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- Jacobsson, Josefin, et al.
(författare)
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Genetic variants near the MGAT1 gene are associated with body weight, BMI and fatty acid metabolism among adults and children
- 2012
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 36:1, s. 119-129
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Recently a genome-wide association analysis from five European populations identified a polymorphism located downstream of the mannosyl-(α-1,3)-glycoprotein-β-1,2-N-acetylglucosaminyltransferase (MGAT1) gene that was associated with body-weight. In the present study, associations between MGAT1 variants combined with obesity and insulin measurements were investigated in three cohorts. Levels of fatty acids and estimated measures of Δ desaturases were also investigated among adult men. Design: Six polymorphisms downstream of MGAT1 were genotyped in a cross-sectional cohort of 1152 Swedish men. Three polymorphisms were further analyzed in a case-control study of 1076 Swedish children and in a cross-sectional study of 2249 Greek children. Results: Three polymorphisms, rs12186500 (odds ratio (OR): 1.892, 95% confidence interval (CI): 1.237-2.895, P=0.003), rs1021001 (OR: 2.102, 95% CI: 1.280-3.455, P=0.003) and rs4285184 (OR: 1.587, 95% CI: 1.024-2.459, P=0.038) were associated with a higher prevalence of obesity among the adult men and a trend for obesity was observed for rs4285184 among the Swedish (OR: 1.205, 95% CI: 0.987-1.471, P=0.067) and Greek children (OR: 1.192, 95%CI: 0.978-1.454, P=0.081). Association with body weight was observed for rs12186500 (P=0.017) and rs4285184 (P=0.024) among the men. The rs1021001 and rs4285184 were also associated with body mass index (BMI) in the two Swedish cohorts and similar trends were observed among the Greek children. The combined effect size for rs1021001 and rs4285184 on BMI z-score from a meta-analysis was 0.233 (95% CI:0.093-0.373, P=0.001) and 0.147 (95% CI:0.057-0.236, P=0.001), respectively. We further observed associations between the genetic variants and fatty acids (P<0.039) and estimated measures of Δ desaturases (P<0.040), as well as interactions for rs12186500 (P<0.019) with an effect on BMI. No association was found with homeostatic model assessment-insulin resistance in any cohort but increased insulin levels, insulin response and decreased insulin sensitivity were observed among the children (P<0.038). Conclusion: Genetic variants downstream MGAT1 seem to influence susceptibility to obesity. Moreover, these genetic variants affect the levels of serum unsaturated fatty acids and Δ desaturase indices, variables previously shown to correlate with obesity.
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| 2. |
- Leander, Mai, et al.
(författare)
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Impact of anxiety and depression on respiratory symptoms
- 2014
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 108:11, s. 1594-1600
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Tidskriftsartikel (refereegranskat)abstract
- Psychological factors such as anxiety and depression are prevalent in patients with asthma. The purpose of this study was to investigate the relationship between respiratory symptoms and psychological status and to estimate the importance of psychological status in comparison with other factors that are known to be associated with respiratory symptoms. This study included 2270 subjects aged 20-44 (52% female) from Sweden, Iceland, and Norway. Each participant underwent a clinical interview including questions on respiratory symptoms. Spirometry and methacholine challenge were performed. Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Eighty-two percent of the subjects reported no anxiety or depression whatsoever, 11% reported anxiety, 2.5% depression and 4% reported both anxiety and depression. All respiratory symptoms, such as wheezing, breathlessness and nightly symptoms, were more common, at a statistically significant level, in participants who had depression and anxiety, even after adjusting for confounders (ORs 1.33-1.94). The HADS score was the most important determinant for nightly symptoms and attacks of breathlessness when at rest whereas bronchial responsiveness was the most important determinant for wheezing, and breathlessness when wheezing. The probability of respiratory symptoms related to HADS score increased with increasing HADS score for all respiratory symptoms. In conclusion, there is a strong association between respiratory symptoms and psychological status. There is therefore a need for interventional studies designed to improve depression and anxiety in patients with respiratory symptoms. (C) 2014 Elsevier Ltd. All rights reserved.
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| 4. |
- Sällman Almén, Markus, et al.
(författare)
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Determination of the obesity-associated gene variants within the entire FTO gene by ultra-deep targeted sequencing in obese and lean children.
- 2013
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 37:3, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- Background:The Fat mass and obesity-associated gene (FTO) was the first gene reliably associated with body mass index in genome-wide association studies on a population level. At present, the genetic variations within the FTO gene are still the common variants that have the largest influence on body mass index.Methods:In the current study, we amplified the entire FTO gene, in total 412 Kbp, in over 200 long-range PCR fragments from each individual, from 524 severely obese and 527 lean Swedish children, and sequenced the products as two DNA pools using massive parallel sequencing (SOLiD).Results:The sequencing achieved very high coverage (median 18 000 reads) and we detected and estimated allele frequencies for 705 single nucleotide polymorphisms (SNPs) (19 novel) and 40 indels (24 novel) using a sophisticated statistical approach to remove false-positive SNPs. We identified 19 obesity-associated SNPs within intron one of the FTO gene, and validated our findings with genotyping. Ten of the validated obesity-associated SNPs have a stronger obesity association (P<0.007) than the commonly studied rs9939609 SNP (P<0.012).Conclusions:This study provides a comprehensive obesity-associated variation map of FTO, identifies novel lead SNPs and evaluates putative causative variants. We conclude that intron one is the only region within the FTO gene associated with obesity, and finally, we establish next generation sequencing of pooled DNA as a powerful method to investigate genetic association with complex diseases and traits.
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