Genetic susceptibility to multiple sclerosis: interactions between conserved extended haplotypes of the MHC and other susceptibility regions.
In: BMC medical genomics, Jg. 14 (2021-07-10), Heft 1
Online
academicJournal
- 183
BackgroundTo 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.MethodsThe 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.ResultsDifferent 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.ConclusionsGenetic-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.
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Genetic susceptibility to multiple sclerosis: interactions between conserved extended haplotypes of the MHC and other susceptibility regions.
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Autor/in / Beteiligte Person: | Goodin, DS ; Khankhanian, P ; Gourraud, PA ; Vince, N |
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Zeitschrift: | BMC medical genomics, Jg. 14 (2021-07-10), Heft 1 |
Veröffentlichung: | eScholarship, University of California, 2021 |
Medientyp: | academicJournal |
Umfang: | 183 |
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