Multiple sclerosis susceptibility alleles in African Americans
B A Johnson1, J Wang, E M Taylor
1Department of Neurology, University of California, San Francisco, CA 94143, USA.
Genes and Immunity
|October 30, 2009
Summary
Genetic factors influence multiple sclerosis (MS) risk and progression differently across ancestries. This study identified specific genetic variants associated with MS risk in African Americans, confirming shared genetic mechanisms with European populations.
Area of Science:
- Neuroimmunology
- Genetics of Autoimmune Diseases
- Population Health
Background:
- Multiple sclerosis (MS) presents with complex genetic underpinnings and gene-environment interactions.
- African Americans exhibit lower MS incidence but higher disability risk compared to White populations, suggesting potential genetic and environmental disparities.
- Previous studies identified single nucleotide polymorphisms (SNPs) associated with MS risk in White populations.
Purpose of the Study:
- To investigate the association of previously identified MS risk-associated SNPs with MS susceptibility in African Americans.
- To explore potential genetic influences on MS disease characteristics, such as age of onset and progression, in African Americans.
Main Methods:
- A replication study was conducted using 918 MS cases and 656 unrelated controls from an African American cohort.
- Genotyping was performed for SNPs in 12 candidate genes previously implicated in MS risk.
- Statistical analyses were used to assess associations between SNPs and MS risk, age of onset, and disease progression.
Main Results:
- SNPs in CD6, CLEC16a, EVI5, GPC5, and TYK2 were significantly associated with MS risk in the African American cohort.
- The strongest association outside the major histocompatibility complex was observed for EVI5 (rs10735781, OR=1.233, P=0.006).
- RGS1 showed a potential association with age of onset, and TNFRSF1A with disease progression.
- No statistically significant inconsistencies were found between the observed effects in African Americans and those previously established in White populations.
Conclusions:
- The findings support shared genetic mechanisms underlying MS susceptibility across individuals of European and African ancestry.
- Specific genes, including EVI5, contribute to MS risk in African Americans.
- Genetic factors may influence MS disease heterogeneity, including age of onset and progression, across different ancestral groups.
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