Concordance and heritability of multiple sclerosis in Finland: study on a nationwide series of twins H. Kuusisto a , J. Kaprio b,c , E. Kinnunen d , T. Luukkaala e,f , M. Koskenvuo b and I. Elovaara a,g a Department of Neurology and Rehabilitation, Tampere University Hospital, Tampere, Finland; b Department of Public Health, University of Helsinki, Helsinki, Finland; c Department of Mental Health and Alcohol Research, National Public Health Research, Helsinki, Finland; d Department of Neurology, Hyvinka ¨a ¨ Hospital, Hyvinka ¨a ¨, Finland; e Research Unit, Tampere University Hospital, Tampere, Finland; f Tampere School of Public Health, University of Tampere, Tampere, Finland; and g Medical School, University of Tampere, Tampere, Finland Keywords: concordance, epidemio- logy, multiple sclerosis, twins Received 25 January 2008 Accepted 26 June 2008 Objectives: To evaluate the changes in the multiple sclerosis (MS) concordance in twins, and the contribution of genetic and environmental factors to the aetiology of MS in Finland. Background: Both genes and the environment contribute to the development of MS. A well-conducted twin study is an excellent means to assess the relative contribution of heritability and environmental factors. Methods: Multiple sclerosis concordance was assessed for 10 Monozygotic and 14 dizygotic twin pairs using pairwise and probandwise concordance rates. The tetrachoric correlations in liability to disease for twin pairs were computed and a polygenic multifactorial model was used to estimate heritability. Results: The pairwise concordance for MZ twins was 30% and for the DZ twins 14.3%, compared with 30% for MZ and 0% for DZ 20 years ago. The corresponding probandwise concordance rates were 46.2% and 25%. The genetic variance (heritability) was 15.3% (95% Cl 0.0–77.6), the common environmental variance 73.7% (95% Cl 14.1–93.9) and the unique environmental variance 11.1% (95% Cl 2.3–30.0). Conclusions: As the concordance of MS in DZ twins has increased during the past two decades and the heritability estimate is low, it seems that the reported increase in MS incidence in Finland is mainly caused by environmental factors. Introduction One of the hallmarks in prevalence of multiple sclerosis (MS) is its uneven geographical distribution classified as low (<5/100 000), medium (5–30/100 000) and high (>30/100 000) prevalence areas [1]. The prevalence of MS in selected parts of Finland is as high as 100–200/ 100 000 [2]. Over the last decades the incidence of MS in Finland has reportedly increased. A recent study found an annual incidence of 5/100 000 [3]. The underlying reason for this increase is obscure, although environmental factors have been proposed [2]. Both genetic and non-genetic factors seem to con- tribute to the susceptibility of MS. Monozygotic (MZ) concordance in high prevalence areas is approximately 25–30% with rates of 3–5% for dizygotic (DZ) pairs, emphasizing the role of genetic factors [4–8]. In medium prevalence regions, however, the twin concordance appears to be significantly lower and similar in MZ and DZ twins implicating that these rates might be related to the background prevalence [9–11]. Therefore, it has been hypothesized that genetic and environmental fac- tors may have varying impact on the susceptibility to MS in different populations [10]. In the previous study of the old Finnish Twin Cohort of like-sexed pairs, the pairwise MS concordance was 29% amongst MZ and 0% amongst DZ twins [12]. To study the relative contribution of genetic and environ- mental factors to MS and the changes in the MS con- cordance in Finland, we conducted the present study, which is based on updated registry linkage of the old Finnish Twin Cohort. Subjects and methods Recruitment of the twins The older Finnish Twin Cohort of like-sexed twins in- cludes all living Finnish twins born 1957 or before [13]. In the 1990s, we updated the earlier cohort of only like- sexed pairs to also include opposite sex-pairs in the birth years 1938–1949 based on a questionnaire survey and registry linkage for opposite-sex pairs born 1950– 1957 [14]. In 2001, there were 3083 MZ and 11 029 DZ same-sex and opposite-sex twin pairs in the cohort. Based on this, the same-sex DZ/MZ ratio was over 3:1 in general population of the same age, which reflects the Correspondence: Hanna Kuusisto, MD, Department of Neurology and rehabilitation, University Hospital of Tampere, PL 2000, 33521 Tampere, Finland (tel.: +358 40 7751595 or +358 3 31164469; fax: +358 3 31164351; e-mail: hanna.kuusisto@pshp.fi 1106 Ó 2008 The Author(s) Journal compilation Ó 2008 EFNS European Journal of Neurology 2008, 15: 1106–1110 doi:10.1111/j.1468-1331.2008.02262.x