[TMIC] Multiple sclerosis has a clinically significant heritable component

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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.