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- Skuladottir, AT, et al.
(författare)
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A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1598-
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Tidskriftsartikel (refereegranskat)abstract
- Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and has a largely unknown underlying biology. In a genome-wide association study of CTS (48,843 cases and 1,190,837 controls), we found 53 sequence variants at 50 loci associated with the syndrome. The most significant association is with a missense variant (p.Glu366Lys) in SERPINA1 that protects against CTS (P = 2.9 × 10−24, OR = 0.76). Through various functional analyses, we conclude that at least 22 genes mediate CTS risk and highlight the role of 19 CTS variants in the biology of the extracellular matrix. We show that the genetic component to the risk is higher in bilateral/recurrent/persistent cases than nonrecurrent/nonpersistent cases. Anthropometric traits including height and BMI are genetically correlated with CTS, in addition to early hormonal-replacement therapy, osteoarthritis, and restlessness. Our findings suggest that the components of the extracellular matrix play a key role in the pathogenesis of CTS.
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| 2. |
- 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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| 3. |
- Vogt, E. C., et al.
(författare)
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Premature menopause and autoimmune primary ovarian insufficiency in two international multi-center cohorts
- 2022
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Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate markers of premature menopause (<40 years) and specifically the prevalence of autoimmune primary ovarian insufficiency (POI) in European women. Design: Postmenopausal women were categorized according to age at menopause and self-reported reason for menopause in a cross-sectional analysis of 6870 women. Methods: Variables associated with the timing of menopause and hormone measurements of 17 beta-estradiol and follicle-stimulating hormone were explored using multivariable logistic regression analysis. Specific immunoprecipitating assays of steroidogenic autoantibodies against 21-hydroxylase (21-OH), side-chain cleavage enzyme (anti-SCC) and 17alpha-hydroxylase (17 OH), as well as NACHT leucine-rich-repeat protein 5 were used to identify women with likely autoimmune POI. Results: Premature menopause was identified in 2.8% of women, and these women had higher frequencies of nulliparity (37.4% vs 19.7%), obesity (28.7% vs 21.4%), osteoporosis (17.1% vs 11.6%), hormone replacement therapy (59.1% vs 36.9%) and never smokers (60.1% vs 50.9%) (P < 0.05), compared to women with menopause >= 40 years. Iatrogenic causes were found in 91 (47%) and non-ovarian causes in 27 (14%) women, while 77 (39%) women were classified as POI of unknown cause, resulting in a 1.1% prevalence of idiopathic POI. After adjustments nulliparity was the only variable significantly associated with POI (odds ratio 2.46; 95% CI 1.63-3.42). Based on the presence of autoantibodies against 21 OH and SCC, 4.5% of POI cases were of likely autoimmune origin. Conclusion: Idiopathic POI affects 1.1% of all women and almost half of the women with premature menopause. Autoimmunity explains 4.5% of these cases judged by positive steroidogenic autoantibodies.
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| 7. |
- Gisladottir, Rosa S, et al.
(författare)
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Sequence Variants in TAAR5 and Other Loci Affect Human Odor Perception and Naming.
- 2020
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Ingår i: Current biology : CB. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 30:23
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Tidskriftsartikel (refereegranskat)abstract
- Olfactory receptor (OR) genes in humans form a special class characterized by unusually high DNA sequence diversity, which should give rise to differences in perception and behavior. In the largest genome-wide association study to date based on olfactory testing, we investigated odor perception and naming with smell tasks performed by 9,122 Icelanders, with replication in a separate sample of 2,204 individuals. We discovered an association between a low-frequency missense variant in TAAR5 and reduced intensity rating of fish odor containing trimethylamine (p.Ser95Pro, pcombined= 5.6× 10-15). We demonstrate that TAAR5 genotype affects aversion to fish odor, reflected by linguistic descriptions of the odor and pleasantness ratings. We also discovered common sequence variants in two canonical olfactory receptor loci that associate with increased intensity and naming of licorice odor (trans-anethole: lead variant p.Lys233Asn in OR6C70, pcombined= 8.8× 10-16 and pcombined= 1.4× 10-9) and enhanced naming of cinnamon (trans-cinnamaldehyde; intergenic variant rs317787-T, pcombined= 5.0× 10-17). Together, our results show that TAAR5 genotype variation influences human odor responses and highlight that sequence diversity in canonical OR genes can lead to enhanced olfactory ability, in contrast to the view that greater tolerance for mutations in the human OR repertoire leads to diminished function.
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| 9. |
- Skuladottir, AT, et al.
(författare)
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A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo
- 2021
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1, s. 1148-
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Tidskriftsartikel (refereegranskat)abstract
- Vertigo is the leading symptom of vestibular disorders and a major risk factor for falls. In a genome-wide association study of vertigo (Ncases = 48,072, Ncontrols = 894,541), we uncovered an association with six common sequence variants in individuals of European ancestry, including missense variants in ZNF91, OTOG, OTOGL, and TECTA, and a cis-eQTL for ARMC9. The association of variants in ZNF91, OTOGL, and OTOP1 was driven by an association with benign paroxysmal positional vertigo. Using previous reports of sequence variants associating with age-related hearing impairment and motion sickness, we found eight additional variants that associate with vertigo. Although disorders of the auditory and the vestibular system may co-occur, none of the six genome-wide significant vertigo variants were associated with hearing loss and only one was associated with age-related hearing impairment. Our results uncovered sequence variants associating with vertigo in a genome-wide association study and implicated genes with known roles in inner ear development, maintenance, and disease.
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| 11. |
- Bjornsdottir, E., et al.
(författare)
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Are symptoms of insomnia related to respiratory symptoms? Cross-sectional results from 10 European countries and Australia
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To compare the prevalence of different insomnia subtypes among middle-aged adults from Europe and Australia and to explore the cross-sectional relationship between insomnia subtypes, respiratory symptoms and lung function. Design Cross-sectional population-based, multicentre cohort study. Setting 23 centres in 10 European countries and Australia. Methods We included 5800 participants in the third follow-up of the European Community Respiratory Health Survey III (ECRHS III) who answered three questions on insomnia symptoms: difficulties falling asleep (initial insomnia), waking up often during the night (middle insomnia) and waking up early in the morning and not being able to fall back asleep (late insomnia). They also answered questions on smoking, general health and chronic diseases and had the following lung function measurements: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the FEV1/FVC ratio. Changes in lung function since ECRHS I about 20 years earlier were also analysed. Main outcome measures Prevalence of insomnia subtypes and relationship to respiratory symptoms and function. Results Overall, middle insomnia (31.2%) was the most common subtype followed by late insomnia (14.2%) and initial insomnia (11.2%). The highest reported prevalence of middle insomnia was found in Iceland (37.2%) and the lowest in Australia (22.7%), while the prevalence of initial and late insomnia was highest in Spain (16.0% and 19.7%, respectively) and lowest in Denmark (4.6% and 9.2%, respectively). All subtypes of insomnia were associated with significantly higher reported prevalence of respiratory symptoms. Only isolated initial insomnia was associated with lower FEV1, whereas no association was found between insomnia and low FEV1/FVC ratio or decline in lung function. Conclusion There is considerable geographical variation in the prevalence of insomnia symptoms. Middle insomnia is most common especially in Iceland. Initial and late insomnia are most common in Spain. All insomnia subtypes are associated with respiratory symptoms, and initial insomnia is also associated with lower FEV1.
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| 12. |
- Bjornsdottir, Erla, et al.
(författare)
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Association between physical activity over a 10-year period and current insomnia symptoms, sleep duration and daytime sleepiness : a European population-based study
- 2024
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To explore the relationship between physical activity over a 10-year period and current symptoms of insomnia, daytime sleepiness and estimated sleep duration in adults aged 39-67.DESIGN: Population-based, multicentre cohort study. SETTING: 21 centres in nine European countries.METHODS: Included were 4339 participants in the third follow-up to the European Community Respiratory Health Survey (ECRHS III), who answered questions on physical activity at baseline (ECRHS II) and questions on physical activity, insomnia symptoms, sleep duration and daytime sleepiness at 10-year follow-up (ECRHS III). Participants who reported that they exercised with a frequency of at least two or more times a week, for 1 hour/week or more, were classified as being physically active. Changes in activity status were categorised into four groups: persistently non-active; became inactive; became active; and persistently active.MAIN OUTCOME MEASURES: Insomnia, sleep time and daytime sleepiness in relation to physical activity.RESULTS: Altogether, 37% of participants were persistently non-active, 25% were persistently active, 20% became inactive and 18% became active from baseline to follow-up. Participants who were persistently active were less likely to report difficulties initiating sleep (OR 0.60, 95% CI 0.45-0.78), a short sleep duration of ≤6 hours/night (OR 0.71, 95% CI 0.59-0.85) and a long sleep of ≥9 hours/night (OR 0.53, 95% CI 0.33-0.84) than persistently non-active subjects after adjusting for age, sex, body mass index, smoking history and study centre. Daytime sleepiness and difficulties maintaining sleep were not related to physical activity status.CONCLUSION: Physically active people have a lower risk of some insomnia symptoms and extreme sleep durations, both long and short.
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| 13. |
- Bjornsdottir, Erla, et al.
(författare)
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Association between physical activity over a 10-year period and current insomnia symptoms, sleep duration and daytime sleepiness: a European population-based study
- 2024
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Ingår i: BMJ OPEN. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To explore the relationship between physical activity over a 10-year period and current symptoms of insomnia, daytime sleepiness and estimated sleep duration in adults aged 39-67. Design Population-based, multicentre cohort study. Setting 21 centres in nine European countries. Methods Included were 4339 participants in the third follow-up to the European Community Respiratory Health Survey (ECRHS III), who answered questions on physical activity at baseline (ECRHS II) and questions on physical activity, insomnia symptoms, sleep duration and daytime sleepiness at 10-year follow-up (ECRHS III). Participants who reported that they exercised with a frequency of at least two or more times a week, for 1 hour/week or more, were classified as being physically active. Changes in activity status were categorised into four groups: persistently non-active; became inactive; became active; and persistently active. Main outcome measures Insomnia, sleep time and daytime sleepiness in relation to physical activity. Results Altogether, 37% of participants were persistently non-active, 25% were persistently active, 20% became inactive and 18% became active from baseline to follow-up. Participants who were persistently active were less likely to report difficulties initiating sleep (OR 0.60, 95% CI 0.45-0.78), a short sleep duration of <= 6 hours/night (OR 0.71, 95% CI 0.59-0.85) and a long sleep of >= 9 hours/night (OR 0.53, 95% CI 0.33-0.84) than persistently non-active subjects after adjusting for age, sex, body mass index, smoking history and study centre. Daytime sleepiness and difficulties maintaining sleep were not related to physical activity status. Conclusion Physically active people have a lower risk of some insomnia symptoms and extreme sleep durations, both long and short.
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