Is the genetic susceptibility to MS in African-Americans different to Europeans?

Why are African-Americans susceptible to MS? #MSBlog #MSResearch

“The following study looked to see if the genetic risk of MS in African Americans was different to that of people of European descent. As you are aware man migrated out of Africa about 60,000 years ago and in that time a lot of genetic variation / selection took place to give rise to modern Europeans. There is genetic, linguistic (language) and archeological evidence that there were at least 3 and possibly 4 waves of migration of modern man into Europe. During this time European man interbred with Neanderthals and was exposed to a very different  environment that resulted in natural selection. The result is there are genetic differences between Africans and Europeans. The question then are different genes, or genetic variants, responsible for MS risk different between Americans of European or African descent? The study below suggest not. The majority of the susceptibility variants are shared between African-Americans and European-Americans. Interestingly, variability around some of these variants suggest they are not due genetic admixture (interbreeding) and reassuringly imply that these variants must be relevant to the biology of MS.”

“Some susceptibility variants found appear to be unique to African-Americans, but need to be confirmed. These results indicate that although the genetic susceptibility to MS is complex there is a common set of pathways that dictate risk across populations. It is therefore important to examine these biological pathways to see how they interact with known environmental factors so that we can pin-down the cause of MS. For example, some of the pathways identified are involved in B cell biology supporting this cell as being important, and possibly pivotal, in MS.”

Map of the migration of modern humans out of Africa, based on mitochondrial DNA. Colored rings indicate thousand years before present. From Wikipedia.

“You may be interested to know that I have been searching the literature intermittently for over 15 years looking for a case report, or reports, of  MS occurring in people with rare hereditary causes of B cell deficiencies. As of yet I have not found a report. Is this telling us something? If you know of someone with an hereditary defect in B cell function and a diagnosis of MS please let me know. Thanks.”

Epub: Isobe et al. An ImmunoChip study of multiple sclerosis risk in African Americans. Brain. 2015. pii: awv078.

Background: 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. 

Methods: Using the ImmunoChip custom array we genotyped 803 African American cases with MS 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. 

Results: Of the 110 non-major histocompatibility complex MS-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 MS 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). 

Conclusion: Our data demonstrate substantial overlap between African American and European MS variants, indicating common genetic contributions to multiple sclerosis risk. 

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