BACKGROUND: The modulating effects of the multiple sclerosis (MS) risk-associated single-nucleotide polymorphisms (SNPs) on MS clinical course are not well established. OBJECTIVES: The objective of this paper is to investigate whether known MS risk-associated SNPs were associated with clinical course, and whether these SNPs modified the 25(OH)D-relapse association. METHODS: Using a prospective cohort of 141 participants with relapsing-remitting MS and genotype data followed between 2002 and 2005, genotype-vitamin D interactions and the genetic predictors of relapse were assessed using survival analysis, and genetic predictors of 25(OH)D and disability progression were evaluated by multilevel mixed-effects linear regression. RESULTS: While no SNP reached statistical significance after multiple testing, five SNPs were associated with relapse, with significant cumulative genotype risk effects and two demonstrated significant allele dose-response. Two SNPs altered the 25(OH)D-relapse association with significant allele dose-response. Five SNPs modified levels of 25(OH)D, with significant cumulative genotype 'risk' effect, and three demonstrated significant allele dose-response. We found no consistent evidence for an association between any SNPs and disability. CONCLUSIONS: Our study provides evidence for an association between known MS risk-associated SNPs and relapse. Our findings indicate gene-environment interactions may be an important mechanism on MS clinical course, and provide support for the role of vitamin D in MS relapse.
BACKGROUND: The modulating effects of the multiple sclerosis (MS) risk-associated single-nucleotide polymorphisms (SNPs) on MS clinical course are not well established. OBJECTIVES: The objective of this paper is to investigate whether known MS risk-associated SNPs were associated with clinical course, and whether these SNPs modified the 25(OH)D-relapse association. METHODS: Using a prospective cohort of 141 participants with relapsing-remitting MS and genotype data followed between 2002 and 2005, genotype-vitamin D interactions and the genetic predictors of relapse were assessed using survival analysis, and genetic predictors of 25(OH)D and disability progression were evaluated by multilevel mixed-effects linear regression. RESULTS: While no SNP reached statistical significance after multiple testing, five SNPs were associated with relapse, with significant cumulative genotype risk effects and two demonstrated significant allele dose-response. Two SNPs altered the 25(OH)D-relapse association with significant allele dose-response. Five SNPs modified levels of 25(OH)D, with significant cumulative genotype 'risk' effect, and three demonstrated significant allele dose-response. We found no consistent evidence for an association between any SNPs and disability. CONCLUSIONS: Our study provides evidence for an association between known MS risk-associated SNPs and relapse. Our findings indicate gene-environment interactions may be an important mechanism on MS clinical course, and provide support for the role of vitamin D in MS relapse.
Authors: Jennifer S Graves; Lisa F Barcellos; Steve Simpson; Anita Belman; Rui Lin; Bruce V Taylor; Anne-Louise Ponsonby; Terence Dwyer; Lauren Krupp; Emmanuelle Waubant; Ingrid A F van der Mei Journal: Mult Scler Relat Disord Date: 2017-10-14 Impact factor: 4.339
Authors: Jennifer S Graves; Lisa F Barcellos; Xiaorong Shao; Janelle Noble; Ellen M Mowry; Hong Quach; Anita Belman; T Charles Casper; Lauren B Krupp; Emmanuelle Waubant Journal: Mult Scler Date: 2016-01-14 Impact factor: 6.312
Authors: Emmanuelle Waubant; Robyn Lucas; Ellen Mowry; Jennifer Graves; Tomas Olsson; Lars Alfredsson; Annette Langer-Gould Journal: Ann Clin Transl Neurol Date: 2019-08-07 Impact factor: 4.511