined in larger samples, a potential role exists for gene-environment or gene-gene interactions which alter phenotype differentially across racial and ethnic groups. Cumulative genetic risk scores were associated with MS within each study sample but showed limited diagnostic capability. These findings provide a framework for fine-mapping efforts in multi-ethnic populations of MS.

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