| 1. |
- Abdellaoui, A, et al.
(författare)
-
Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness
- 2019
-
Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 28:22, s. 3853-3865
-
Tidskriftsartikel (refereegranskat)abstract
- Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. Although the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. Although it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition toward loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we extended the genome-wide association study meta-analysis of loneliness to 511 280 subjects, and detect 19 significant genetic variants from 16 loci, including four novel loci, as well as 58 significantly associated genes. We investigated the genetic overlap with a wide range of physical and mental health traits by computing genetic correlations and by building loneliness polygenic scores in an independent sample of 18 498 individuals with EHR data to conduct a PheWAS with. A genetic predisposition toward loneliness was associated with cardiovascular, psychiatric, and metabolic disorders and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, the effect of both BMI and body fat on loneliness. Our results provide a framework for future studies of the genetic basis of loneliness and its relationship to mental and physical health.
|
|
| 2. |
- Niederdöckl, Jan, et al.
(författare)
-
The ABC-Stroke Score Refines Stroke Risk Stratification in Patients With Atrial Fibrillation at the Emergency Department
- 2022
-
Ingår i: Frontiers in Medicine. - : Frontiers Media S.A.. - 2296-858X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To evaluate the performance of the ABC (Age, Biomarkers, Clinical history) and CHA(2)DS(2)-VASc stroke scores under real-world conditions in an emergency setting.Methods and Results: The performance of the biomarker-based ABC-stroke score and the clinical variable-based CHA(2)DS(2)-VASc score for stroke risk assessment were prospectively evaluated in a consecutive series of 2,108 patients with acute symptomatic atrial fibrillation at a tertiary care emergency department. Performance was assessed according to methods for the development and validation of clinical prediction models by Steyerberg et al. and the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis. During a cumulative observation period of 3,686 person-years, the stroke incidence rate was 1.66 per 100 person-years. Overall, the ABC-stroke and CHA(2)DS(2)-VASc scores revealed respective c-indices of 0.64 and 0.55 for stroke prediction. Risk-class hazard ratios comparing moderate to low and high to low were 3.51 and 2.56 for the ABC-stroke score and 1.10 and 1.62 for the CHA(2)DS(2)-VASc score. The ABC-stroke score also provided improved risk stratification in patients with moderate stroke risk according to the CHA(2)DS(2)-VASc score, who lack clear recommendations regarding anticoagulation therapy (HR: 4.35, P = 0.001). Decision curve analysis indicated a superior net clinical benefit of using the ABC-stroke score.Conclusion: In a large, real-world cohort of patients with acute atrial fibrillation in the emergency department, the ABC-stroke score was superior to the guideline-recommended CHA(2)DS(2)-VASc score at predicting stroke risk and refined risk stratification of patients labeled moderate risk by the CHA(2)DS(2)-VASc score, potentially easing treatment decision-making.
|
|
