Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans
Year: 2020
Type: article
Study design: Observational Study
Abstract: Epidemiological studies have suggested differences in the rate of multiple sclerosis (MS) in individuals of European ancestry compared to African ancestry, motivating genetic scans to identify variants that could contribute to such patterns. In a whole-genome scan in 899 African-American cases and 1155 African-American controls, we confirm that African-Americans who inherit segments of the genome of European ancestry at a chromosome 1 locus are at increased risk for MS [logarithm of odds (LOD) = 9.8], although the signal weakens when adding an additional 406 cases, reflecting heterogeneity in the two sets of cases [logarithm of odds (LOD) = 2.7]. The association in the 899 individuals can be fully explained by two variants previously associated with MS in European ancestry individuals. These variants tag a MS susceptibility haplotype associated with decreased CD58 gene expression (odds ratio of 1.37; frequency of 84% in Europeans and 22% in West Africans for the tagging variant) as well as another haplotype near the FCRL3 gene (odds ratio of 1.07; frequency of 49% in Europeans and 8% in West Africans). Controlling for all other genetic and environmental factors, the two variants predict a 1.44-fold higher rate of MS in European-Americans compared to African-Americans.
Source: Scientific Reports
Institutions: Harvard University, Harvard–MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Broad Institute, Brigham and Women's Hospital, University of California, Berkeley, University of Miami, Kyushu University, University of California, San Francisco, University of California San Francisco Medical Center, Columbia University Irving Medical Center, Yale University, Howard Hughes Medical Institute
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,870
Funders: Howard Hughes Medical Institute, National Multiple Sclerosis Society, University of Miami, Multiple Sclerosis Society, National Institutes of Health, Japan Society for the Promotion of Science, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences
Awards: Genetic and Phenotypic Analysis of Multiple Sclerosis in Hispanics, G3206613393, Medical Scientist Training Program, Parent-of-origin effect in multiple sclerosis susceptibility, Leveraging functional data to predict disease risk in multi-ethnic populations, G4815326608, G6321917404, Yale Clinical and Translational Science Award
OpenAlex ID: W3091832666