Familial risk of early- and late-onset multiple sclerosis: a Swedish nationwide study

Ali Manouchehrinia,Jan Hillert,Ingrid Kockum,Kyla A Mckay,Pernilla Stridh,Helga Westerlind,Catarina Almqvist,Jie Song

doi:10.1007/s00415-018-9163-6

Ali Manouchehrinia, Jan Hillert + Show 6 more

Open Access

https://doi.org/10.1007/s00415-018-9163-6

Copy DOI

Abstract

BackgroundPersons who develop multiple sclerosis (MS) at a young age may bear a higher genetic risk load than persons who develop MS later in life; however, the contribution of familial influence to the risk of MS, in relation to onset age, has not been established.ObjectiveTo investigate the familial risk of MS at two extremes of the spectrum of MS onset age: early onset (first MS symptom < 18 years of age) and late onset (first MS symptom ≥ 50 years).MethodsNationwide registries in Sweden were used to identify cases of MS and controls, and their familial relations. We estimated the odds ratio (OR) of an MS diagnosis for individuals with a relative diagnosed with early-onset or late-onset MS compared with those whose relatives did not have MS, using a nested case–control design.Results629 early-onset and 1148 late-onset MS patients were identified and matched to 10 controls from the general population by age and sex. The OR of MS for individuals with a first-degree relative diagnosed with early-onset MS was 10.86 (95% CI 6.87–17.17); and for late-onset MS was 8.08 (95% CI 6.12–10.67).ConclusionsOur findings demonstrate no substantial differences in familial risk in persons with early- and late-onset MS.

Highlights

The underlying aetiology of multiple sclerosis (MS) is unknown, but likely involves an interaction between genes and environment [1]
We identified 629 patients with an MS onset before age 18 (EOMS) and 1148 whose onset age was greater than or equal to 50 years (LOMS) from the Swedish MS Register (SMSreg)
A higher familial risk is thought to compensate for the shorter time of exposure to the environmental trigger(s) in early-onset MS (EOMS) patients

Summary

Introduction

The underlying aetiology of multiple sclerosis (MS) is unknown, but likely involves an interaction between genes and environment [1]. The genetic risk of the disease appears to be largely driven by alleles controlling the human leukocyte antigen (HLA) system. Though not considered a hereditary disease, MS can aggregate in families and the estimated recurrence risks for MS in Sweden are 17.3% for monozygotic twins and 2.6% for siblings [5]. Persons who develop multiple sclerosis (MS) at a young age may bear a higher genetic risk load than persons who develop MS later in life; the contribution of familial influence to the risk of MS, in relation to onset age, has not been established. Results 629 early-onset and 1148 late-onset MS patients were identified and matched to 10 controls from the general population by age and sex.

Methods

Results

Conclusion