NeuroTalk Support Groups - NEJM: Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study

Hi -

I post over on the RSD board, but these popped up on line today - Sunday - from the New England Journal of Medicine, posted ahead of the usual Thursday publication date.

"Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study," The International Multiple Sclerosis Genetics Consortium, published at www.nejm.org July 29, 2007 (10.1056/NEJMoa073493) which you can directly download here: http://content.nejm.org/cgi/content/...3493?query=TOC

The article abstract follows:

ABSTRACT

Background Multiple sclerosis has a clinically significant heritable component. We conducted a genomewide association study to identify alleles associated with the risk of multiple sclerosis.

Methods We used DNA microarray technology to identify common DNA sequence variants in 931 family trios (consisting of an affected child and both parents) and tested them for association. For replication, we genotyped another 609 family trios, 2322 case subjects, and 789 control subjects and used genotyping data from two external control data sets. A joint analysis of data from 12,360 subjects was performed to estimate the overall significance and effect size of associations between alleles and the risk of multiple sclerosis.

Results A transmission disequilibrium test of 334,923 single-nucleotide polymorphisms (SNPs) in 931 family trios revealed 49 SNPs having an association with multiple sclerosis (P<1x10–4); of these SNPs, 38 were selected for the second-stage analysis. A comparison between the 931 case subjects from the family trios and 2431 control subjects identified an additional nonoverlapping 32 SNPs (P<0.001). An additional 40 SNPs with less stringent P values (<0.01) were also selected, for a total of 110 SNPs for the second-stage analysis. Of these SNPs, two within the interleukin-2 receptor gene (IL2RA) were strongly associated with multiple sclerosis (P=2.96x10–8), as were a nonsynonymous SNP in the interleukin-7 receptor gene (IL7RA) (P=2.94x10–7) and multiple SNPs in the HLA-DRA locus (P=8.94x10–81).

Conclusions Alleles of IL2RA and IL7RA and those in the HLA locus are identified as heritable risk factors for multiple sclerosis.

There's also a related editorial "Old Suspects Found Guilty — The First Genome Profile of Multiple Sclerosis," which closes by noting "Without a doubt, the multiple sclerosis community will soon be informed about the systematic scans for copy-number variations or other more complex changes in the genomic architecture of risk alleles for multiple sclerosis," at: http://content.nejm.org/cgi/content/...8147?query=TOC

As happens on occasion with matters of special significance, both articles are available to the public at no charge, although free online registration may be required. Once you get there, you can also download .pdf copies of both files.

be well,
Mike