Genomewide association study of a homogeneous multiple sclerosis cohort: Tumefactive demyelination.

BACKGROUND

Tumefactive demyelination (TD) is a rare variant of multiple sclerosis (MS) characterized by tumor-like lesions that often require aggressive management. Genome-wide association studies (GWAS) identified variants associated with MS; similar analyses in TD are lacking.

OBJECTIVE

A GWAS was performed to identify variants associated with TD.

METHODS

The case-control study included 142 TD cases and 293 controls. TD patients were required to have a demyelinating event and magnetic resonance imaging (MRI) showing one or more lesions. Controls were patients without a neurologic or systemic inflammatory disease or cancer. Logistic regression was used to compare cases versus controls for each variant; age, sex, and principal components were included as covariates. A p-value threshold of 5 × 10-8 was GWAS significant and 5 × 10-6 nominally significant. A polygenic risk score (PRS) was compared across TD and controls.

RESULTS

Variants on chromosome 14 (rs117797734, p = 2.06 × 10-11, odds ratio (OR) = 13.14) and chromosome 6 (most significant rs6936540, p = 5.5 × 10-7, OR = 2.61) near DCBLD1 were significant. Seven non-MHC and two MHC variants associated with MS were associated with TD. The PRS was significantly higher in TD versus controls.

CONCLUSION

We identified novel regions associated with TD, demonstrating the importance of performing GWAS in homogeneous subtypes of MS. Further validation and functional experiments are necessary.