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- Emilsson, Össur Ingi, et al.
(författare)
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Snoring and nocturnal reflux : association with lung function decline and respiratory symptoms
- 2019
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Ingår i: ERJ Open Research. - : European Respitory Society (ERS). - 2312-0541. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The study aim was to examine the association of snoring and nocturnal gastro-oesophageal reflux (nGOR) with respiratory symptoms and lung function, and if snoring and/or nGOR associated with a steeper decline in lung function. Methods: Data from the third visit of the European Community Respiratory Health Survey (ECRHS) was used for cross-sectional analysis. Pre- and post-bronchodilator spirometry was performed, and information on sleep, nGOR and respiratory symptoms was collected (n=5715). Habitual snoring and nGOR were assessed by questionnaire reports. Pre-bronchodilator spirometry from ECRHS I, II and III (20 years follow-up) were used to analyse lung function changes by multivariate regression analysis. Results: Snoring and nGOR were independently associated with a higher prevalence of wheeze, chest tightness, breathlessness, cough and phlegm. The prevalence of any respiratory symptom was 79% in subjects with both snoring and nGOR versus 56% in those with neither (p<0.001). Subjects with both snoring and nGOR had more frequent exacerbations (adjusted prevalence 32% versus 19% among "no snoring, no nGOR", p=0.003). Snoring but not nGOR was associated with a steeper decline in forced expiratory volume in 1 s over 10 years after adjusting for confounding factors (change in % predicted -5.53, versus -4.58 among "no snoring", p=0.04) and forced vital capacity (change in % predicted -1.94, versus -0.99 among "no snoring", p=0.03). Conclusions: Adults reporting both habitual snoring and nGOR had more respiratory symptoms and more frequent exacerbations of these symptoms. Habitual snoring was associated with a steeper decline in lung function over time.
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| 2. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 3. |
- Jakobsdottir, Johanna, et al.
(författare)
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Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease
- 2016
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (similar to 0.5% versus < 0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES substudy, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5-15.9), p = 6.6x10(-9)]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the beta-amyloid cascade.
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