| 1. |
- Mahajan, Anubha, et al.
(author)
-
Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
-
Journal article (peer-reviewed)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
|
|
| 2. |
|
|
| 3. |
- Ried, Janina S., et al.
(author)
-
A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
|
|
| 4. |
- Östergren, Rickard, 1975-, et al.
(author)
-
Learning declarative knowledge in special education treatment group
- 2018
-
In: journal of education and training. - Las Vegas, NV, United States : Macrothink Institute, Inc.. - 2330-9709. ; 5:1
-
Journal article (peer-reviewed)abstract
- An organizing structure that in recent years has had a major impact on how to work with students who don’t respond to regular instruction is Response to Intervention (RTI). Efforts in RTI are divided into three different tiers of instruction: primary, secondary and tertiary. In our study, we investigate the impact of intensive secondary-tier instruction on students’ knowledge of basic combinations of digits in addition. We also focus on how the students develop their use of more advanced calculations in addition during the intervention.The results showed that students became faster at performing simple addition tasks, which indicates that their fluency – declarative knowledge – developed during the intervention phase. Our results thereby strengthen suggestions that a secondary-tier intervention level should take place in a small group of students 20-40 minutes four to five times a week. Meanwhile, the students developed their ability to solve two-digit arithmetic tasks in addition and subtraction, which could be explained by the fact that students had automated simple number combinations and thus could focus on the calculation procedure.
|
|
| 5. |
|
|
| 6. |
- Flannick, Jason, et al.
(author)
-
Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
-
In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
-
Journal article (peer-reviewed)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
|
|
| 7. |
- Fuchsberger, Christian, et al.
(author)
-
The genetic architecture of type 2 diabetes
- 2016
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
-
Journal article (peer-reviewed)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
|
|
| 8. |
- Gabrielsson, Sebastian, 1975-, et al.
(author)
-
Sjuksköterska i psykiatrisk heldygnsvård - Lärobok för rebeller
- 2023. - 1
-
Book (other academic/artistic)abstract
- I de flesta arbetsgrupper finns de som gör saker annorlunda och ofta lyckas bättre än andra i patientarbetet; som lyckas vinna förtroende hos patienter och anhöriga; som tryggar, stärker och förmedlar hopp; som är kreativa och vågar pröva oväntade lösningar; som inte drar sig för att ifrågasätta rådande arbetssätt när det ligger i patientens bästa. Vi väljer att kalla dem goda rebeller.Ett huvudfokus i den här boken är att försöka beskriva, problematisera och ge en teoretisk och praktisk förståelse för vad det är dessa goda rebeller gör. Bokens andra huvudfokus är att beskriva hinder och möjligheter för ett sådant rebelledarskap. Den här boken förmedlar verktyg som stärker självständiga sjuksköterskor som värdesätter kunskap och prioriterar möten med människor. Den visar att mycket av den aktuella omvårdnadsforskningen är högst relevant och kan bidra till att utveckla vården, eftersom den söker svar på just de frågor som personal, patienter och anhöriga i psykiatrisk heldygnsvård brottas med i vardagen. Boken ingjuter hopp hos den som vill bidra till en personcentrerad psykiatrisk heldygnsvård som främjar återhämtning.Sjuksköterska i psykiatrisk heldygnsvård vänder sig till blivande sjuksköterskor i psykiatrisk vård och kan användas som kurslitteratur inom sjuksköterskeprogrammet och specialistsjuksköterskeprogrammet, inriktning psykiatrisk vård. Även redan yrkesverksamma har nytta av att läsa boken.
|
|
| 9. |
- Godbolt, Alison K., et al.
(author)
-
Associations between care pathways and outcome 1 year after severe traumatic brain injury
- 2015
-
In: The journal of head trauma rehabilitation. - Philadelphia : Lippincott Williams & Wilkins. - 0885-9701 .- 1550-509X. ; 30:3, s. E41-E51
-
Journal article (peer-reviewed)abstract
- Objective: To assess associations between real-world care pathways for working-age patients in the first year after severe traumatic brain injury and outcomes at 1 year.Setting and Design: Prospective, observational study with recruitment from 6 neurosurgical centers in Sweden and Iceland. Follow-up to 1 year, independently of care pathways, by rehabilitation physicians and paramedical professionals.Participants: Patients with severe traumatic brain injury, lowest (nonsedated) Glasgow Coma Scale score 3 to 8 during the first 24 hours and requiring neurosurgical intensive care, age 18 to 65 years, and alive 3 weeks after injury.Main Measures: Length of stay in intensive care, time between intensive care discharge and rehabilitation admission, outcome at 1 year (Glasgow Outcome Scale Extended score), acute markers of injury severity, preexisting medical conditions, and post-acute complications. Logistic regression analyses were performed.Results: A multivariate model found variables significantly associated with outcome (odds ratio for good outcome [confidence interval], P value) to be as follows: length of stay in intensive care (0.92 [0.87-0.98], 0.014), time between intensive care discharge and admission to inpatient rehabilitation (0.97 [0.94-0.99], 0.017), and post-acute complications (0.058 [0.006-0.60], 0.017).Conclusions: Delays in rehabilitation admission were negatively associated with outcome. Measures to ensure timely rehabilitation admission may improve outcome. Further research is needed to evaluate possible causation.
|
|
| 10. |
- Justice, Anne E., et al.
(author)
-
Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
-
Journal article (peer-reviewed)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
|
|
