Risk for multiple sclerosis in relatives and spouses of patients diagnosed with autoimmune and related conditions

In the era of complex disease genetics, the consideration of familial risks is important in the assessment of the likely success of these studies. In the present article, we study familial risks for multiple sclerosis (MS) among parents and offspring, singleton siblings, twins, and spouses when a family member was diagnosed with MS or any of 33 other autoimmune diseases. The availability of a Multigeneration Register in Sweden provides a reliable access to families throughout the last century. The diseases in individual family members were obtained through linkage to the Hospital Discharge Register. With a total patient population of 425,102 of whom 11,154 were diagnosed with MS, this is the largest population-based family study on these diseases to date. Standardized incidence ratio (SIR) was calculated for family member of MS patients compared to those lacking an affected family member. SIR for MS was 5.94 (6.12 when parents were aged <73 years) in offspring of affected parents, 6.25 in singleton siblings, 9.09 in twins, and 1.50 (nonsignificant) in spouses; the SIRs did not depend on the gender. The SIRs for MS were 1.84 when a parent was diagnosed with amyotrophic lateral sclerosis and 1.14 with parental asthma. The overall risk of MS was 1.21 when a parent was diagnosed with any autoimmune disease. The genes, so far associated with MS, explain little of the familial aggregation of MS, calling for further efforts in gene identification. The shared familial risks of MS with amyotrophic lateral sclerosis and asthma suggest shared genetic basis.