| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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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.
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| 2. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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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.
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| 3. |
- Lehto, Elviira, et al.
(författare)
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Do descriptive norms related to parents and friends predict fruit and vegetable intake similarly among 11-year-old girls and boys?
- 2015
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Ingår i: British Journal of Nutrition. - Cambridge, United Kingdom : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 115:1, s. 168-175
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Tidskriftsartikel (refereegranskat)abstract
- We examined whether there are sex differences in children's fruit and vegetable (FV) intake and in descriptive norms (i.e. perceived FV intake) related to parents and friends. We also studied whether friends' impact is as important as that of parents on children's FV intake. Data from the PRO GREENS project in Finland were obtained from 424 children at the age 11 years at baseline. At baseline, 2009 children filled in a questionnaire about descriptive norms conceptualised as perceived FV intake of their parents and friends. They also filled in a validated FFQ that assessed their FV intake both at baseline and in the follow-up in 2010. The associations were examined with multi-level regression analyses with multi-group comparisons. Girls reported higher perceived FV intake of friends and higher own fruit intake at baseline, compared with boys, and higher vegetable intake both at baseline and in the follow-up. Perceived FV intake of parents and friends was positively associated with both girls' and boys' FV intake in both study years. The impact of perceived fruit intake of the mother was stronger among boys. The change in children's FV intake was affected only by perceived FV intake of father and friends. No large sex differences in descriptive norms were found, but the impact of friends on children's FV intake can generally be considered as important as that of parents. Future interventions could benefit from taking into account friends' impact as role models on children's FV intake.
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| 4. |
- Lehto, Elviira, 1953-, et al.
(författare)
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Mediation of parental educational level on fruit and vegetable intake among schoolchildren in ten European countries
- 2015
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Ingår i: Public Health Nutrition. - 1368-9800 .- 1475-2727. ; 18:1, s. 89-99
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine which factors act as mediators between parental educational level and children's fruit and vegetable (F&V) intake in ten European countries.Design: Cross-sectional data were collected in ten European countries participating in the PRO GREENS project (2009). Schoolchildren completed a validated FFQ about their daily F&V intake and filled in a questionnaire about availability of F&V at home, parental facilitation of F&V intake, knowledge of recommendations about F&V intake, self-efficacy to eat F&V and liking for F&V. Parental educational level was determined from a questionnaire given to parents. The associations were examined with multilevel mediation analyses.Setting: Schools in Bulgaria, Finland, Germany, Greece, Iceland, the Netherlands, Norway, Portugal, Slovenia and Sweden.Subjects: Eleven-year-old children (n 8159, response rate 72%) and their parents.Results: In five of the ten countries, children with higher educated parents were more likely to report eating fruits daily. This association was mainly mediated by knowledge but self-efficacy, liking, availability and facilitation also acted as mediators in some countries. Parents' education was positively associated with their children's daily vegetable intake in seven countries, with knowledge and availability being the strongest mediators and self-efficacy and liking acting as mediators to some degree.Conclusions: Parental educational level correlated positively with children's daily F&V intake in most countries and the pattern of mediation varied among the participating countries. Future intervention studies that endeavour to decrease the educational-level differences in F&V intake should take into account country-specific features in the relevant determinants of F&V intake.
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| 5. |
- Lehto, Elviira, et al.
(författare)
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Predicting gender differences in liking for vegetables and preference for a variety of vegetables among 11-year-old children
- 2015
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Ingår i: Appetite. - : Academic Press. - 0195-6663 .- 1095-8304. ; 95, s. 285-292
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Tidskriftsartikel (refereegranskat)abstract
- We studied the factors that predict liking for vegetables and preference for a variety of vegetables among schoolchildren. Additionally, we examined if there were gender differences in the predictors that explain the hypothesized higher scores in liking vegetables and preferences among girls. The data from the PRO GREENS project included 424 Finnish children (response rate 77%) aged 11 to 12. The children completed validated measures about social and environmental factors related to their liking for vegetables and preferences both at baseline 2009 and follow-up 2010. The associations were examined with regression and mediation analyses. The strongest predictors of both girls' and boys' liking and preferences were higher levels of eating vegetables together with the family, previous vegetable intake and a lower level of perceived barriers. Liking was additionally predicted by a lower level of parental demand that their child should eat vegetables. Girls reported higher levels of liking and preferences in the follow-up. This gender difference was mainly explained by girls' lower level of perceived barriers related to vegetable intake and girls' higher previous vegetable intake. Interventions that aim to increase the low vegetable intake among boys by increasing their liking for vegetables and preference for a variety of vegetables could benefit from targeting perceived barriers, namely boys' perception and values concerning the consumption of vegetables.
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| 6. |
- Lehto, Elviira, et al.
(författare)
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The ones with lowest fruit and vegetable intake benefitted of the intervention only moderately
- 2015
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Ingår i: Annals of Nutrition and Metabolism. - Basel : S. Karger. - 0250-6807 .- 1421-9697. - 9783318056310 ; 67:Suppl. 1, s. 360-361
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Infrequent fruit and vegetable (FV) intake is especially common among children with low parental educational level (PEL) and among boys.Objectives: Our aim was to examine whether a school-based intervention was efficient in increasing children’s FV intake especially among those whose FV intake is the lowest and which factors could explain the the group differences in the associations.Method / Design: In Finland 11-year-old (at baseline) children participated in the PRO GREENS intervention in winter 2009. In control schools were 424 and in intervention schools 386 children (response rate 77%). Children filled in validated food frequency questionnaire assessing FV intake (times/day) and a validated questionnaire about factors influencing FV intake (availability of FV, liking for FV, preferences, self-efficacy to eat FV, attitudes towards FV and knowledge of the recommendations) both at baseline May 2009 and follow-up May 2010. Parental educational level (low, middle, high) was reported by the parents. Associations were examined with linear regression and mediation analyses.Results: The intervention increased fruit intake among girls but not among boys. Intervention increased also children’s knowledge of the recommendations. Since knowledge had no impact on boys’ fruit intake, the increase in knowledge mediated only intervention’s effect on girls’ fruit intake. Intervention increased children’s fruit intake similarly in all PEL groups.Intervention increased vegetable intake only in the middle PEL group but no intervention effect was noted among children with low or high PEL. Knowledge, the only factor which mediated the intervention’s effect on children’s vegetable intake, could not explain PEL differences in the effectivity of the intervention.Conclusions: Increase in knowledge was not a sufficient prerequisite to increase FV intake among boys or the lowest PEL group. More in depth analyses are needed to find out which factors to target in interventions to reach an effect in the target groups.
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| 7. |
- Michael, Eva, et al.
(författare)
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Long-term follow-up and characteristic pathological findings in severe nemaline myopathy due to LMOD3 mutations
- 2019
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Ingår i: Neuromuscular Disorders. - : Elsevier BV. - 0960-8966. ; 29:2, s. 108-113
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Tidskriftsartikel (refereegranskat)abstract
- We describe the long-term follow-up of a patient with severe nemaline myopathy due to a novel homozygous mutation in the Leiomodin 3 (LMOD3) gene and describe the histopathological characteristics of the disease. The patient presented at birth with hydrops fetalis, multiple joint contractures, severe generalized muscle weakness, no movement, and respiratory insufficiency. At eight years of age, she had bilateral ophthalmoplegia, visual impairment, multiple contractures, and scoliosis, and is dependent on a home mechanical ventilator and gastrostomy. Except for slight head nodding, she has no voluntary movements. Whole-exome sequencing revealed a homozygous one-base duplication in the LMOD3 gene (c.882dupA, p.Asp295Argfs*2), which would result in a truncated protein. Muscle biopsy in the girl and an unrelated patient homozygous for LMOD3 p.G1u357* showed characteristic morphology of the nemaline rods. Many rods appeared as fragments of thickened Z-discs, frequently in pairs, which were interconnected by short thin filaments. Although not specific, this may be a morphological hallmark of LMOD3-associated nemaline myopathy.
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| 8. |
- Nätt, Daniel, et al.
(författare)
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Human sperm displays rapid responses to diet
- 2019
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Ingår i: PLoS biology. - San Francisco, CA United States : PUBLIC LIBRARY SCIENCE. - 1544-9173 .- 1545-7885. ; 17:12
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Tidskriftsartikel (refereegranskat)abstract
- The global rise in obesity and steady decline in sperm quality are two alarming trends that have emerged during recent decades. In parallel, evidence from model organisms shows that paternal diet can affect offspring metabolic health in a process involving sperm tRNA-derived small RNA (tsRNA). Here, we report that human sperm are acutely sensitive to nutrient flux, both in terms of sperm motility and changes in sperm tsRNA. Over the course of a 2-week diet intervention, in which we first introduced a healthy diet followed by a diet rich in sugar, sperm motility increased and stabilized at high levels. Small RNA-seq on repeatedly sampled sperm from the same individuals revealed that tsRNAs were up-regulated by eating a high-sugar diet for just 1 week. Unsupervised clustering identified two independent pathways for the biogenesis of these tsRNAs: one involving a novel class of fragments with specific cleavage in the T-loop of mature nuclear tRNAs and the other exclusively involving mitochondrial tsRNAs. Mitochondrial involvement was further supported by a similar up-regulation of mitochondrial rRNA-derived small RNA (rsRNA). Notably, the changes in sugar-sensitive tsRNA were positively associated with simultaneous changes in sperm motility and negatively associated with obesity in an independent clinical cohort. This rapid response to a dietary intervention on tsRNA in human sperm is attuned with the paternal intergenerational metabolic responses found in model organisms. More importantly, our findings suggest shared diet-sensitive mechanisms between sperm motility and the biogenesis of tsRNA, which provide novel insights about the interplay between nutrition and male reproductive health.
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| 9. |
- Ried, Janina S., et al.
(författare)
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 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
- 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.
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