| 1. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 2. |
- Sarwar, Nadeem, et al.
(författare)
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Interleukin-6 receptor pathways in coronary heart disease : a collaborative meta-analysis of 82 studies
- 2012
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Ingår i: The Lancet. - New York, NY, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9822, s. 1205-1213
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Tidskriftsartikel (refereegranskat)abstract
- Background: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
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| 3. |
- Svedberg, Gudrun, et al.
(författare)
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“Do you really want to hear me out?” : young people with varying dis/abilities about their research participation
- 2012
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Konferensbidrag (refereegranskat)abstract
- Biographical research where “young people at risk” tell their story in some respect, has increased in quantity in the last two decades. Such social or educational research quite regularly pays attention to gender, ethnicity or social class. Disability is however more rarely dealt with. Maybe this has to do with the voices of disabled people not having been taken seriously in previous research as well as in society at large (cf. Munger & Mertens 2011; Rönnberg et al. 2011). Other possible reasons might be that such research is considered to involve specific methodological difficulties and is associated with rigorous ethical vetting. In this paper we explore methodological and ethical challenges and research strategies concerning interviewing young people with diverse dis/abilities. Conceptually the paper draws on arguments for involving young people in biographical research and inclusive disability research. Some arguments relate to the idea that (disadvantaged) young people should be given a voice and can contribute to knowledge about their experiences, viewpoints and circumstances (cf. Bynes & Rickards 2011; Conolly 2008). Other motives are, for example, that biographical methods may bring research, practice and policy into closer connection (Chamberlain 2002) and that multiple voices makes it possible to see difficulties not only as individual but also as structural (Atkinson 1997). In previous inclusive research focusing on methodological issues there is, however, an angle that is mainly – and paradoxically – disregarded, i.e. that young peoples’ opinions about their research participation seem to be neglected in favour of researchers’ understanding of methodological challenges and strategies. Hence, the paper aims to increase the knowledge of disabled young peoples’ views on their research participation: What are their considerations and motives for the research participation? What critical aspects of the research participation do they identify? What are their opinions on how researchers should encounter young people? Finally, the authors discuss the importance of considering respondents’ views on their research participation to decide on research strategies to encounter challenges when interviewing young people with varying dis/abilities.MethodThe results are based on two interview studies involving 47 young people and young adults living in eight Swedish municipalities, strategically selected for context diversity. A common feature of all respondents is that they have some kind of disability (chiefly learning disabilities or attention-deficit/hyperactivity disorder, ADHD), are in transitional circumstances – from school to work, starting their adult life, etc. –, and lack a diploma from upper secondary school resulting in enhanced difficulties on the labour market, no entry to tertiary education, etc. One study involves 21 young adults (9 women and 12 men) 20-30 (on average 22) years old, registered at a public employment office as having a disability. The other study involves 28 (17 women and 11 men) final-year students (19-20 years old) at upper secondary special schools for people with intellectual disability and/or autism. The individual semi-structured interviews were conducted in the respondents’ hometown in 2011, took around one hour to carry out and were recorded (with a few exceptions). The study is part of a research project – Troublesome transitions: School-to-work transitions of young people at risk in a longitudinal perspective – funded by the Swedish Research Council.Expected OutcomesWhen asked about their research participation the young adults pay great attention to informa-tion about the participation and the researchers’ responses when verbally giving their informed consent before the interview. They have various motives for their research participation, but their most common reason is however to make their voices heard to make an impact on research and, hopefully, contribute to improving the conditions for (disadvantaged) young people. Regarding the interview situation the young disabled respondents pinpoint aspects referring to the participant-researcher interaction, i.e. the importance of understanding each other and of creating a comfortable interview alliance. They value, for example, being under-stood and appreciated with respect to their ability, health or poor circumstances at the time of the interview. Sensible approaches to in biographical studies are important, not least when involving young people with varying dis/ablities. The authors argue that researchers are re-sponsible for creating good conditions, and the present study is intended to add to the knowl-edge of such challenges and research strategies. Even though our findings show that the re-spondents pay attention to the same critical methodological aspects that the authors as well as previous research observe, the respondents’ views of those aspects are important.ReferencesAtkinson, Dorothy (1997). An Auto/Biographical Approach to Learning Disability Research. Aldershot, Ashgate. Bynes, Linda J. & Rickards, Field W. (2011). Listening to the Voices of Students With Disabilities: Can Such Voices Inform Practice? Australasian Journal of Special Education, 35:1, 25-34. Chamberlayne, Prue (2002). Conclusions: social transition and biographical work. In: Chamberlayne, Prue; Rustin, Michael & Wengraf, Tom (eds). Biogra-phy and Social Exclusion in Europe. Experiences and life journeys. Bristol: Policy Press. Conolly, Anna (2009). Challenges of Generating Qualitative Data with Socially Excluded Young People. International Journal of Social Research Methodology, 11:2, 201-214. Munger, Kelly M & Mertens, Donna M. (2011). Conducting Research with the Disability Community: A Rights-Based Approach. New Directions for Adult and Continuing Education, 132: 23-33. Rönnberg, Jerker; Classon, Elisabeth, Danermark, Berth; Karlsson, Thomas (2011). Forskning om funktionsnedsättning och funktionshinder 2002-2010 (Research about impairment and disability 2002-2010). Swedish Council for Working Life and Social Research (in Swedish).
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