Genetic susceptibility to multiple sclerosis: interactions between conserved extended haplotypes of the MHC and other susceptibility regions

2Citations
Citations of this article
18Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Background: To study the accumulation of MS-risk resulting from different combinations of MS-associated conserved-extended-haplotypes (CEHs) of the MHC and three non-MHC “risk-haplotypes” nearby genes EOMES, ZFP36L1, and CLEC16A. Many haplotypes are MS-associated despite having population-frequencies exceeding the percentage of genetically-susceptible individuals. The basis of this frequency-disparity requires explanation. Methods: The SNP-data from the WTCCC was phased at the MHC and three non-MHC susceptibility-regions. CEHs at the MHC were classified into five haplotype-groups: (HLA-DRB1*15:01 ~ DQB1*06:02 ~ a1)-containing (H +); extended-risk (ER); all-protective (AP); neutral (0); and the single-CEH (c1). MS-associations for different “risk-combinations” at the MHC and other non-MHC “risk-loci” and the appropriateness of additive and multiplicative risk-accumulation models were assessed. Results: Different combinations of “risk-haplotypes” produce a final MS-risk closer to additive rather than multiplicative risk-models but neither model was consistent. Thus, (H +)-haplotypes had greater impact when combined with (0)-haplotypes than with (H +)-haplotypes, whereas, (H +)-haplotypes had greater impact when combined with a (c1)-haplotypes than with (0)-haplotypes. Similarly, risk-genotypes (0,H +), (c1,H +), (H + ,H +) and (0,c1) were additive with risks from non-MHC risk-loci, whereas risk-genotypes (ER,H +) and (AP,c1) were unaffected. Conclusions: Genetic-susceptibility to MS is essential for MS to develop but actually developing MS depends heavily upon both an individual’s particular combination of “risk-haplotypes” and how these loci interact.

Cite

CITATION STYLE

APA

Goodin, D. S., Khankhanian, P., Gourraud, P. A., & Vince, N. (2021). Genetic susceptibility to multiple sclerosis: interactions between conserved extended haplotypes of the MHC and other susceptibility regions. BMC Medical Genomics, 14(1). https://doi.org/10.1186/s12920-021-01018-6

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free