No evidence of association between mutant alleles of the CYP27B1 gene and multiple sclerosis

Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
Annals of Neurology (Impact Factor: 9.98). 03/2013; 73(3). DOI: 10.1002/ana.23833
Source: PubMed


An association has previously been reported between susceptibility to multiple sclerosis and the rare mutant alleles of the CYP27B1 gene responsible for autosomal recessive vitamin D-dependent rickets type 1 (VDDR1). In an attempt to replicate this finding, we screened 495 multiplex families and 2,092 single affected families, together with 4,594 cases and 3,583 controls (a total of 17,073 individuals) but were unable to find any evidence supporting this putative association. Our data do not indicate that mutations responsible for VDDR1 influence the risk of developing multiple sclerosis. Ann Neurol 2013;

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Available from: Kjell-Morten Myhr, Dec 01, 2014
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    • "As GWAS loci presumably have a higher probability of harboring rare, deleterious alleles than the rest of the genome, the authors concluded that rare variants unlikely account for a substantial fraction of missing heritability in autoimmune diseases (17). Along these lines, an initial report (18) of a rare, high-risk MS variant in the vitamin-D activating gene CYP27B1 was not confirmed in independent validation studies (19, 20). Future genome-wide studies need to test massive sample sizes, comparable with those used in recent GWAS, to conclusively assess the potential role of rare variants in MS. "
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