| 1. |
- Willems, S. M., et al.
(författare)
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Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality. © The Author(s) 2017.
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| 2. |
- Lauria, F., et al.
(författare)
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A common variant and the transcript levels of MC4R gene are associated with adiposity in children: The IDEFICS study
- 2016
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 101:11, s. 4229-4236
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Tidskriftsartikel (refereegranskat)abstract
- Context: The melanocortin-4 receptor gene (MC4R) plays a pivotal role in the regulation of body fat and food and energy intake. Objectives: The objectives of the study were as follows: 1) to evaluate the association of variants rs17782313 and rs17700633 near the coding region of MC4R and 2) to evaluate the association of the transcript levels of MC4R with adiposity indices and percentage of energy from fat, carbohydrates, and protein in children. Design: The Identification and Prevention of Dietary-and Lifestyle-Induced Health Effects in Children and Infants (IDEFICS) cohort was used, with examinations at baseline (T0) and after 2 years (T1). Setting and Participants: A total of 16 228 schoolchildren (2-9 y) from eight European countries participated in the study. A random sample of 4381 children genotyped for MC4R variants and a subsample of 410 children with MC4R expression data in peripheral blood cells (PBCs) were included in the analyses. Main Outcome Measures: Anthropometric measures and energy intake (total and from fat, carbohydrates, and protein) served as outcomes for adiposity status and for dietary behavior, respectively. Results: At T0, the C allele of rs17782313 (minor frequency allele 23%) was significantly associated with higher values of adiposity indices (all P<.001).Noassociation was found between rs17700633 (minor frequency allele 28%) and the variables under study. At T1, the C allele of rs17782313 was associated with a significantly higher increase in the adiposity indices over time (all P < .05). The MC4R expression levels in PBCs were inversely associated with body fat and energy intake from carbohydrates and directly with energy from fat (all P ≤ .05) but were not influenced by variants rs17782313 and rs17700633. Conclusions: The common variant rs17782313 near MC4R was cross-sectionally and longitudinally associated with body mass index and measures of body fatness in children aged 2-9 years. We showed, for the first time in humans, that MC4R expression levels in PBCs are related to body fat distribution and percentage of energy intake from carbohydrates and fat. (J Clin Endocrinol Metab 101: 4229-4236, 2016). Copyright © 2016 by the Endocrine Society.
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| 3. |
- Foraita, R, et al.
(författare)
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Does the FTO gene interact with the socioeconomic status on the obesity development among young European children? Results from the IDEFICS study.
- 2015
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 39, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Background:Various twin studies revealed that the influence of genetic factors on psychological diseases or behaviour is more expressed in socioeconomically advantaged environments. Other studies predominantly show an inverse association between socioeconomic status (SES) and childhood obesity in Western developed countries. The aim of this study is to investigate whether the fat mass and obesity-associated (FTO) gene interacts with the SES on childhood obesity in a subsample (N=4406) of the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS) cohort.Methods:A structural equation model (SEM) is applied with the latent constructs obesity, dietary intakes, physical activity and fitness habits, and parental SES to estimate the main effects of the latter three variables and a FTO polymorphism on childhood obesity. Further, a multiple group SEM is used to explore whether an interaction effect exists between the single nucleotide polymorphism rs9939609 within the FTO gene and SES.Results:Significant main effects are shown for physical activity and fitness (standardised [betacrc ](s) = -0.113), SES ([betacrc ](s) = -0.057) and the FTO homozygous AA risk genotype ([betacrc ](s) = -0.177). The explained variance of obesity is ~9%. According to the multiple group approach of SEM, we see an interaction between SES and FTO with respect to their effect on childhood obesity (Δχ(2)=7.3, df=2, P=0.03).Conclusion:Children carrying the protective FTO genotype TT seem to be more protected by a favourable social environment regarding the development of obesity than children carrying the AT or AA genotype.International Journal of Obesity advance online publication, 23 September 2014; doi:10.1038/ijo.2014.156.
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