| 1. |
- Walters, R G, et al.
(författare)
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A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 463:7281, s. 671-5
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Tidskriftsartikel (refereegranskat)abstract
- Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.
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| 2. |
- Falchi, M., et al.
(författare)
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Low copy number of the salivary amylase gene predisposes to obesity
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:5, s. 492-497
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Tidskriftsartikel (refereegranskat)abstract
- Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10-14) and serum enzyme levels (P < 2.20 × 10-16), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy =-0.15 (0.02) kg/m 2; P = 6.93 × 10-10) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13-1.26; P = 1.46 × 10-10). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies. © 2014 Nature America, Inc. All rights reserved.
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| 3. |
- Iglesia, I., et al.
(författare)
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Folate and vitamin B-12 concentrations are associated with plasma DHA and EPA fatty acids in European adolescents : the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study
- 2017
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Ingår i: British Journal of Nutrition. - : CAMBRIDGE UNIV PRESS. - 0007-1145 .- 1475-2662. ; 117:1, s. 124-133
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to examine the association between vitamin B-6, folate and vitamin B-12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43% males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6: n-3 ratio, trans-fatty acids and oleic: stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15.85 mu mol/l of EPA (P value < 0.01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2.06 mu mol/l of DHA (P value < 0.05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.
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| 4. |
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| 5. |
- Vandevijvere, S., et al.
(författare)
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Intake and dietary sources of haem and non-haem iron among European adolescents and their association with iron status and different lifestyle and socio-economic factors
- 2013
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 67:7, s. 765-772
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Tidskriftsartikel (refereegranskat)abstract
- Background/Objectives:Adolescents are at risk of iron deficiency because of their high iron requirements. The aims of this study were: (1) to assess iron intake, its determinants and its most important food sources and; (2) to evaluate the relation of iron intake and status in European adolescents. Subjects/Methods:Two non-consecutive 24-h recalls were completed by a computerised tool. The socio-demographic and socio-economic data were collected by a self-reported questionnaire. Weight and height were measured. A distinction was made between haem and non-haem iron.Results:The total iron intake was significantly higher among boys (13.8 mg/day; n=1077) than girls (11.0 mg/day; n=1253). About 97.3% of the boys and 87.8% of the girls met the estimated average requirement, and 72.4% of the boys and 13.7% of the girls met the recommendation for bio-available iron intake. The ratio of haem/non-haem iron intake was lower for girls than boys. Meat (19.2; 76%) and bread and rolls (12.6;3.9%) contributed most to total and haem iron intake. Bread and rolls (13.8%) and meat (10.8%) contributed most to non-haem iron intake. Age, sex and body mass index were associated with iron intake. Only red blood cell concentration was significantly negatively associated with total, haem and non-haem iron intake.Conclusion:Girls had lower iron intakes and ratio of haem/non-haem iron intake than boys. The main total iron and haem iron source was meat, while the main non-haem iron source was bread and rolls. Adolescent girls may be a group at risk for iron deficiency. Consequently, special attention and strategies are needed in order to improve iron intakes during adolescence.
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| 8. |
- Gillberg, L., et al.
(författare)
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Nitric oxide pathway-related gene alterations in inflammatory bowel disease
- 2012
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 47:11, s. 1283-1297
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To reveal specific gene activation in nitric oxide (NO)-related inflammation we studied differential gene expression in inflammatory bowel disease (IBD). Methods. Total RNA was isolated from 20 biopsies of inflamed mucosa from Crohn's disease (CD) and ulcerative colitis (UC) patients each as well as from six controls, labeled with 32P-dCTP and hybridized to a human NO gene array. Significant genes were analyzed for functional gene interactions and heatmaps generated by hierarchical clustering. A selection of differentially expressed genes was further evaluated with immunohistochemical staining. Results. Significant gene expression differences were found for 19 genes in CD and 23 genes in UC compared to controls, both diseases with high expression of ICAM1 and IL-8. Correlation between microarray expression and corresponding protein expression was significant (r 0.47, p 0.002). Clustering analysis together with functional gene interaction analysis revealed clusters of coregulation and coexpression in CD and UC: transcripts involved in angiogenesis, inflammatory response mediated by the transcription factor hypoxia-inducible factor 1, and tissue fibrosis. Also, a fourth cluster with transcripts regulated by the transcription factor Sp1 was found in UC. Conclusions. Expression analysis in CD and UC revealed disease-specific regulation of NO-related genes, which might be involved in perpetuating inflammatory disease activity in IBD.
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| 9. |
- Orsini, N, et al.
(författare)
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Profile of physical activity behaviors among Swedish women aged 56-75 years.
- 2008
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 18:1, s. 95-101
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess profiles of physical activity (PA) behavior using accelerometers among middle-aged and elderly women in free-living conditions. A subset of 133 women aged 56-75 years from the population-based Swedish Mammography Cohort with valid accelerometer data was included in the analysis. The proportion of women who met the PA recommendation of accumulating 30 min of moderate-to-vigorous physical activity (MVPA), in either one continuous bout or several shorter bouts lasting 8-10 min, on five or more days/week was 31%. The precision of mean daily estimates of MVPA and of inactivity based on 7 days monitoring was 0.80 and 0.86, respectively. On average, participants spent 103 min/day on MVPA, but only about a third of that time was accumulated in the recommended pattern of bouts lasting at least 8-10 min. Obese women had, on average, one bout of MVPA less than normal-weight women (mean 3.6 bouts/day). The mean MVPA decreased 10 min/day with every 5-year increase in age. A low proportion of women accumulated MVPA in the pattern recommended for health benefits. The proportion would increase considerably if women maintained their current amount of MVPA but increased the duration of each bout of MVPA.
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| 10. |
- Apollonio, M., et al.
(författare)
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Improved Emittance and Brightness for the MAX IV 3 GeV Storage Ring
- 2022
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Ingår i: Proc. IPAC'22. - 9783954502271 ; , s. 288-291
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- At MAX IV Laboratory, the Swedish Synchrotron Radiation (SR) facility, the largest of two rings operates at 3 GeV with a bare lattice emittance of 330 pm rad. Upgrade plans are under consideration aiming at a gradual reduction of the emittance, in three stages: a short-term with an emittance reduction of 20% to 40%, a mid-term with an emittance reduction of more than 50% and a long-term with an emittance in the range of the diffraction limit for hard X-rays (10 keV). In this paper we focus on the short-term case, resuming previous work on a proposed lattice that can reach 270 pm rad emittance, with only minor modifications to the gradients of the magnets of the present ring, i.e. without any hardware changes and all within the present power supply limits. Linear lattice characterisation and calculations of key performance parameters, such as dynamic aperture and momentum aperture with errors, are described and compared to the present operating lattice. Experimental tests of injection into this lattice are also shown.
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