Genetic susceptibility to multiple sclerosis: interactions between conserved extended haplotypes of the MHC and other susceptibility regions - Centre de Recherche en Transplantation et Immunologie Accéder directement au contenu
Article Dans Une Revue BMC Medical Genomics Année : 2021

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

Résumé

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 +); extendedrisk (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.
Fichier principal
Vignette du fichier
s12920-021-01018-6.pdf (3.93 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

inserm-03313792 , version 1 (04-08-2021)

Identifiants

Citer

D S Goodin, P Khankhanian, P A Gourraud, N Vince. Genetic susceptibility to multiple sclerosis: interactions between conserved extended haplotypes of the MHC and other susceptibility regions. BMC Medical Genomics, 2021, 14 (1), pp.183. ⟨10.1186/s12920-021-01018-6⟩. ⟨inserm-03313792⟩
44 Consultations
28 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More