RE: “FAMILIAL RISK OF MULTIPLE SCLEROSIS: A NATIONWIDE COHORT STUDY”

In a recent register-based Danish cohort study on multiple sclerosis, Nielsen et al. (1) reported a 7.1-fold increased risk of multiple sclerosis in first-degree relatives of multiple sclerosis patients and an 8.6-fold risk in nontwin siblings. Brothers had a high relative risk of 12.6, as compared with sisters’ risk of 6.3. The study was based on the Danish Multiple Sclerosis Register for diagnostic data and on theDanish Civil Registration System for family data, available for persons born in the early 1950s. No age-specific data were given, but, at least for siblings, the age span was probably about 0–45 years, because follow-up was terminated at the end of 1997. Based on uniform diagnostic data and registers with high coverage, the results of this study would be expected to be highly reliable. They provide further evidence for the heritable etiology of this disease, for which a family history is thought to be present in up to 20 percent of cases (2–4). The possibility of family linkage studies also exists in Sweden through the Multigeneration Register, maintained by Statistics Sweden. This resource has been extensively used in the study of familial cancer, because a nationwide cancer register is available (5). For diseases lacking register data, hospital discharge data can be used—as we have shown, for example, for migraine and other headache syndromes (6). We have also used these resources for the study of multiple sclerosis. We constructed a neurologic disease database through linkage of Swedish Hospital Discharge Register data from 1987 onwards to the Multigeneration Register, which contains data on all persons born in Sweden in 1932 or thereafter and their parents. Sibships were constructed for the generation born after 1931. Dates of hospitalization for multiple sclerosis were obtained for all patients who stayed at least one night in the hospital, usually in wards with specialist consultation or neurology departments; the Register does not include data on hospital outpatients or patients seen at health-care centers. Diagnoses were reported according to the Ninth (1987–1996) and Tenth (1997–2001) Revisions of the International Classification of Diseases. Person-years were calculated from the start of follow-up on January 1, 1987, to hospitalization for multiple sclerosis,