| 1. |
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| 2. |
- Sliz, E., et al.
(author)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 3. |
- Graff, M., et al.
(author)
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Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults
- 2017
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In: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:4
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Journal article (peer-reviewed)abstract
- Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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| 4. |
- Tabassum, R, et al.
(author)
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Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
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Journal article (peer-reviewed)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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| 5. |
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| 6. |
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| 7. |
- Locke, Adam E, et al.
(author)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Journal article (peer-reviewed)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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| 8. |
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| 9. |
- Kurki, MI, et al.
(author)
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FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
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Journal article (peer-reviewed)abstract
- Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Ried, Janina S., et al.
(author)
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)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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| 15. |
- Berndt, Sonja I., et al.
(author)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Journal article (peer-reviewed)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 16. |
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| 17. |
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| 18. |
- Evangelou, Evangelos, et al.
(author)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Journal article (peer-reviewed)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 19. |
- Lu, Yingchang, et al.
(author)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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| 20. |
- Kilpeläinen, Tuomas O, et al.
(author)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 21. |
- Wain, Louise V., et al.
(author)
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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
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In: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
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Journal article (peer-reviewed)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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| 22. |
- Dastani, Zari, et al.
(author)
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Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals
- 2012
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In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002607-
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Journal article (peer-reviewed)abstract
- Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P=4.5 x 10(-8)-1.2 x 10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3 x 10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p=4.3 x 10(-3), n = 22,044), increased triglycerides (p=2.6 x 10(-14), n = 93,440), increased waist-to-hip ratio (p=1.8 x 10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p=4.4 x 10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p=4.5x10(-13), n = 96,748) and decreased BMI (p= 1.4 x 10(-14), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
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| 23. |
- Hartman, Henrik, et al.
(author)
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Negative ion relaxation and reactions in a cryogenic storage ring
- 2020
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In: Journal of Physics: Conference Series Vol 1412. - : IOP Publishing. - 1742-6588 .- 1742-6596.
-
Conference paper (peer-reviewed)abstract
- An overview of recent experimental results of studies of negative atomic and molecular ions in the Double ElectroStatic Ion-Ring ExpEriment, DESIREE is given. Metastable level lifetimes in atomic negative ions have been measured by time-dependent laser photodetachment. Rotational relaxation of diatomic anions is studied by near-threshold photodetachment. Spontaneous decays of small metal cluster anions by electron emission and fragmentation is studied with decay-channel specificity. Finally, mutual neutralisation of pairs of negative and positive ions has been investigated with initial and final state selectivity.
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| 24. |
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| 25. |
- Qi, Qibin, et al.
(author)
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FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
-
Journal article (peer-reviewed)abstract
- FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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| 26. |
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| 27. |
- Chartkunchand, K. C., et al.
(author)
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Lifetimes of bound excited states of Pt-
- 2017
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In: Journal of Physics: Conference Series, Vol. 875, no. 022051. - : IOP Publishing. - 1742-6588.
-
Conference paper (peer-reviewed)abstract
- Measurements of the radiative lifetimes of the two excited states of the platinum anion Pt- are presented. Pt- ions stored in the cryogenic ion storage ring DESIREE were photodetached at different photon wavelengths and the resulting yield of neutral Pt measured as a function of time was recorded. Analysis of the neutral decay curves show a 2.54 +/- 0.10 s lifetime for the higher-lying 5d(10)6(s) S-2(1/2) excited state and a lifetime in the range of 50-200 ms for the lower- lying 5d(9)6(s)(2) D-2(3/2) excited state. This is the first study to report the lifetime of a bound anion excited state with an electron configuration different from that of the anion ground state.
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| 28. |
- Rofors, E., et al.
(author)
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Response of a Li-glass/multi-anode photomultiplier detector to focused proton and deuteron beams
- 2020
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 984
-
Journal article (peer-reviewed)abstract
- The response of a position-sensitive Li-glass based scintillation detector being developed for thermal-neutron detection with 6 mm position resolution has been investigated using focused beams of 2.5MeV protons and deuterons. The beams were scanned across the detector in 0.5 mm horizontal and vertical steps perpendicular to the beams. Scintillation light was registered using an 8 × 8 pixel multi-anode photomultiplier tube. The signal amplitudes were recorded for each pixel on an event-by-event basis. Several pixels generally registered considerable signals at each beam location. To optimize planned detector operation at the European Spallation Source, the number of pixels above set thresholds was investigated, with the maximization of the single-hit efficiency over the largest possible area as the primary goal. For both beams, at a threshold of ∼50% of the mean of the full-deposition peak, ∼80% of the events were registered in a single pixel, resulting in an effective position resolution of ∼5 mm in X and Y. Lower thresholds resulted in higher pixel multiplicities. These events could also be localized with the same effective position resolution.
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| 29. |
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| 30. |
- Fall, Tove, et al.
(author)
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Age- and sex-specific causal effects of adiposity on cardiovascular risk factors
- 2015
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 64:5, s. 1841-1852
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Journal article (peer-reviewed)abstract
- Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.
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| 31. |
- Najeeb, P. K., et al.
(author)
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Spontaneous decay of small carbon cluster dianions C-n(2-) (n=7-11)
- 2020
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In: Journal of Physics, Conference Series, Vol 1412, Article 232014. - : IOP Publishing. - 1742-6588 .- 1742-6596.
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Conference paper (peer-reviewed)abstract
- We have studied the stabilities of small carbon dianion clusters, C-n(2-) (n=7-11) in the cryogenic electrostatic ion storage ring, DESIREE. We observe spontaneous electron emission for tens of milliseconds, where dianions containing an even number of carbons decay slower in comparison to their neighbouring cluster sizes. For all the systems considered here, we find that there is a component which is stable at least on the time scales of hundreds of milliseconds.
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| 32. |
- Auro, K., et al.
(author)
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USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study
- 2008
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:3, s. 464-472
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Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: Genetic variants of upstream transcription factor 1 (USF1) have previously been associated with dyslipidaemias in family studies. Our aim was to further address the role of USF1 in metabolic syndrome and cardiovascular traits at the population level in a large Swedish male cohort (n=2,322) with multiple measurements for risk factors during 32 years of follow-up. METHODS: Participants, born in 1920-1924, were examined at 50, 60, 70 and 77 years of age. The follow-up period for cardiovascular events was 1970-2002. We genotyped three haplotype tagging polymorphisms capturing the major allelic variants of USF1. RESULTS: SNP rs2774279 was associated with the metabolic syndrome. The minor allele of rs2774279 was less common among individuals with metabolic syndrome than among healthy controls [p=0.0029 when metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III; p=0.0073 when defined according to the International Diabetes Federation (IDF)]. The minor allele of rs2774279 was also associated with lower BMI, lower fasting glucose values and higher HDL-cholesterol concentrations in longitudinal analyses. With SNP rs2073658, a borderline association with metabolic syndrome was observed (p=0.036, IDF), the minor allele being the risk-increasing allele. The minor allele of rs2073658 also associated with higher total and LDL-cholesterol, apolipoprotein B-100 and lipoprotein(a) concentrations in longitudinal analyses. Importantly, these trends with respect to the allelic variants prevailed throughout the follow-up time of three decades. CONCLUSIONS/INTERPRETATION: Our results suggest that USF1 variants associate with the metabolic syndrome at population level and influence the cardiovascular risk factors throughout adulthood in a consistent, longitudinal manner.
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| 33. |
- Hägg, Sara, et al.
(author)
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Adiposity as a cause of cardiovascular disease : a Mendelian randomization study
- 2015
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 44:2, s. 578-586
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Journal article (peer-reviewed)abstract
- Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods. Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes. Results: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12-1.28, P = 1.9.10(-7)), heart failure (HR = 1.47, 95% CI, 1.35-1.60, P = 9.10(-19)) and ischaemic stroke (HR = 1.15, 95% CI, 1.06-1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (beta = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028-0.033, P = 3.10(-107)). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12-3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05-3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD. Conclusions: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.
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| 34. |
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| 35. |
- Kristiansson, P., et al.
(author)
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Optical dot gain on newsprint determined with the Lund nuclear microprobe
- 1997
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In: Nuclear Instruments and Methods in Physics Research Section B. - Amsterdam : Elsevier. - 0168-583X .- 1872-9584. ; 130:1-4, s. 303-307
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Journal article (peer-reviewed)abstract
- A technique for measuring optical dot gain, i.e. the relative difference between the actual screen dot and the optically perceived one, is presented. By combining measurements from the non-optical nuclear microprobe with data from image analyzing technique the optical dot gain can be determined. The procedure to reach pixel by pixel correlation on a micrometer scale is discussed. In the newsprint sample studied in this investigation a typical optical dot gain between 15 and 20% was deduced. The variation in the optical dot gain was correlated with other characteristic parameters of the print and newsprint and especially a positive correlation to the mass density of the newsprint was observed. (C) 1997 Elsevier Science Ltd.
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| 36. |
- Lilja, Mikael, et al.
(author)
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Determinants of HbA1c in patients with type 1 diabetes in seven Swedish county councils
- 2015
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In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 58:Suppl. 1 Abstr. 278, s. S140-S141
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Journal article (other academic/artistic)abstract
- Background and aims: In order to make fair comparisons between the results of different health care providers, proper consideration of the casemix of the populations they serve is important. HbA1c is often used as a metric to indicate the quality of diabetes care, it is therefore of value to determine what patient characteristics affect this outcome. As part of the ongoing National Collaboration for Value Based Reimbursement and Monitoring Systems, we therefore set out to investigate what factors are associated with HbA1c in a large retrospective cohort of persons with type 1 diabetes.Materials and methods: This was a retrospective register study where we analyzed persons 18 years or older, with a health care contact and a diagnosis of diabetes during 2010-11 in the administrative systems of seven Swedish county councils (Dalarna, Jämtland Härjedalen, Skåne, Stockholm, Uppsala, Västra Götaland and Östergötland), covering ~70% of the Swedish population and linked this data to data from the National Diabetes Register, socioeconomic data from Statistics Sweden and data on filled prescriptions from the Prescribed Drug Register. We estimated a random effect model on HbA1c after one year of follow-up, including socioeconomic, demographic and clinical factors.Results: Based on a complete case approach, 13 396 patients were analyzed. Women had on average higher HbA1c than men. Blood sugar control seemed to be better with higher age. Of the socioeconomic factors, higher education was associated with lower levels of HbA1c, as was being married. By contrast, we found no association between HbA1c and being born outside the EU.Ahistory (previous 2 years) of diabetes related complications were associated with higher levels of HbA1c, which is likely due to high levels of HbA1c being an indicator of what is causing the complications in the first place. The exception to this pattern was patients with renal failure.Conclusion: Apart from obvious demographic factors such as age and gender as well as disease history, educational and civil status are important factors to take into consideration when comparing obtained HbA1c levels between health care providers. This also raises the question of the need for additional focus on education directed towards these groups to facilitate improved diabetes management.
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- Frost, R. J. W., et al.
(author)
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A compact accelerator driven neutron source at the Applied Nuclear Physics Laboratory, Lund University
- 2023
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In: EPJ TECHNIQUES AND INSTRUMENTATION. - : Springer Nature. - 2195-7045. ; 10:1
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Journal article (peer-reviewed)abstract
- The Applied Nuclear Physics Group at Lund University has constructed a CANS (Compact Accelerator-driven Neutron Source). The CANS is based around a 3 MV, single-ended, Pelletron accelerator, which is used to impinge a 2.8 MeV deuterium beam into a beryllium target. The anticipated neutron production will be on the order of 10(10) n/s in 4 pi sr, with future upgrades expected to increase neutron production to 10(11) n/s. Neutron energy will be up to 9 MeV with peak emission at similar to 5 MeV. Shielding and moderation will be provided by a large water tank surrounding the target, with exit ports to allow moderated neutrons to be directed to experiments. The thermal-neutron flux at the exit of the extraction ports is anticipated to be up to 10(6) n/cm(2)/s. The CANS will be used to forward the activities of the group in the area of neutron-activation analysis, in addition to a broader range of neutron related applications.
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| 43. |
- Malmqvist, K. G., et al.
(author)
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PIXE and proton microprobe advances at the Lund Institute of Technology
- 1989
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In: Nuclear Inst. and Methods in Physics Research, B. - 0168-583X. ; 40-41:PART 1, s. 685-689
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Journal article (peer-reviewed)abstract
- A review of recent advances in high-energy ion beam analysis at the Lund Institute of Technology is presented. A nonvacuum specimen chamber allows chemical speciation using a combination of ion beam analysis and controlled heating. The development of a new versatile scanning proton microbeam based on a new dedicated accelerator, an achromatic triplet lens and an advanced specimen chamber is outlined together with the performance of a microVAX-II/VMEbus-based data acquisition system.
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| 44. |
- Moberg, T, et al.
(author)
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CSF 5-HIAA and exposure to and expression of interpersonal violence in suicide attempters
- 2011
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In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 132:1-2, s. 173-178
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Journal article (peer-reviewed)abstract
- BACKGROUND: Serotonin is implicated in impaired impulse control, aggression and suicidal behaviour. Low cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been found in violent suicide attempters, suicide victims and in violent offenders. CSF 5-HIAA concentrations have both genetic and environmental determinants. Childhood trauma may have an effect on central monoamine function as an adult.AIM: The aim of this study was to assess the relationship of CSF 5-HIAA and the exposure to and the expression of violence in childhood and during adult life measured with the Karolinska Interpersonal Violence Scale (KIVS).METHOD: 42 medication free suicide attempters underwent lumbar puncture and were assessed with the Karolinska Interpersonal Violence Scale (KIVS) to assess history of childhood exposure to violence and lifetime expressed violent behaviour.RESULTS: In women, but not in men, CSF 5-HIAA showed a significant negative correlation to exposure to violence during childhood. Furthermore, suicide attempters with low CSF 5-HIAA were more prone to commit violent acts as an adult if exposed to violence as a child compared to suicide attempters with high CSF 5-HIAA. In the non-traumatized group, CSF 5-HIAA showed a significant negative correlation to expressed violent behaviour in childhood.CONCLUSIONS: Although central serotonergic function has important genetic determinants, exposure to childhood trauma may also affect serotonergic function. Low serotonergic function may facilitate impaired aggression control in traumatized suicide attempters.
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| 45. |
- Nettleton, Jennifer A, et al.
(author)
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Gene x dietary pattern interactions in obesity : analysis of up to 68 317 adults of European ancestry
- 2015
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 24:16, s. 4728-4738
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Journal article (peer-reviewed)abstract
- Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.
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| 48. |
- Bartek, J., et al.
(author)
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Clinical Course in Chronic Subdural Hematoma Patients Aged 18-49 Compared to Patients 50 Years and Above: A Multicenter Study and Meta-Analysis
- 2019
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In: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 10
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Journal article (peer-reviewed)abstract
- Objective: Chronic Subdural Hematoma (cSDH) is primarily a disease of elderly, and is rare in patients < 50 years, and this may in part be related to the increased brain atrophy from 50 years of age. This fact may also influence clinical presentation and outcome. The aim of this study was to study the clinical course with emphasis on clinical presentation of cSDH patients in the young (<50 years). Methods: A retrospective review of a population-based cohort of 1,252 patients operated for cSDH from three Scandinavian neurosurgical centers was conducted. The primary end-point was difference in clinical presentation between the patients <50 y/o and the remaining patients (>= 50 y/o group). The secondary end-points were differences in perioperative morbidity, recurrence and mortality between the two groups. In addition, a meta-analysis was performed comparing clinical patterns of cSDH in the two age groups. Results: Fifty-two patients (4.2%) were younger than 50 years. Younger patients were more likely to present with headache (86.5% vs. 37.9%, p < 0.001) and vomiting (25% vs. 5.2%, p < 0.001) than the patients >= 50 y/o, while the >= 50 y/o group more often presented with limb weakness (17.3% vs. 44.8%, p < 0.001), speech impairment (5.8% vs. 26.2%, p = 0.001) and gait disturbance or falls (23.1% vs. 50.7%, p < 0.001). There was no difference between the two groups in recurrence, overall complication rate and mortality within 90 days. Our meta-analysis confirmed that younger patients are more likely to present with headache (p = 0.015) while the hemispheric symptoms are more likely in patients >= 50 y/o (p < 0.001). Conclusion: Younger patients with cSDH present more often with signs of increased intracranial pressure, while those >= 50 y/o more often present with hemispheric symptoms. No difference exists between the two groups in terms of recurrence, morbidity, and short-term mortality. Knowledge of variations in clinical presentation is important for correct and timely diagnosis in younger cSDH patients.
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| 49. |
- Bartek, J, et al.
(author)
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Surgery for chronic subdural hematoma in nonagenarians: A Scandinavian population-based multicenter study.
- 2017
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In: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 136:5, s. 516-520
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Journal article (peer-reviewed)abstract
- Chronic subdural hematoma (cSDH) is a prevalent condition often seen in the elderly, with surgery being the treatment of choice when symptomatic. So far, few have explored the surgical outcomes in patients 90years or older. The aim of this study was to investigate outcome after cSDH surgery in nonagenarians (≥90 y/o group) compared to younger adult patients (<90 y/o group).In a Scandinavian population-based cohort we conducted a retrospective review of 1,254 patients undergoing primary burr-hole procedures for cSDH between January 1, 2005 and December 31, 2010 at three neurosurgical centers. In a comparative analysis, the primary end-point was difference in hematoma recurrence rates between the ≥90 y/o and <90 y/o groups. The secondary end-points were differences in perioperative morbidity and mortality between groups.75 patients were 90years or older. There was no significant difference in recurrences resulting in reoperation between the age groups (10.7% vs 13.6%, P=.47). There was also no significant difference in overall complication rate (4.1% vs 8.1%, P=.21) or severe complications (1.4% vs 2.0%, P=.68). There were three (4.0%) perioperative deaths within 30days in the ≥90 y/o group and 40 (3.4%) in the <90 y/o group (P=.78).Patients 90years or older had similar rates of recurrence, perioperative morbidity and perioperative mortality as compared to younger patients. Age alone should not be a contraindication for surgery in patients with cSDH.
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