| 1. |
- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 2. |
- Tabassum, R, et al.
(författare)
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Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
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Tidskriftsartikel (refereegranskat)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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| 3. |
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| 4. |
- Kurki, MI, et al.
(författare)
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FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
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Tidskriftsartikel (refereegranskat)abstract
- Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
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| 5. |
- Cuerda, C., et al.
(författare)
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Original article Nutrition education in medical schools (NEMS) project: Joining ESPEN and university point of view
- 2021
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614. ; 40:5, s. 2754-2761
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Nutrition education is not well represented in the medical curriculum. The aim of this original paper was to describe the Nutrition Education in Medical Schools (NEMS) Project of the European Society for Clinical Nutrition and Metabolism (ESPEN). Methods: On 19 January 2020, a meeting was held on this topic that was attended by 51 delegates (27 council members) from 34 countries, and 13 European University representatives. Results: This article includes the contents of the meeting that concluded with the signing of the Manifesto for the Implementation of Nutrition Education in the Undergraduate Medical Curriculum. Conclusion: The meeting represented a significant step forward, moved towards implementation of nutrition education in medical education in general and in clinical practice in particular, in compliance with the aims of the ESPEN Nutrition Education Study Group (NESG). 0 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
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| 6. |
- Pegelow, M., et al.
(författare)
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Reliability and Predictive Validity of Dental Arch Relationships Using the 5-Year-Olds’ Index and the GOSLON Yardstick to Determine Facial Growth
- 2021
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Ingår i: Cleft Palate-Craniofacial Journal. - : SAGE Publications. - 1055-6656 .- 1545-1569. ; 58:5, s. 619-627
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To determine reliability and predictive validity of the 5-year-olds’(5YO) Index and GOSLON Yardstick in 119 patients born with unilateral cleft lip and palate at 5, 7/8, 10, 15/16, and 19 years. Methods: Five hundred thirty-four dental study models were appraised by 2 teams in 2 centers, twice in each center. Intrateam and interteam reliability in scoring the models was calculated using κ. Dental arch prediction rates were calculated as the proportion of models remaining in the same category (good–scores 1 and 2; fair–score 3; poor–scores 4 and 5) over time. Results: Intrateam and interteam κ statistics ranged from 0.74 to 0.89 and from 0.74 to 0.81, respectively. The 5YO Index and GOSLON Yardstick at 5 years produced almost identical results. The prediction rate of 19-year-old (n = 106) outcome was >80% for those in groups 1 and 2 at 5 years, while for those in groups 4 and 5 prediction was poor (<40%). Prediction of groups 4 and 5 remained poor until 10 years when it increased to 77%. At 15/16 years prediction rate was 93% for those in groups 4 and 5. Prediction of cases in group 3 was very poor at all ages. Conclusions: These results question the predictive value of “poor” dental arch relationships before 10 years of age. However, the predictive value of “good” dental arch relationship scores over time is good in all age groups. This has implications for audit policies to predict facial growth outcomes. © American Cleft Palate-Craniofacial Association. All rights reserved 2020.
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| 7. |
- Saarentaus, EC, et al.
(författare)
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Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation
- 2023
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 83-
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory and infectious upper respiratory diseases (ICD-10: J30-J39), such as diseases of the sinonasal tract, pharynx and larynx, are growing health problems yet their genomic similarity is not known. We analyze genome-wide association to eight upper respiratory diseases (61,195 cases) among 260,405 FinnGen participants, meta-analyzing diseases in four groups based on an underlying genetic correlation structure. Aiming to understand which genetic loci contribute to susceptibility to upper respiratory diseases in general and its subtypes, we detect 41 independent genome-wide significant loci, distinguishing impact on sinonasal or pharyngeal diseases, or both. Fine-mapping implicated non-synonymous variants in nine genes, including three linked to immune-related diseases. Phenome-wide analysis implicated asthma and atopic dermatitis at sinonasal disease loci, and inflammatory bowel diseases and other immune-mediated disorders at pharyngeal disease loci. Upper respiratory diseases also genetically correlated with autoimmune diseases such as rheumatoid arthritis, autoimmune hypothyroidism, and psoriasis. Finally, we associated separate gene pathways in sinonasal and pharyngeal diseases that both contribute to type 2 immunological reaction. We show shared heritability among upper respiratory diseases that extends to several immune-mediated diseases with diverse mechanisms, such as type 2 high inflammation.
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| 8. |
- Saarentaus, EC, et al.
(författare)
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Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation
- 2023
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 83-
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory and infectious upper respiratory diseases (ICD-10: J30-J39), such as diseases of the sinonasal tract, pharynx and larynx, are growing health problems yet their genomic similarity is not known. We analyze genome-wide association to eight upper respiratory diseases (61,195 cases) among 260,405 FinnGen participants, meta-analyzing diseases in four groups based on an underlying genetic correlation structure. Aiming to understand which genetic loci contribute to susceptibility to upper respiratory diseases in general and its subtypes, we detect 41 independent genome-wide significant loci, distinguishing impact on sinonasal or pharyngeal diseases, or both. Fine-mapping implicated non-synonymous variants in nine genes, including three linked to immune-related diseases. Phenome-wide analysis implicated asthma and atopic dermatitis at sinonasal disease loci, and inflammatory bowel diseases and other immune-mediated disorders at pharyngeal disease loci. Upper respiratory diseases also genetically correlated with autoimmune diseases such as rheumatoid arthritis, autoimmune hypothyroidism, and psoriasis. Finally, we associated separate gene pathways in sinonasal and pharyngeal diseases that both contribute to type 2 immunological reaction. We show shared heritability among upper respiratory diseases that extends to several immune-mediated diseases with diverse mechanisms, such as type 2 high inflammation.
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