Burden of genetic risk variants in multiple sclerosis families in the Netherlands.

BACKGROUND

Approximately 20% of multiple sclerosis patients have a family history of multiple sclerosis. Studies of multiple sclerosis aggregation in families are inconclusive.

OBJECTIVE

To investigate the genetic burden based on currently discovered genetic variants for multiple sclerosis risk in patients from Dutch multiple sclerosis multiplex families versus sporadic multiple sclerosis cases, and to study its influence on clinical phenotype and disease prediction.

METHODS

Our study population consisted of 283 sporadic multiple sclerosis cases, 169 probands from multiplex families and 2028 controls. A weighted genetic risk score based on 102 non-human leukocyte antigen loci and was calculated.

RESULTS

The weighted genetic risk score based on all loci was significantly higher in familial than in sporadic cases. The contributed significantly to the difference in genetic burden between the groups. A high weighted genetic risk score was significantly associated with a low age of disease onset in all multiple sclerosis patients, but not in the familial cases separately. The genetic risk score was significantly but modestly better in discriminating familial versus sporadic multiple sclerosis from controls.

CONCLUSION

Familial multiple sclerosis patients are more loaded with the common genetic variants than sporadic cases. The difference is mainly driven by . The predictive capacity of genetic loci is poor and unlikely to be useful in clinical settings.