A whole genome association study in Icelandic multiple sclerosis patients with 4804 markers.

Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS) with a complex genetic background. Here we use a genome-wide association strategy with 4804 microsatellite markers successfully typed in separately pooled DNA from 200 patients and 200 controls. A total of 91 markers showed evidence of association. When compared to our in-house physical map of the genome, six 2-Mb regions containing at least two of these markers were detected. Of those, three regions have one or more markers among the 20 most strongly associated: chromosomes 3q25, 6p21.3 (the MHC region) and 19q13.

Multiple sclerosis in Iceland from 1900 to 2000: A total population study.

The epidemiology of multiple sclerosis (MS) in Iceland in1900-2000 is presented. The incidence increased significantly from 2.58×10(5) in 1950 to 5.06×10(5) in 2000 (from 2.71 to 7.03×10(5) for women and from 2.55 to 3.10×10(5) for men) with a yearly increase by a factor of 1.0816 per year for women and 1.01207 per year for men (Poisson regression analysis). Prevalence standardized to the European standard population rose from 29.9×10(5) in 1950 to 131.7×10(5) in 2000. The standardized prevalence was constantly higher amongst women (42.8-181.6×10(5) vs. 16.7-81.5×10(5) for men) with a female to male ratio of 2.6 in 1950 and in 2000. Mean age at onset for all patients increased from 27.8 years in 1950 to 30.7 years in 2000 (from 27.0 to 30.1 years for women and from 28.6 to 32.2 years for men). Children and adolescents (<18 years) were 9.6% of all, of whom 60% were diagnosed after 1970. Mean age of onset for children and adolescents was 14.7 years (9-17 years, 95% CI 4.2 years). The rise in incidence and prevalence can have multiple explanations, including diagnosis of milder forms of MS, increased awareness of MS in the older population, better diagnostic measures and longer survival but the authors find it likely that there has been a true rise in the MS incidence.

Variant in the sequence of the LINGO1 gene confers risk of essential tremor.

We identified a marker in LINGO1 showing genome-wide significant association (P = 1.2 x 10(-9), odds ratio = 1.55) with essential tremor. LINGO1 has potent, negative regulatory influences on neuronal survival and is also important in regulating both central-nervous-system axon regeneration and oligodendrocyte maturation. Increased axon integrity observed in Lingo1 mouse [corrected] knockout models highlights the potential role of LINGO1 in the pathophysiology of ET [corrected]

[Prevalence of myotonic dystrophy in Iceland]. / Spennuvisnun (Dystrophia Myotonica): almennt yfirlit og algengi á Islandi.

OBJECTIVE: Epidemiologic studies of Myotonic Dystrophy (Dystrophic Myotony, DM) have shown variable regional prevalence from 0,46 to 189/105. We carried out a total population survey of DM in Iceland in 2004 having Oct. 31 as the day of prevalence. MATERIAL AND METHODS: Patients were collected from multiple sources, including Landspitali University Hospital registry and through contact with neurologists, neuropaediatricians, paediatricians and rehabilitation specialists. All EMGs of DM patients were reviewed. Information was gathered about age, age of onset, family history of DM and clinical symptoms. RESULTS: Eighty-two patients were ascertained giving a crude prevalence of 28.2/105. The prevalence of the congenital form of DM was 7.9/105 (23 patients, 26%). Affected females outnumbered males with a gender ratio of 1.2:1 (NS). Mean age of onset of symptoms for those, who didn't have the congenital form was 27.5 years (range 5-70 years). Ten families with DM were identified and all prevalent patients belonged to those families. CONCLUSION: The prevalence of DM is high in Iceland and higher than generally reported. This study showed a three times higher total prevalence and a seven times higher prevalence of congenital DM than found in a previous study in Iceland. We believe that this increase in prevalence probably reflects increased awareness of inherited diseases in neonates and better detection of patients who have mild symptoms.

Localization of a gene for migraine without aura to chromosome 4q21.

Migraine is a common form of headache and has a significant genetic component. Here, we report linkage results from a study in Iceland of migraine without aura (MO). The study group comprised patients with migraine recruited by neurologists and from the registry of the Icelandic Migraine Society, as well as through the use of a questionnaire sent to a random sample of 20,000 Icelanders. Migraine diagnoses were made and confirmed using diagnostic criteria established by the International Headache Society. A genome-wide scan with multipoint allele-sharing methods was performed on 289 patients suffering from MO. Linkage was observed to a locus on chromosome 4q21 (LOD=2.05; P=.001). The locus reported here overlaps a locus (MGR1) reported elsewhere for patients with migraine with aura (MA) in the Finnish population. This replication of the MGR1 locus in families with MO indicates that the gene we have mapped may contribute to both MA and MO. Further analysis indicates that the linkage evidence improves for affected females and, especially, with a slightly relaxed definition of MO (LOD=4.08; P=7.2 x 10(-6)).