| 1. |
- Goodman, Matthew O., et al.
(författare)
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Causal Association Between Subtypes of Excessive Daytime Sleepiness and Risk of Cardiovascular Diseases
- 2023
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 12:24
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Excessive daytime sleepiness (EDS), experienced in 10% to 20% of the population, has been associated with cardiovascular disease and death. However, the condition is heterogeneous and is prevalent in individuals having short and long sleep duration. We sought to clarify the relationship between sleep duration subtypes of EDS with cardiovascular outcomes, accounting for these subtypes. METHODS AND RESULTS: We defined 3 sleep duration subtypes of excessive daytime sleepiness: normal (6-9hours), short (<6hours), and long (>9hours), and compared these with a nonsleepy, normal-sleep-duration reference group. We analyzed their associations with incident myocardial infarction (MI) and stroke using medical records of 355901 UK Biobank participants and performed 2-sample Mendelian randomization for each outcome. Compared with healthy sleep, long-sleep EDS was associated with an 83% increased rate of MI (hazard ratio, 1.83 [95% CI, 1.21-2.77]) during 8.2-year median follow-up, adjusting for multiple health and sociodemographic factors. Mendelian randomization analysis provided supporting evidence of a causal role for a genetic long-sleep EDS subtype in MI (inverse-variance weighted β=1.995, P=0.001). In contrast, we did not find evidence that other subtypes of EDS were associated with incident MI or any associations with stroke (P>0.05). CONCLUSIONS: Our study suggests the previous evidence linking EDS with increased cardiovascular disease risk may be primarily driven by the effect of its long-sleep subtype on higher risk of MI. Underlying mechanisms remain to be investigated but may involve sleep irregularity and circadian disruption, suggesting a need for novel interventions in this population.
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| 2. |
- Ishigaki, Kazuyoshi, et al.
(författare)
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Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:11, s. 1640-1651
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10−8), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.
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| 3. |
- Lagou, Vasiliki, et al.
(författare)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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| 4. |
- Ollila, Hanna M., et al.
(författare)
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Nightmares share genetic risk factors with sleep and psychiatric traits
- 2024
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Nightmares are vivid, extended, and emotionally negative or negative dreams that awaken the dreamer. While sporadic nightmares and bad dreams are common and generally harmless, frequent nightmares often reflect underlying pathologies of emotional regulation. Indeed, insomnia, depression, anxiety, or alcohol use have been associated with nightmares in epidemiological and clinical studies. However, the connection between nightmares and their comorbidities are poorly understood. Our goal was to examine the genetic risk factors for nightmares and estimate correlation or causality between nightmares and comorbidities. We performed a genome-wide association study (GWAS) in 45,255 individuals using a questionnaire-based assessment on the frequency of nightmares during the past month and genome-wide genotyping data. While the GWAS did not reveal individual risk variants, heritability was estimated at 5%. In addition, the genetic correlation analysis showed a robust correlation (rg > 0.4) of nightmares with anxiety (rg = 0.671, p = 7.507e−06), depressive (rg = 0.562, p = 1.282e−07) and posttraumatic stress disorders (rg = 0.4083, p = 0.0152), and personality trait neuroticism (rg = 0.667, p = 4.516e−07). Furthermore, Mendelian randomization suggested causality from insomnia to nightmares (beta = 0.027, p = 0.0002). Our findings suggest that nightmares share genetic background with psychiatric traits and that insomnia may increase an individual’s liability to experience frequent nightmares. Given the significant correlations with psychiatric and psychological traits, it is essential to grow awareness of how nightmares affect health and disease and systematically collect information about nightmares, especially from clinical samples and larger cohorts.
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