| 1. |
- Mahajan, Anubha, et al.
(författare)
-
Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
-
Tidskriftsartikel (refereegranskat)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. |
- Saxena, Richa, et al.
(författare)
-
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
- 2007
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336
-
Tidskriftsartikel (refereegranskat)abstract
- New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
|
|
| 3. |
- Surendran, Praveen, et al.
(författare)
-
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
|
|
| 4. |
- Aarsand, Pål, et al.
(författare)
-
Appropriation through guided participation : Media literacy activities in children's everyday lives
- 2016
-
Ingår i: Discourse, Context & Media. - : Elsevier BV. - 2211-6958 .- 2211-6966. ; 12, s. 20-31
-
Tidskriftsartikel (refereegranskat)abstract
- This article explores media literacy practices in children’s everyday lives and some of the ways in which young children appropriate basic media literacy skills through guided participation in situated activities. Building on an ethnomethodological perspective, the analyses are based on video recordings documenting the activities in which four target children, aged 6-7 years old, participated at home and in school. Through the detailed analysis of two mundane media literacy activities – online calling and word processing – similarities and differences in media usage within and out-of-school are examined. It is shown how children’s media literacy activities encompass verbal, embodied and social competencies that are made relevant, and thus accessible for learning, in interaction between the adults and children in the form of norms and guidelines for what constitutes knowledgeable participation in media literacy activities, and that are appropriated and reactualized by the children in interaction with their peers. The findings show how the participants coordinate their actions on and in front of the screen and where spatiality and temporality are oriented to as crucial aspects of the organization of the activities. Moreover, it is demonstrated how old and new technologies are linked together in culturally and historically embedded conceptualizations of literacy.
|
|
| 5. |
- Aarsand, Pål, et al.
(författare)
-
Digital literacy practices in children's everyday life. : Participating in on-screen and off-screen activities.
- 2019
-
Ingår i: The Routledge Handbook of Digital Literacies in Early Childhood. - London : Routledge. - 9781138303881 ; , s. 377-390
-
Bokkapitel (refereegranskat)abstract
- This chapter focuses on young children’s use of digital technologies and on participation in situated digital literacy practices within and across activities and institutional settings. First, we present a review of research focusing on digital literacy as embedded in children’s everyday lives and on multimodal engagements with and around digital technologies together with peers, siblings and adults. Second, we explore three mundane activities involving different participant constellations, technologies and settings, using an ethnomethodological and conversation analytic approach in order to discuss theoretical challenges related to the idea that digital literacies are situated.
|
|
| 6. |
- Aarsand, Pål, et al.
(författare)
-
Om media literacy-praktiker i barns vardagsliv
- 2013
-
Ingår i: Literacy-praktiker i och utanför skolan. - Stockholm : Gleerups Utbildning AB. - 9789140684455 ; , s. 41-63
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 7. |
- Abrahamsson, Emma, 1978-
(författare)
-
Att formulera problem i barnpsykiatriska samtal
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present study explores problem-formulation processes in Swedish child and adolescent psychiatry (Sw. Barn- och ungdomspsykiatri, BUP), drawing on an ethnomethodological conversation analytic approach to institutional talk. Data consists of video and audio recordings of 15 initial assessments, one therapeutic contact (six sessions) and one neuropsychiatric assessment (12 sessions), with children and adolescents aged 10 to 17. Shorter sequences as well as longer processes spanning several sessions are analyzed. While much prior research has examined caregiver-clinician interaction in cases involving younger children, the present study explicitly focuses on the child as an active participant.The analyses of the initial assessments demonstrate how children resist caregivers’ problem formulations by presenting alternative versions of these formulations that draw on their in-depth knowledge of their own everyday life. Clinicians’ strategies of orchestrating the talk in these sequences are shown to be critical in balancing children’s and caregivers’ relative epistemic status. In the therapeutic interactions, the analyses focus on how the participants use reported speech as an interactional resource to illustrate problematic communication patterns in the family, to model alternative courses of action, and to communicate therapeutic change. In these encounters, the child takes an active role in the process of problem formulation. Finally, neuropsychiatric assessment interactions are analyzed with a focus on the clinical sense-making process through which a shared understanding of the child’s problems is negotiated in initial and concluding phases of the contact.Through attending to clinical sense-making in negotiations between adolescents and caregivers, the study provides nuance to the image of medical interaction as primarily characterized by tensions between contrasting life-world and medical perspectives. The concluding discussion addresses how knowledge claims and conflicting versions of psychiatric problems are managed in multi-party interactions, as well as how boundaries between normality and deviance are negotiated in processes of interaction.
|
|
| 8. |
- Abreu Fernandes, Olga, et al.
(författare)
-
Designedly incomplete utterances as prompts for co-narration in home literacy events with young multilingual children
- 2022
-
Ingår i: Linguistics and Education. - : Elsevier. - 0898-5898 .- 1873-1864. ; 71
-
Tidskriftsartikel (refereegranskat)abstract
- This video-ethnographic study investigates how designedly incomplete utterances (DIUs) are used during home literacy events in three bilingual families with young chidlren in Sweden to prompt collaborative storybook reading in the chidlren's heritage language, Russian. The multimodal interactional analyses uncover how DIUs, in concert with other semiotic resources, create a sequential environment to prompt chidlren's speech production in relation to the text at hand, to negotiate language choice and alignment with an ongoing literacy project, and to creatively exploit the DIU structure to initiate storytelling. The findings moreover show that recurrent use of DIUs during reading of well-known to teh child texts with rhythm and rhyme allow for ritualized engagemnet in co-narration, in all contributing to children's socialization to oral performance in the heritage language.
|
|
| 9. |
- Abreu Fernandes, Olga
(författare)
-
Nurturing a heritage language : Language-centered practices in mother-child interactions in multilingual families
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Situated within research on language socialization and family language policy, this thesis explores how young children (2–4 years old) learn their heritage language in multilingual, transnational families, and how multilingualism becomes an integral part of family life. It draws on video-ethnographic fieldwork in three bi/multilingual families in Sweden with preschool-aged children where the mothers speak Russian and the parents aspire to raise children multilingually.Using a multimodal interactional analysis, the three studies identify and examine recurrent language practices that promote the children’s use of the heritage language, Russian, in mother-child interactions. They approach heritage language maintenance as embedded in mundane activities such as home language lessons during collaboratively accomplished chores (Study I), conversational storytelling during mealtime (Study II), and co-narration during literacy events (Study III).The analyses focus on the interactional organization of language learning agendas and heritage language socialization environments that are initiated by the mothers to scaffold their children’s learning and use of Russian. In particular, this study illuminates various ways to engage the children in collaborative Russian speech production, including mutually enjoyable embodied performances. Moreover, it is shown in detail how high expectations of children as heritage language speakers and learners and educational efforts are interactionally balanced through relational work.The findings suggest that the realization of family language policy to support heritage language development relies not only on consistent language choice, frequency of language use, and parental strategies and ideologies, but also on how language choice and language use are embedded in the ongoing activity, how activity formats are organized and appropriated by the children, the position of the child as a speaker vis-à-vis the parent, and affective alignments. The study uncovers an interplay of educational, relational, ideological, and pragmatic dimensions of heritage language socialization in the home. In this way, the thesis contributes to a more nuanced understanding of family language policy and children’s emergent multilingualism as integrated in everyday family life.
|
|
| 10. |
- Arora, Geeti P, et al.
(författare)
-
Phenotypic and genotypic differences between Indian and Scandinavian women with gestational diabetes mellitus
- 2019
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 286:2, s. 192-206
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Gestational diabetes mellitus (GDM) is a transient form of diabetes characterized by impaired insulin secretion and action during pregnancy. Population-based differences in prevalence exist which could be explained by phenotypic and genetic differences. The aim of this study was to examine these differences in pregnant women from Punjab, India and Scandinavia.METHODS: 85 GDM/T2D loci in European and/or Indian populations from previous studies were assessed for association with GDM based on Swedish GDM criteria in 4018 Punjabi Indian and 507 Swedish pregnant women. Selected loci were replicated in Scandinavian cohorts, Radiel (N=398, Finnish), STORK/STORK-G (N=780, Norwegian).RESULTS: Punjabi Indian women had higher GDM prevalence, lower insulin secretion and better insulin sensitivity than Swedish women. There were significant frequency differences of GDM/T2D risk alleles between both populations. rs7178572 at HMG20A, previously associated with GDM in South Indian and European women was replicated in North Indian women. The T2D risk SNP rs11605924 in the CRY2 gene was associated with increased GDM risk in Scandinavian but decreased risk in Punjabi Indian women. No other overlap was seen between GDM loci in both populations.CONCLUSIONS: GDM is more common in Indian than Swedish women, which partially can be attributed to differences in insulin secretion and action. There was marked heterogeneity in the GDM phenotypes between the populations which could only partially be explained by genetic differences. This article is protected by copyright. All rights reserved.
|
|
