The genetic diversity of multiple sclerosis risk among Hispanic and African American populations living in the United States.
Multiple sclerosis
admixture
allelic heterogeneity
genetics
locus heterogeneity
multi-ethnic
pathway analysis
risk score
Journal
Multiple sclerosis (Houndmills, Basingstoke, England)
ISSN: 1477-0970
Titre abrégé: Mult Scler
Pays: England
ID NLM: 9509185
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
pubmed:
2
8
2019
medline:
25
9
2021
entrez:
2
8
2019
Statut:
ppublish
Résumé
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 ( 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.
Sections du résumé
BACKGROUND
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.
OBJECTIVE
We sought to test the relevance of common European MS risk variants outside of the major histocompatibility complex (
METHODS
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.
RESULTS
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.
CONCLUSION
These findings provide a framework for fine-mapping efforts in multi-ethnic populations of MS.
Identifiants
pubmed: 31368393
doi: 10.1177/1352458519863764
pmc: PMC6994382
mid: NIHMS1532805
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1329-1339Subventions
Organisme : NINDS NIH HHS
ID : R01 NS096212
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR000131
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS082347
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001855
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS026799
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL102487
Pays : United States
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