| 1. |
- Bakker, M. K., et al.
(författare)
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Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:12, s. 1303-1313
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Tidskriftsartikel (refereegranskat)abstract
- Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits. Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.
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| 2. |
- Lassmann-Klee, P. G., et al.
(författare)
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Parallel gradients in F-ENO and in the prevalences of asthma and atopy in adult general populations of Sweden, Finland and Estonia - A Nordic EpiLung study
- 2020
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 173
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of asthma is higher in Sweden and Finland than in neighbouring eastern countries including Estonia. Corresponding difference in bronchial eosinophilic inflammation could be studied by FENO measurements. We aimed to compare FENO in adult general populations of Sweden, Finland, and Estonia, to test the plausibility of the west-east disparity hypothesis of allergic diseases. We conducted clinical interviews (N = 2658) with participants randomly selected from the general populations in Sweden (Stockholm and dOrebro), Finland (Helsinki), and Estonia (Narva and Saaremaa), and performed FENO (n = 1498) and skin prick tests (SPT) in 1997-2003. The median (interquartile range) of FENO (ppb) was 15.5 (9.3) in Sweden, 15.4 (13.6) in Finland and 12.5 (9.6) in Estonia. We found the lowest median FENO values in the Estonian centres Saaremaa 13.1 (9.5) and Narva 11.8 (8.6). In the pooled population, asthma was associated with FENO >= 25 ppb, odds ratio (OR) 3.91 (95% confidence intervals: 2.29-6.32) after adjusting for SPT result, smoking, gender and study centre. A positive SPT test increased the likelihood of asthma OR 3.19 (2.02-5.11). Compared to Saaremaa, the likelihood of having asthma was higher in Helsinki OR 2.40 (1.04-6.02), Narva OR 2.45 (1.05-6.19), dOrebro OR 3.38 (1.59-8.09), and Stockholm OR 5.54 (2.18-14.79). There was a higher prevalence of asthma and allergic airway inflammation in adult general populations of Sweden and Finland compared to those of Estonia. Atopy and elevated FEND level were independently associated with an increased risk of asthma. In conclusion, the findings support the earlier west-east disparity hypothesis of allergic diseases.
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| 3. |
- Brumpton, B, et al.
(författare)
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Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3519-
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Tidskriftsartikel (refereegranskat)abstract
- Estimates from Mendelian randomization studies of unrelated individuals can be biased due to uncontrolled confounding from familial effects. Here we describe methods for within-family Mendelian randomization analyses and use simulation studies to show that family-based analyses can reduce such biases. We illustrate empirically how familial effects can affect estimates using data from 61,008 siblings from the Nord-Trøndelag Health Study and UK Biobank and replicated our findings using 222,368 siblings from 23andMe. Both Mendelian randomization estimates using unrelated individuals and within family methods reproduced established effects of lower BMI reducing risk of diabetes and high blood pressure. However, while Mendelian randomization estimates from samples of unrelated individuals suggested that taller height and lower BMI increase educational attainment, these effects were strongly attenuated in within-family Mendelian randomization analyses. Our findings indicate the necessity of controlling for population structure and familial effects in Mendelian randomization studies.
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| 4. |
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| 5. |
- Vikjord, S. A. A., et al.
(författare)
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The association of anxiety and depression with mortality in a COPD cohort. The HUNT study, Norway
- 2020
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111. ; 171
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Tidskriftsartikel (refereegranskat)abstract
- Background: Anxiety and depression are prevalent among individuals with chronic obstructive pulmonary disease (COPD), but the impact of these comorbidities on long-term mortality is unknown. Aims: This study aims to compare mortality in individuals with COPD who had or did not have symptoms of anxiety or depression as well as the impact of a change in these symptoms on mortality. Methods: Individuals with COPD according to the Global Lung Initiative (GLI) LLN criteria (n = 2076) were recruited from the second (1995-97) and third (2006-08) surveys of the HUNT Study and followed until January 2019 for mortality. We assessed baseline status of anxiety or depression using the Hospital Anxiety and Depression Scale (HADS), and probable cases were defined by a score >= 8. We used Cox regression to calculate hazard ratios (HR) with 95% confidence intervals (CI). Change in HADS score over time was assessed using joint models. Results: Among the individuals with COPD, 16.2% had symptoms of anxiety and 15.9% had symptoms of depression. Compared to those with HADS-A and -D score <8, symptoms of anxiety or depression increased mortality by 21% (95% CI 05-47%) and 21% (2-44%), respectively. Over the approximately 11-year period between surveys, change of HADS-A from >= 8 to <8 was associated with a decrease in mortality (HR 0.97 [95% CI 0.94-1.00]), but not in HADS-D (0.97 [95% CI 0.93-1.18]). Conclusions: Individuals with COPD and symptoms of anxiety or depression have increased mortality, and improved HADS-A score with time is associated with lower mortality.
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