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| 2. |
- Grundberg, E, et al.
(författare)
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Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men
- 2007
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 19:6, s. 829-837
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Tidskriftsartikel (refereegranskat)abstract
- Summary Herein we investigated the association between polymorphisms in the LRP5 gene and bone phenotypes and fractures in three large male cohorts based on the rationale that mutations in LRP5 cause severe bone phenotypes. Results showed an association of the Val667Met SNP with spine BMD in 3,800 young and elderly men. Introduction The low-density lipoprotein receptor-related protein 5 (LRP5)-Wnt signalling system is of importance for regulating osteoblastic activity, which became clear after findings that inactivating mutations in LRP5 cause osteoporosis. The overall aim of this study was to investigate the association between polymorphisms in the LRP5 gene and bone mineral density (BMD) in three large cohorts of young and elderly men. Methods The cohorts used were MrOS Sweden (n = 3014, aged 69–81 years) and MrOs Hong Kong (n = 2000, aged > 65 years) and the Swedish GOOD study (n = 1068, aged 18–20 years). The polymorphisms Val667Met and Ala1330Val were genotyped using a TaqMan assay. Results When combining the data from the Swedish cohorts in a meta-analysis (n = 3,800), men carrying the 667Met-allele had 3% lower BMD at lumbar spine compared with non-carriers (p < 0.05). The Val667Met SNP was not polymorphic in the Hong Kong population and thus were not included. There were no associations between the Ala1330Val SNP and bone phenotypes in the study populations. No associations between the LRP5 polymorphisms and self-reported fractures were seen in MrOs Sweden. Conclusions Results from these three large cohorts indicate that the Val667Met polymorphism but not the Ala1330Val contributes to the observed variability in BMD in the Swedish populations.
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| 3. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 4. |
- Mootha, VK, et al.
(författare)
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PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.
- 2003
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 34:3, s. 267-273
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Tidskriftsartikel (refereegranskat)abstract
- DNA microarrays can be used to identify gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity. Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments.
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| 5. |
- Magnusson, Martin, et al.
(författare)
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Brain natriuretic peptide is related to diastolic dysfunction whereas urinary albumin excretion rate is related to left ventricular mass in asymptomatic type 2 diabetes patients
- 2010
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aims of this study were to estimate the prevalence of left ventricular systolic (LVSD) and diastolic (LVDD) dysfunction, and to test if BNP and urinary albumin excretion rate (AER) are related to LVSD, LVD and left ventricular mass (LVM) in asymptomatic type 2 diabetes patients. Methods: Presence of LVSD, LVDD and LVM, determined with echocardiography, was related to levels of BNP and AER in 153 consecutive asymptomatic patients with type 2 diabetes. Results: LVSD was present in 6.1% of patients whereas 49% (29% mild, 19% moderate and 0.7% severe) had LVDD and 9.4% had left ventricular hypertrophy. Increasing age (P < 0.0001) was the only independent variable related to mild LVDD whereas increasing BNP (P = 0.01), systolic blood pressure (P = 0.01), age (P = 0.003) and female gender (P = 0.04) were independent determinants of moderate to severe LVDD. AER (P = 0.003), age (P = 0.01) and male gender (P = 0.006) were directly and independently related to LVM. Conclusion: About half of asymptomatic type 2 diabetes patients have LVDD. Of those, more than one third display moderate LVDD pattern paralleled by increases in BNP, suggesting markedly increased risk of heart failure, especially in females, whereas AER and male sex are related to LVM.
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| 6. |
- Tornberg, Åsa, et al.
(författare)
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Relation between cycling exercise capacity, fiber-type composition, and lower extremity muscle strength and muscle endurance.
- 2011
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Ingår i: Journal of Strength and Conditioning Research. - 1533-4287. ; 25:1, s. 16-22
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Tidskriftsartikel (refereegranskat)abstract
- Segerström, ÅB, Holmbäck, AM, Hansson, O, Elgzyri, T, Eriksson, K-F, Ringsberg, K, Groop, L, Wollmer, P, and Thorsson, O. Relation between cycling exercise capacity, fiber-type composition, and lower extremity muscle strength and muscle endurance. J Strength Cond Res 25(1): 16-22, 2011-The aim of the study was to determine the relation between peak oxygen uptake (&OV0312;o2peak), peak work rate (WRpeak), fiber-type composition, and lower extremity strength and endurance during a maximal incremental cycle test. Thirty-nine healthy sedentary men, aged 30-46, participated in the study. Subjects performed a maximal incremental cycle test and isokinetic knee extension (KE) and flexion (KF) strength and endurance tests at velocities of 60 and 180°·s. Muscle biopsies were taken from m. vastus lateralis and analyzed for fiber-type composition. A significant correlation existed between KE strength and &OV0312;o2peak and WRpeak. Also, KF endurance correlated significantly to &OV0312;o2peak and WRpeak. The KE endurance correlated significantly to WRpeak (rp = 0.32, p < 0.05) and almost significantly to &OV0312;o2peak (rp = 0.28, p = 0.06). Stepwise multiple regression analyses showed that KE strength, KF endurance, and the percentage of type I fibers could explain up to 40% of the variation in &OV0312;o2peak and WRpeak. The performance of sedentary subjects in a maximal incremental cycle test is highly affected by knee muscle strength and endurance. Fiber-type composition also contributes but to a smaller extent.
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| 7. |
- Tornberg, Åsa, et al.
(författare)
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Upper Body Muscle Strength and Endurance in Relation to Peak Exercise Capacity During Cycling in Healthy Sedentary Male Subjects.
- 2011
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Ingår i: Journal of Strength and Conditioning Research. - 1533-4287. ; 25, s. 1413-1417
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Tidskriftsartikel (refereegranskat)abstract
- Segerström, AB, Holmbäck, AM, Elzyri, T, Eriksson, KF, Ringsberg, K, Groop, L, Thorsson, O, and Wollmer, P. Upper body muscle strength and endurance in relation to peak exercise capacity during cycling in healthy sedentary male subjects. J Strength Cond Res 24(x): 000-000, 2010-The aim of this study was to investigate the relation between upper body muscle strength and endurance, and exercise capacity during an incremental cycle exercise test in sedentary healthy male subjects before and after 6 months of combined supervised group training. Exercise capacity was measured as maximal oxygen consumption (&OV0312;O2peak) and maximum work rate (WRpeak). Muscle strength and endurance of the upper body were assessed by bench press and isometric measurement of trunk extensor and flexor maximum voluntary contraction (MVC) and trunk extensor and flexor endurance. Thirty-one subjects were studied before and after the training period. Bench press and trunk extensor MVC correlated to exercise capacity at baseline and after training. Training improved &OV0312;O2peak and WRpeak. The correlation between trunk extensor MVC and exercise capacity improved after training. Upper body strength may affect exercise capacity by increasing the rider's ability to generate force on the handlebar that can be transmitted to the pedals. Resistance training of the arms, chest, and trunk may help improve cycling performance.
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| 8. |
- Saxena, Richa, et al.
(författare)
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Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:2, s. 142-148
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Tidskriftsartikel (refereegranskat)abstract
- Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958–30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 10−10) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09–1.15, P = 4.8 × 10−18).
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| 9. |
- Voight, Benjamin F., et al.
(författare)
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Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:7, s. 579-589
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Tidskriftsartikel (refereegranskat)abstract
- By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
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| 10. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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