| 1. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 2. |
- Stemann Larsen, Pernille, et al.
(författare)
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Pregnancy and Birth Cohort Resources in Europe: a Large Opportunity for Aetiological Child Health Research
- 2013
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Ingår i: Paediatric and Perinatal Epidemiology. - : Wiley-Blackwell. - 0269-5022 .- 1365-3016. ; 27:4, s. 393-414
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Forskningsöversikt (refereegranskat)abstract
- Background During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. Methods European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. Results In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. Conclusion This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.
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| 3. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 4. |
- Eriksen, Anne Kirstine, et al.
(författare)
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A lifestyle intervention among elderly men on active surveillance for non-aggressive prostate cancer: a randomised feasibility study with whole-grain rye and exercise.
- 2017
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215 .- 1745-6215. ; 18:1, s. 20-
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Tidskriftsartikel (refereegranskat)abstract
- The prognosis for men with non-aggressive prostate cancer is good, and several studies have investigated the impact of lifestyle changes including physical activity and diet on the prognosis. Despite positive results in animal studies and a few human interventions with whole-grain rye on markers of prostate cancer progression, the feasibility of trials investigating such dietary changes in combination with physical activity remains largely unstudied. The primary aim was to investigate the feasibility of an intervention with high whole-grain rye intake and vigorous physical activity for 6 months in men diagnosed with prostate cancer.
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| 5. |
- Garde, Anne Helene, et al.
(författare)
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How to schedule night shift work in order to reduce health and safety risks
- 2020
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 46:6, s. 557-569
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This discussion paper aims to provide scientifically based recommendations on night shift schedules, including consecutive shifts, shift intervals and duration of shifts, which may reduce health and safety risks. Short-term physiological effects in terms of circadian disruption, inadequate sleep duration and quality, and fatigue were considered as possible links between night shift work and selected health and safety risks, namely, cancer, cardio-metabolic disease, injuries, and pregnancy-related outcomes.Method In early 2020, 15 experienced shift work researchers participated in a workshop where they identified relevant scientific literature within their main research area.Results Knowledge gaps and possible recommendations were discussed based on the current evidence. The consensus was that schedules which reduce circadian disruption may reduce cancer risk, particularly for breast cancer, and schedules that optimize sleep and reduce fatigue may reduce the occurrence of injuries. This is generally achieved with fewer consecutive night shifts, sufficient shift intervals, and shorter night shift duration.Conclusions Based on the limited, existing literature, we recommend that in order to reduce the risk of injuries and possibly breast cancer, night shift schedules have: (i) ≤3 consecutive night shifts; (ii) shift intervals of ≥11 hours; and (iii) ≤9 hours shift duration. In special cases – eg, oil rigs and other isolated workplaces with better possibilities to adapt to daytime sleep – additional or other recommendations may apply. Finally, to reduce risk of miscarriage, pregnant women should not work more than one night shift in a week.
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| 8. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 9. |
- Larsen, Anne, et al.
(författare)
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Complex caring needs without simple solutions : the experience of interprofessional collaboration among staff caring for older persons with multimorbidity at home care settings
- 2017
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Ingår i: Scandinavian Journal of Caring Sciences. - 0283-9318 .- 1471-6712. ; 31:2, s. 342-350
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Tidskriftsartikel (refereegranskat)abstract
- Background: Older persons with multimorbidity being cared for at home often have complex needs which can´t be met by one player. Interprofessional collaboration is therefore considered necessary if care is to be organised according to the needs of the elderly. To achieve coherent healthcare, municipalities and regions need to develop this area.Aim: The aim of the study was to illustrate how various professionals belonging to homemaker services, home care services in municipality and Hospital-Based Home Care Services experience their collaboration in caring for older persons with multimorbidity.Method: Eleven informants took part in the study and individual interviewed. The material was analysed using a hermeneutic data analysis.Result: The result shows that collaboration between players contains various types of experiences which influence not only the staff who are involved in collaboration but also the result of the collaboration itself. The informants´ experience of collaboration was defined by trust and distrust and by security and insecurity. These influenced both the staff who were involved in collaboration and the result of collaboration itself.Conlusion: Complex situations could not be solved with simple models. Instead a flexible approach appears necessary with focus shifted from structures to interpersonal relations and interactions. Therefor the different professions have to work as a transprofessional team where close interactions, flexibility and improvisation is a key to success. Relevance to clinical practice: A transprofessional approach to teamwork collaboration can blur professional boundaries and take the competence of all staff into account when home health care to older people with multimorbidity is to be provided by multiple caregivers. This is suggested as an approach with potential to provide high quality and safe care to a vulnerable population.
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| 10. |
- Larsen, Sandra, et al.
(författare)
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Placental weight and birthweight : the relations with number of daily cigarettes and smoking cessation in pregnancy. A population study
- 2018
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Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 47:4, s. 1141-1150
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Tidskriftsartikel (refereegranskat)abstract
- Background: We studied associations of number of daily cigarettes in the first trimester with placental weight and birthweight in women who smoked throughout pregnancy, and in women who stopped smoking after the first trimester. Methods: We included all women with delivery of a singleton in Norway (n = 698 891) during 1999-2014, by using data from the Medical Birth Registry of Norway. We assessed dose-response associations by applying linear regression with restricted cubic splines. Results: In total, 12.6% smoked daily in the first trimester, and 3.7% stopped daily smoking. In women who smoked throughout pregnancy, placental weight and birthweight decreased by number of cigarettes; however, above 11-12 cigarettes we estimated no further decrease (Pnon-linearity < 0.001). Maximum decrease in placental weight in smokers compared with non-smokers was 18.2 g [ 95% confidence interval (CI): 16.6 to 19.7], and for birthweight the maximum decrease was 261.9 g (95% CI: 256.1 to 267.7). In women who stopped smoking, placental weight was higher than in non-smokers and increased by number of cigarettes to a maximum of 16.2 g (95% CI: 9.9 to 22.6). Birthweight was similar in women who stopped smoking and non-smokers, and we found no change by number of cigarettes (Pnon-linearity < 0.001). Conclusions: In women who smoked throughout pregnancy, placental weight and birthweight decreased non-linearly by number of cigarettes in the first trimester. In women who stopped smoking, placental weight was higher than in non-smokers and increased linearly by number of cigarettes; birthweight was almost similar to that of non-smokers.
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