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- Hautakangas, H, et al.
(författare)
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Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:2, s. 152-
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Tidskriftsartikel (refereegranskat)abstract
- Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
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| 2. |
- Johnsen, SE, et al.
(författare)
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Encoding of amplitude and rate of tooth loads by human periodontal afferents from premolar and molar teeth
- 2005
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 93:4, s. 1889-1897
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Tidskriftsartikel (refereegranskat)abstract
- Microneurographic recordings were obtained from 20 periodontal mechanoreceptive afferents in the inferior alveolar nerve while force profiles of different amplitudes and rates were applied to a premolar or the first molar in the most sensitive direction. The majority of afferents (17/20) showed a hyperbolic relationship between the steady-state discharge rate and the amplitude of the stimulating force, featuring a pronounced saturation tendency. These afferents were also characterized by a similar decline in dynamic sensitivity with increasing amplitude of background force. However, a few afferents (3/20) showed nearly linear stimulus-response relationships and a small decline in dynamic sensitivity with increasing tooth load. Quantitative models developed for all afferents successfully predicted the afferent discharge rates for novel force stimulations. Application of the transfer function to chewing forces predicted that the discharge rates of periodontal afferents rapidly increased at initial tooth contact and continued to discharge as long as the tooth was loaded. However, due to the marked saturation tendencies at higher forces, most periodontal afferents poorly encoded the magnitude of the strong chewing forces. In addition, the discharge rates of a minority of afferents continued to reflect the force profile during high chewing forces. The results revealed that periodontal afferents of posterior teeth were less sensitive at low tooth loads compared with afferents of anterior teeth. During each chewing cycle, periodontal afferents may provide information about the mechanical properties of food shortly after tooth contact that can be used to scale the muscle commands of the upcoming power phase.
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| 5. |
- Johnsen, SE, et al.
(författare)
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Receptive field properties of human periodontal afferents responding to loading of premolar and molar teeth
- 2003
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 89:3, s. 1478-1487
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Tidskriftsartikel (refereegranskat)abstract
- Impulses in 45 single mechanoreceptive afferents were recorded from the human inferior alveolar nerve with permucosally inserted tungsten microelectrodes. All afferents responded to mechanical stimulation of one or more premolar or molar teeth and most likely innervated their periodontal ligaments. For each afferent, isolated “ramp-and-hold” shaped force profiles of similar magnitudes (252 ± 24 mN; mean ± SD) were applied to the lower first premolar, the second premolar, and the first molar on the recording side. The tooth loads were applied in six directions: lingual, facial, mesial, and distal in the horizontal plane and up and down in the vertical direction of the tooth. The afferents response during the static phase of the stimulus was analyzed. All afferents were slowly adapting, discharging continuously in response to static forces in at least one stimulation direction. Twenty-nine afferents (64%) were spontaneously active, exhibiting an ongoing discharge in the absence of external stimulation. Stimulation of a single tooth was found to excite each afferent most strongly. The most sensitive tooth (MST) was the first premolar for 23, the second premolar for 13, and the first molar for 9 afferents. About half of the afferent population also responded to loading of one or two more teeth. The response profiles of these afferents indicated that the multiple-teeth receptive fields were due to mechanical coupling between the teeth rather than branching of single afferents to innervate several teeth. The afferent responses to loading the mesial and distal halves of the first molars were very similar. Thus both intensive and directional aspects of the afferent response when loading one side of the tooth was preserved to a great extent when loading the other side. When loading the MST, the afferents typically showed excitatory responses in two to four of the six stimulation directions, i.e., the afferents were broadly tuned to direction of tooth loading. In the horizontal plane, the afferent populations at the premolar teeth expressed no clear directional preferences. The afferents at the molar, however, showed a strong directional bias in the distal-lingual direction. In the vertical plane, there was a preference for downward-directed forces with a gradually decreasing sensitivity distally along the dental arch. The present results demonstrate that human periodontal afferents supplying anterior and posterior teeth differ in their capacity to signal horizontal and vertical forces, respectively.
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