| 1. |
- Locke, Adam E, et al.
(författare)
-
Genetic studies of body mass index yield new insights for obesity biology.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
|
|
| 2. |
- Shungin, Dmitry, et al.
(författare)
-
New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
-
Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
|
|
| 3. |
- Turcot, Valerie, et al.
(författare)
-
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
|
|
| 4. |
- Cunha, Ana G., et al.
(författare)
-
Surface Structuring and Water Interactions of Nanocellulose Filaments Modified with Organosilanes toward Wearable Materials
- 2018
-
Ingår i: ACS APPLIED NANO MATERIALS. - : AMER CHEMICAL SOC. - 2574-0970. ; 1:9, s. 5279-5288
-
Tidskriftsartikel (refereegranskat)abstract
- Colloidal dispersions of cellulose nanofibrils (CNFs) are viable ternatives to cellulose II dissolutions used for filament spinning. e porosity and water vapor affinity of CNF filaments make them itable for controlled breathability. However, many textile plications also require water repellence. Here, we investigated the fects of postmodification of wet-spun CNF filaments via chemical vapor position (CVD). Two organosilanes with different numbers of methyl bstituents were considered. Various surface structures were achieved, ther as continuous, homogeneous coating layers or as ree-dimensional, hairy-like assemblies. Such surface features reduced e surface energy, which significantly affected the interactions with ter. Filaments with water contact angles of up to 116 were obtained, d surface energy measurements indicated the possibility of developing phiphobicity. Dynamic vapor sorption and full immersion experiments re carried out to inquire about the interactions with water, whether the liquid or gas forms. Mechanical tests revealed that the wet rength of the modified filaments were almost 3 times higher than that the unmodified precursors. The hydrolytic and mechanical stabilities the adsorbed layers were also revealed. Overall, our results shed ght on the transformation of aqueous dispersions of CNFs into laments that are suited for controlled interactions with water via ncurrent hydrolysis and condensation reactions in CVD, while intaining the moisture buffering capacity and breathability of related ructures.
|
|
| 5. |
- Sundquist, Jan, et al.
(författare)
-
Long-term improvements after mindfulness-based group therapy of depression, anxiety and stress and adjustment disorders : A randomized controlled trial
- 2019
-
Ingår i: Early Intervention in Psychiatry. - : Wiley. - 1751-7885. ; 13:4, s. 943-952
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Although mindfulness-based group therapies (MGTs) for depressive, anxiety or stress and adjustment disorders are promising, there is a substantial lack of knowledge regarding the long-term improvements after such therapies in these common psychiatric disorders. Methods: Two hundred and fifteen patients were randomized in a randomized clinical trial (RCT) (ClinicalTrials.gov ID: NCT01476371) conducted in 2012 at 16 primary healthcare centres in southern Sweden. The patients were randomized to MGT or treatment as usual (TAU) and completed four psychometric self-rated scales after 8 weeks of treatment. Approximately 12months after the completion of the 8-week treatment, the same scales were repeated. Ordinal and generalized linear-mixed models, adjusted for cluster effects, were used for the analysis. Results: For all four psychometric scales (MADRS-S [Montgomery-Åsberg Depression Rating Scale-S], HADS-D, HADS-A [Hospital Anxiety and Depression Scale A and D] and PHQ-9 [Patient Health Questionnaire-9]) the scores at the 1-year follow-up were significantly improved (all P values <0.001) in both groups. Furthermore, there were no significant differences between the MGT and TAU in the psychometric scores at the 1-year follow-up. Conclusions: To the best of our knowledge, this is the first RCT comparing the long-term improvements after MGT with TAU. Although it cannot be excluded that our findings are a result of the natural course of common psychiatric disorders or other factors, they suggest a long-term positive improvement after both MGT and TAU.
|
|
