| 1. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Flannick, Jason, et al.
(författare)
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Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:4, s. 357-357
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Tidskriftsartikel (refereegranskat)abstract
- Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ∼150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.
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| 3. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)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.
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| 4. |
- Groundstroem, Henrik, et al.
(författare)
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A systematic mapping of Nordic youth surveys
- 2020
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Konferensbidrag (refereegranskat)abstract
- Aim: The aim of this study was to map the existing Nordic youth surveys and to answer the following research questions: how many youth surveys are conducted in the Nordic countries?, what major youth surveys are being conducted in all Nordic countries?, and what themes do the existing questionnaires deal with in the various countries?Method: Data was collected from January to April 2018 through a systematic mapping technique and the surveys were analyzed according to quality criteria.Results: The results showed a total of 143 surveys and after exclusion due to poor survey quality, 82 fit the inclusion criteria. In the Nordic countries, six surveys were identified that covered all Nordic countries. The themes that youth surveys usually focus on are criminality, school, physical and mental health, addiction, societal participation and family relationships.Conclusion: Many similar youth surveys exist both nationally and on a Nordic level. During the last forty years, there has also been an exponential increase in surveys aimed at young people. A larger coordination of these surveys would be beneficial and increase their quality as well as limit the number of surveys that young people are exposed to. This study identifies the need for a coordinated Nordic youth survey and the potential benefits on a regional, national and Nordic level.
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| 5. |
- Hubel, Christopher, et al.
(författare)
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Latent anxiety and depression dimensions differ amongst patients with eating disorders : A Swedish nationwide investigation
- 2023
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Ingår i: International Journal of Methods in Psychiatric Research. - : John Wiley & Sons. - 1049-8931 .- 1557-0657. ; 32:3
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveAnxiety and depression symptoms are common in individuals with eating disorders. To study these co-occurrences, we need high-quality self-report questionnaires. The 19-item self-rated Comprehensive Psychopathological Rating Scale for Affective Syndromes (CPRS-S-A) is not validated in patients with eating disorders. We tested its factor structure, invariance, and differences in its latent dimensions.MethodPatients were registered by 45 treatment units in the Swedish nationwide Stepwise quality assurance database for specialised eating disorder care (n = 9509). Patients self-reported their anxiety and depression symptoms on the CPRS-S-A. Analyses included exploratory and confirmatory factor analyses (CFA) in split samples, and testing of invariance and differences in subscales across eating disorder types.ResultsResults suggested a four-factor solution: Depression, Somatic and fear symptoms, Disinterest, and Worry. Multigroup CFA indicated an invariant factor structure. We detected the following differences: Patients with anorexia nervosa binge-eating/purging subtype scored the highest and patients with unspecified feeding and eating disorders the lowest on all subscales. Patients with anorexia nervosa or purging disorder show more somatic and fear symptoms than individuals with either bulimia nervosa or binge-eating disorder.ConclusionOur four-factor solution of the CPRS-S-A is suitable for patients with eating disorders and may help to identify differences in anxiety and depression dimensions amongst patients with eating disorders.
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| 6. |
- Reas, Deborah Lynn, et al.
(författare)
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Clinicians as a critical link : Understanding health professionals' beliefs and attitudes toward anorexia nervosa, bulimia nervosa, and binge eating disorder
- 2021
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Ingår i: Scandinavian Journal of Psychology. - : John Wiley & Sons. - 0036-5564 .- 1467-9450. ; 62:6, s. 775-779
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the perspectives of health professionals remains an understudied issue, yet may help bridge research-practice gaps and pinpoint important areas for education, training, and research. This study investigated attitudes toward anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) among Nordic health professionals specialized within the eating disorder (ED) field. Participants (n = 144) completed a modified ED-version of the Illness Perception Questionnaire which assessed attitudes and beliefs toward perceived symptom controllability, severity, treatment effectiveness, and views on the prognosis of AN, BN, and BED. Personal enjoyment and level of comfort working with AN, BN, and BED were also assessed. The majority agreed or strongly agreed that patients with AN, BN, and BED were not responsible for their illness, and viewed the illnesses as psychological rather than medical in etiology. AN was viewed as the most severe and enduring, followed by BN, then BED. Treatment for BN was viewed as being more highly effective than treatments for either AN or BED. Professionals rated significantly less enjoyment and less confidence working with BED. To conclude, both commonalities and differences in attitudes toward AN, BN and BED were found in terms of perceived symptom controllability, views on severity, treatment effectiveness, and anticipated prognosis. In particular, findings emphasized the need for additional training in the management of BED among Nordic healthcare professionals.
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