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5. Whole-Exome Sequencing of 2,000 Danish Individuals and the Role of Rare Coding Variants in Type 2 Diabetes

Author

Lohmueller, Kirk E, Sparsø, Thomas, Li, Qibin, Andersson, Ehm, Korneliussen, Thorfinn, Albrechtsen, Anders, Banasik, Karina, Grarup, Niels, Hallgrimsdottir, Ingileif, Kiil, Kristoffer, Kilpeläinen, Tuomas O, Krarup, Nikolaj T, Pers, Tune H, Sanchez, Gaston, Hu, Youna, DeGiorgio, Michael, Jørgensen, Torben, Sandbæk, Annelli, Lauritzen, Torsten, Brunak, Søren, Kristiansen, Karsten, Li, Yingrui, Hansen, Torben, Wang, Jun, Nielsen, Rasmus, and Pedersen, Oluf

Subjects
Biological Sciences, Genetics, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Published
2014

7. Whole-exome sequencing of 2,000 Danish individuals and the role of rare coding variants in type 2 diabetes.

Author

Lohmueller, Kirk, Sparsø, Thomas, Li, Qibin, Andersson, Ehm, Korneliussen, Thorfinn, Albrechtsen, Anders, Banasik, Karina, Grarup, Niels, Hallgrimsdottir, Ingileif, Kiil, Kristoffer, Kilpeläinen, Tuomas, Krarup, Nikolaj, Pers, Tune, Sanchez, Gaston, Hu, Youna, Degiorgio, Michael, Jørgensen, Torben, Sandbæk, Annelli, Lauritzen, Torsten, Brunak, Søren, Kristiansen, Karsten, Li, Yingrui, Hansen, Torben, Wang, Jun, Pedersen, Oluf, and Nielsen, Rasmus

Subjects
Computational Biology, Denmark, Diabetes Mellitus, Type 2, Exome, Genetic Association Studies, Genetic Variation, Genotype, High-Throughput Nucleotide Sequencing, Humans, Models, Statistical, Open Reading Frames, Polymorphism, Single Nucleotide, White People
Abstract

It has been hypothesized that, in aggregate, rare variants in coding regions of genes explain a substantial fraction of the heritability of common diseases. We sequenced the exomes of 1,000 Danish cases with common forms of type 2 diabetes (including body mass index > 27.5 kg/m(2) and hypertension) and 1,000 healthy controls to an average depth of 56×. Our simulations suggest that our study had the statistical power to detect at least one causal gene (a gene containing causal mutations) if the heritability of these common diseases was explained by rare variants in the coding regions of a limited number of genes. We applied a series of gene-based tests to detect such susceptibility genes. However, no gene showed a significant association with disease risk after we corrected for the number of genes analyzed. Thus, we could reject a model for the genetic architecture of type 2 diabetes where rare nonsynonymous variants clustered in a modest number of genes (fewer than 20) are responsible for the majority of disease risk.

Published
2013

10. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

Author

Lohmueller, Kirk E, Albrechtsen, Anders, Li, Yingrui, Kim, Su Yeon, Korneliussen, Thorfinn, Vinckenbosch, Nicolas, Tian, Geng, Huerta-Sanchez, Emilia, Feder, Alison F, Grarup, Niels, Jørgensen, Torben, Jiang, Tao, Witte, Daniel R, Sandbæk, Annelli, Hellmann, Ines, Lauritzen, Torsten, Hansen, Torben, Pedersen, Oluf, Wang, Jun, and Nielsen, Rasmus

Subjects
Animals, Humans, Pan troglodytes, Evolution, Molecular, Recombination, Genetic, Gene Frequency, Genetic Drift, Mutation, Genome, Human, Models, Genetic, Population, Genetic Variation, Selection, Genetic, Human Genome, Biotechnology, Genetics, Generic health relevance, Developmental Biology
Abstract

A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

Published
2011

16. The association between sleep duration and detailed measures of obesity:A cross sectional analysis in the ADDITION-PRO study

Author

Andersen, Mie M., Laurberg, Tinne, Bjerregaard, Anne Louise, Sandbæk, Annelli, Brage, Søren, Vistisen, Dorte, Quist, Jonas S., Bruun, Jens M., Witte, Daniel R., Andersen, Mie M., Laurberg, Tinne, Bjerregaard, Anne Louise, Sandbæk, Annelli, Brage, Søren, Vistisen, Dorte, Quist, Jonas S., Bruun, Jens M., and Witte, Daniel R.

Abstract

Background: Sleep duration is associated with BMI and waist circumference. However, less is known about whether sleep duration affects different measurements of obesity differently. Objective: To investigate the association between sleep duration and different measures of obesity. Methods: In this cross-sectional analysis 1309, Danish, older adults (55% men) completed at least 3 days of wearing a combined accelerometer and heart rate-monitor for assessing sleep duration (hours/night) within self-reported usual bedtime. Participants underwent anthropometry and ultrasonography to assess BMI, waist circumference, visceral fat, subcutaneous fat, and fat percentage. Linear regression analyses examined the associations between sleep duration and obesity-related outcomes. Results: Sleep duration was inversely associated with all obesity-related outcomes, except visceral-/subcutaneous-fat-ratio. After multivariate adjustment the magnitude of associations became stronger and statistically significant for all outcomes except visceral-/subcutaneous-fat-ratio, and subcutaneous fat in women. The associations with BMI and waist circumference demonstrated the strongest associations, when comparing standardized regression coefficients. Conclusions: Shorter sleep duration were associated with higher obesity across all outcomes except visceral-/subcutaneous-fat-ratio. No specifically salient associations with local or central obesity were observed. Results suggest that poor sleep duration and obesity correlate, however, further research is needed to conclude on beneficial effects of sleep duration regarding health and weight loss.

Published
2023

23. Additional file 3 of The effect of virtual specialist conferences between endocrinologists and general practitioners about type 2 diabetes: study protocol for a pragmatic randomized superiority trial

Author

Prætorius, Thim, Baymler Lundberg, Anne Sofie, Søndergaard, Esben, Tang Knudsen, Søren, and Sandbæk, Annelli

Abstract

Additional file 3: Supplementary file 3. The “Diabetes Overview” containing aggregated patient data used in general practice

Published
2023
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25. The Danish Version of the Problem Areas in Diabetes-Teen (PAID-T) Scale: Translation and Linguistic Validation

Author

Rahbæk, Marie Ørts, Jensen, Sissel Due, Hansen, Karina Kudahl, Sandbæk, Annelli, Lund, Sten, and Andersen, Anette

Abstract

Introduction. Diabetes distress is often seen in adolescents with Type 1 diabetes (T1D). Problem Areas in Diabetes (PAID) is the most frequently used scale to assess diabetes distress in clinical settings, but the version for teenagers has not been translated into Danish and validated before now. Objective. This study describes the translation into Danish of the PAID-T scale, which was developed to measure emotional distress in teenagers with diabetes. Materials and Methods. The study was conducted in two phases. First, the PAID-T was translated into Danish based on the guidelines from the International Society for Pharmacoeconomics and Outcome Research and a forwardbackward translation procedure. Second, cognitive interviews were conducted, and the Danish version of the PAID-T was modified to ensure linguistic equivalence with the original scale in English. Results. The Danish version of the PAID-T questionnaire was found to be understandable and relevant for adolescents with T1D. No questions were found to be irrelevant. However, the cognitive interviews showed that the issue of balancing alcohol intake and blood sugar levels was not covered by PAID-T, although this was found relevant in the Danish target group. Conclusion. This study described the translation and linguistic validation of the PAID-T scale into Danish. After modifications based on the feedback from the cognitive interviews, the Danish version was found to be linguistically equivalent to the original English version.

Published
2023
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33. Kommunikation om vægtrelaterede problemer med patienter med svær overvægt

Author

Lindberg, Cecilie Sonne, Sandbæk, Annelli, Jensen, Sissel Due, Bruun, Jens Meldgaard, and Andreassen, Pernille

Subjects
Communication, Humans, Obesity/complications
Abstract

This review focuses on communication about weight-related issues with patients with obesity in general practice. Primary care providers still lack knowledge and tools to address and communicate about the topic of weight and weight-related issues - with focus on minimizing stigmatization and a person centered approach. A few communication tools on the topic have been developed but it seems that the use of those is limited, suggesting an urgent need for making a fast, easy and simple tool for the use in general practice.

Published
2022

49. Grant Proposal: A framework for an open and scalable infrastructure for health data exemplified by the DD2 initiative

Author

Johnston, Luke William, Kjærgaard, Alisa Devedzic, and Sandbæk, Annelli

Subjects
data engineering, FAIR data, data infrastructure, research infrastructure, open science, data science, data management, software engineering
Abstract

Many initiatives in clinical research have a difficult time getting funds for building and maintaining needed software that make sure health science is the highest quality it can be. We submitted a grant proposal to build software tools that streamline and automate aspects of collecting, managing, and sharing data. Details found on the website: https://steno-aarhus.github.io/dif-project/

Published
2022
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