Differential twin concordance for multiple sclerosis by latitude of birthplace

Objective: To address the inconsistency in the reported concordance of multiple sclerosis (MS) among twins by zygosity, sex, and latitude. Methods: Four hundred eighteen medically documented monozygotic (MZ) and 380 same-sex dizygotic (DZ) pairs were ascertained from 1980 to 1992 and followed. The study population was representative of twins with multiple sclerosis. Twins from Canada and adjacent US states (at or above 41-42 degrees N) were considered northern, and ancestry was dichotomized from descent from high-risk populations. Diagnosis before median age 29.3 years was considered early. Results: The MZ/DZ concordance ratio was 2.9 (95% confidence interval [CI], 1.0-8.9) among men and 2.6 (95% Cl, 1.5-4.5) among women. The average age at northern diagnosis was independent of ancestry and 2 years earlier for both MZ (p < 0.02) and DZ (p < 0.01) patients. Among DZ twins, concordance was independent of all characteristics. Among MZ twins, concordance was 1.9 times (95% Cl, 1.2-3.2) greater among northern twins, 1.9 (95% Cl, 1.1-3.6) times greater among twins with high-risk ancestry, and 2.1 (95% Cl, 1.2-3.6) times greater if diagnosis was early. Ancestry and early diagnosis made independent significant contributions to the differential concordance by latitude. Interpretation: Multiple sclerosis is similarly heritable by sex, and the apparent variation in MZ concordance by latitude is influenced by environmental and genetic factors.