Finnbogi Jakobsson

The gene encoding phosphodiesterase 4D confers risk of ischemic stroke

We previously mapped susceptibility to stroke to chromosome 5q12. Here we finely mapped this locus and tested it for association with stroke. We found the strongest association in the gene encoding phosphodiesterase 4D (PDE4D), especially for carotid and cardiogenic stroke, the forms of stroke related to atherosclerosis. Notably, we found that haplotypes can be classified into three distinct groups: wild-type, at-risk and protective. We also observed a substantial disregulation of multiple PDE4D isoforms in affected individuals. We propose that PDE4D is involved in the pathogenesis of stroke, possibly through atherosclerosis, which is the primary pathological process underlying ischemic stroke.

Genome-wide meta-analysis identifies new susceptibility loci for migraine

Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P < 5 × 10−8). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B.

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]We identified a marker in LINGO1 showing genome-wide significant association (P = 1.2 × 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 knockout models highlights the potential role of LINGO1 in the pathophysiology of essential tremor.

Torsin A haplotype predisposes to idiopathic dystonia

Previous work has suggested that in many neurological diseases genetic variability in the loci predisposing subjects to autosomal dominant disease contributes to the risk of sporadic disease. Here, using a population‐based sample of dystonia cases, we show an association with the torsin A haplotype and sporadic idiopathic dystonia. Ann Neurol 2005;57:765–767

Prevalence study of primary dystonia in Iceland

In Iceland, the crude prevalence for all types of primary dystonia was 37.1/105 (confidence interval, 30.4–44.9). Focal dystonia had the highest prevalence (31.2/105), followed by segmental (3.1/105), multifocal (2.4/105) and generalized dystonia (0.3/105). Cervical dystonia was the most common focal dystonia (11.5/105), followed by limb dystonia (8.0/105), laryngeal dystonia (5.9/105), blepharospasm (3.1/105), and oromandibular dystonia (2.8/105). The male:female ratio for all patients was 1:1.9 (P = 0.0007), and females outnumbered males in all subtypes except oromandibular dystonia. Mean age of onset for all patients was 42.7 years (range, 3–82 years). This prevalence of primary dystonia is higher than in most reported studies, possibly because of more complete ascertainment but the relative frequencies of dystonia subtypes is similar.

Prevalence of symptomatic Charcot-Marie-Tooth disease in Iceland: a study of a well-defined population.

Background/Aim: To determine the prevalence and clinical spectrum of Charcot-Marie-Tooth disease (CMT) in Iceland. Methods: We identified all individuals with symptomatic CMT, based on information from all practicing neurologists, both neurophysiology laboratories and the only neurology department in the country. The diagnosis was based on clinical features and neurophysiological testing. DNA testing was regarded as confirmatory. Results: We identified 37 individuals in 18 families, which were not linked by identifying 5 generations of ancestors. The point prevalence (January 1, 2007) for all CMT subtypes in Iceland was 12.0/105, 10.1/105 for CMT1 and 2.0/105 for CMT2. The clinical features include lower limb weakness (95%), impaired gait (68%), decreased or absent deep tendon reflexes (86%), pes cavus (70%) and hammer toes (46%). Clinical symptoms were similar for the 2 main CMT subtypes. Conclusion: We report the prevalence and clinical spectrum of CMT, which is comparable to the results of other prevalence studies, in a well-defined, total population sample.

Incidence and outcome of Guillain‐Barré syndrome in Iceland: A population‐based study

In this study, we determine the incidence and outcomes of Guillain‐Barré syndrome (GBS) in Iceland over a 20‐year period.