| 291. |
- Lona-Durazo, Frida, et al.
(författare)
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Meta-analysis of GWA studies provides new insights on the genetic architecture of skin pigmentation in recently admixed populations
- 2019
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Ingår i: BMC Genetics. - : BMC. - 1471-2156. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- Background: Association studies in recently admixed populations are extremely useful to identify the genetic architecture of pigmentation, due to their high genotypic and phenotypic variation. However, to date only four Genome-Wide Association Studies (GWAS) have been carried out in these populations.Results: We present a GWAS of skin pigmentation in an admixed sample from Cuba (N=762). Additionally, we conducted a meta-analysis including the Cuban sample, and admixed samples from Cape Verde, Puerto Rico and African-Americans from San Francisco. This meta-analysis is one of the largest efforts so far to characterize the genetic basis of skin pigmentation in admixed populations (N=2,104). We identified five genome-wide significant regions in the meta-analysis, and explored if the markers observed in these regions are associated with the expression of relevant pigmentary genes in human melanocyte cultures. In three of the regions identified in the meta-analysis (SLC24A5, SLC45A2, and GRM5/TYR), the association seems to be driven by non-synonymous variants (rs1426654, rs16891982, and rs1042602, respectively). The rs16891982 polymorphism is strongly associated with the expression of the SLC45A2 gene. In the GRM5/TYR region, in addition to the rs1042602 non-synonymous SNP located on the TYR gene, variants located in the nearby GRM5 gene have an independent effect on pigmentation, possibly through regulation of gene expression of the TYR gene. We also replicated an association recently described near the MFSD12 gene on chromosome 19 (lead variant rs112332856). Additionally, our analyses support the presence of multiple signals in the OCA2/HERC2/APBA2 region on chromosome 15. A clear causal candidate is the HERC2 intronic variant rs12913832, which has a profound influence on OCA2 expression. This variant has pleiotropic effects on eye, hair, and skin pigmentation. However, conditional and haplotype-based analyses indicate the presence of other variants with independent effects on melanin levels in OCA2 and APBA2. Finally, a follow-up of genome-wide signals identified in a recent GWAS for tanning response indicates that there is a substantial overlap in the genetic factors influencing skin pigmentation and tanning response.Conclusions: Our meta-analysis of skin pigmentation GWAS in recently admixed populations provides new insights about the genetic architecture of this complex trait.
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| 292. |
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| 293. |
- Lu, Chun-Wei, et al.
(författare)
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Heart Failure and Patient-Reported Outcomes in Adults With Congenital Heart Disease from 15 Countries
- 2022
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Ingår i: Journal of the American Heart Association. - : American Heart Association. - 2047-9980. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure (HF) is the leading cause of mortality and associated with significant morbidity in adults with congenital heart disease. We sought to assess the association between HF and patient-report outcomes in adults with congenital heart disease.Methods and Results: As part of the APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease-International Study), we collected data on HF status and patient-reported outcomes in 3959 patients from 15 countries across 5 continents. Patient-report outcomes were: perceived health status (12-item Short Form Health Survey), quality of life (Linear Analogue Scale and Satisfaction with Life Scale), sense of coherence-13, psychological distress (Hospital Anxiety and Depression Scale), and illness perception (Brief Illness Perception Questionnaire). In this sample, 137 (3.5%) had HF at the time of investigation, 298 (7.5%) had a history of HF, and 3524 (89.0%) had no current or past episode of HF. Patients with current or past HF were older and had a higher prevalence of complex congenital heart disease, arrhythmias, implantable cardioverter-defibrillators, other clinical comorbidities, and mood disorders than those who never had HF. Patients with HF had worse physical functioning, mental functioning, quality of life, satisfaction with life, sense of coherence, depressive symptoms, and illness perception scores. Magnitudes of differences were large for physical functioning and illness perception and moderate for mental functioning, quality of life, and depressive symptoms.Conclusions: HF in adults with congenital heart disease is associated with poorer patient-reported outcomes, with large effect sizes for physical functioning and illness perception.
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| 294. |
- Löfgren, Sara E, et al.
(författare)
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Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene
- 2012
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 13:3, s. 268-274
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Tidskriftsartikel (refereegranskat)abstract
- A recent genome-wide association study revealed a variant (rs2431697) in an intergenic region, between the pituitary tumor-transforming 1 (PTTG1) and microRNA (miR-146a) genes, associated with systemic lupus erythematosus (SLE) susceptibility. Here, we analyzed with a case-control design this variant and other candidate polymorphisms in this region together with expression analysis in order to clarify to which gene this association is related. The single-nucleotide polymorphisms (SNPs) rs2431697, rs2910164 and rs2277920 were genotyped by TaqMan assays in 1324 SLE patients and 1453 healthy controls of European ancestry. Genetic association was statistically analyzed using Unphased. Gene expression of PTTG1, the miRNAs miR-3142 and primary and mature forms of miR-146a in peripheral blood mononuclear cells (PBMCs) were assessed by quantitative real-time PCR. Of the three variants analyzed, only rs2431697 was genetically associated with SLE in Europeans. Gene expression analysis revealed that this SNP was not associated with PTTG1 expression levels, but with the microRNA-146a, where the risk allele correlates with lower expression of the miRNA. We replicated the genetic association of rs2341697 with SLE in a case-control study in Europeans and demonstrated that the risk allele of this SNP correlates with a downregulation of the miRNA 146a, potentially important in SLE etiology.
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| 295. |
- Mackenbach, J. P., et al.
(författare)
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Variations in the relation between education and cause-specific mortality in 19 European populations : A test of the "fundamental causes" theory of social inequalities in health
- 2015
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Ingår i: Social Science and Medicine. - : Elsevier BV. - 0277-9536 .- 1873-5347. ; 127, s. 51-62
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Tidskriftsartikel (refereegranskat)abstract
- Link and Phelan have proposed to explain the persistence of health inequalities from the fact that socioeconomic status is a "fundamental cause" which embodies an array of resources that can be used to avoid disease risks no matter what mechanisms are relevant at any given time. To test this theory we compared the magnitude of inequalities in mortality between more and less preventable causes of death in 19 European populations, and assessed whether inequalities in mortality from preventable causes are larger in countries with larger resource inequalities.We collected and harmonized mortality data by educational level on 19 national and regional populations from 16 European countries in the first decade of the 21st century. We calculated age-adjusted Relative Risks of mortality among men and women aged 30-79 for 24 causes of death, which were classified into four groups: amenable to behavior change, amenable to medical intervention, amenable to injury prevention, and non-preventable.Although an overwhelming majority of Relative Risks indicate higher mortality risks among the lower educated, the strength of the education-mortality relation is highly variable between causes of death and populations. Inequalities in mortality are generally larger for causes amenable to behavior change, medical intervention and injury prevention than for non-preventable causes. The contrast between preventable and non-preventable causes is large for causes amenable to behavior change, but absent for causes amenable to injury prevention among women. The contrast between preventable and non-preventable causes is larger in Central & Eastern Europe, where resource inequalities are substantial, than in the Nordic countries and continental Europe, where resource inequalities are relatively small, but they are absent or small in Southern Europe, where resource inequalities are also large.In conclusion, our results provide some further support for the theory of "fundamental causes". However, the absence of larger inequalities for preventable causes in Southern Europe and for injury mortality among women indicate that further empirical and theoretical analysis is necessary to understand when and why the additional resources that a higher socioeconomic status provides, do and do not protect against prevailing health risks.
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| 296. |
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| 297. |
- Major, B., et al.
(författare)
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Macroscopic Optimization of High Harmonic Generation for High Power Laser Pulses
- 2016
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Ingår i: High Intensity Lasers and High Field Phenomena, HILAS 2016. - 9781943580095 ; Part F15-HILAS 2016
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Konferensbidrag (refereegranskat)abstract
- We study upscaling of gas high harmonic generation, to make efficient use of the ever increasing laser pulse powers. Loose focusing geometries optimizing phasematching are investigated and compared in HHG efficiency to shorter focusing arrangements.
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| 298. |
- Maróti, Zoltán, et al.
(författare)
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The genetic origin of Huns, Avars, and conquering Hungarians
- 2022
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:13, s. 2858-2870, 2858–2870.e1–e7
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Tidskriftsartikel (refereegranskat)abstract
- Huns, Avars, and conquering Hungarians were migration-period nomadic tribal confederations that arrived in three successive waves in the Carpathian Basin between the 5th and 9th centuries. Based on the historical data, each of these groups are thought to have arrived from Asia, although their exact origin and relation to other ancient and modern populations have been debated. Recently, hundreds of ancient genomes were analyzed from Central Asia, Mongolia, and China, from which we aimed to identify putative source populations for the above-mentioned groups. In this study, we have sequenced 9 Hun, 143 Avar, and 113 Hungarian conquest period samples and identified three core populations, representing immigrants from each period with no recent European ancestry. Our results reveal that this “immigrant core” of both Huns and Avars likely originated in present day Mongolia, and their origin can be traced back to Xiongnus (Asian Huns), as suggested by several historians. On the other hand, the “immigrant core” of the conquering Hungarians derived from an earlier admixture of Mansis, early Sarmatians, and descendants of late Xiongnus. We have also shown that a common “proto-Ugric” gene pool appeared in the Bronze Age from the admixture of Mezhovskaya and Nganasan people, supporting genetic and linguistic data. In addition, we detected shared Hun-related ancestry in numerous Avar and Hungarian conquest period genetic outliers, indicating a genetic link between these successive nomadic groups. Aside from the immigrant core groups, we identified that the majority of the individuals from each period were local residents harboring “native European” ancestry.
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| 299. |
- Martel-Duguech, Luciana Maria, et al.
(författare)
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ESE audit on management of Adult Growth Hormone Deficiency in clinical practice.
- 2021
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Ingår i: European journal of endocrinology. - 1479-683X. ; 184:2, s. 323-334
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Tidskriftsartikel (refereegranskat)abstract
- Guidelines recommend adults with pituitary disease in whom GH therapy is contemplated, to be tested for GH deficiency (AGHD); however, clinical practice is not uniform.1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD.On-line survey in endocrine centres throughout Europe.Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018.Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved.Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.
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| 300. |
- Massier, L, et al.
(författare)
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Impaired Intestinal Barrier and Tissue Bacteria: Pathomechanisms for Metabolic Diseases
- 2021
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Ingår i: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 12, s. 616506-
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Tidskriftsartikel (refereegranskat)abstract
- An intact intestinal barrier, representing the interface between inner and outer environments, is an integral regulator of health. Among several factors, bacteria and their products have been evidenced to contribute to gut barrier impairment and its increased permeability. Alterations of tight junction integrity - caused by both external factors and host metabolic state - are important for gut barrier, since they can lead to increased influx of bacteria or bacterial components (endotoxin, bacterial DNA, metabolites) into the host circulation. Increased systemic levels of bacterial endotoxins and DNA have been associated with an impaired metabolic host status, manifested in obesity, insulin resistance, and associated cardiovascular complications. Bacterial components and cells are distributed to peripheral tissues via the blood stream, possibly contributing to metabolic diseases by increasing chronic pro-inflammatory signals at both tissue and systemic levels. This response is, along with other yet unknown mechanisms, mediated by toll like receptor (TLR) transduction and increased expression of pro-inflammatory cytokines, which in turn can further increase intestinal permeability leading to a detrimental positive feedback loop. The modulation of gut barrier function through nutritional and other interventions, including manipulation of gut microbiota, may represent a potential prevention and treatment target for metabolic diseases.
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