| 51. |
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| 52. |
- Kornfeld, Jan-Wilhelm, et al.
(författare)
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Variants in STAT5B Associate with Serum TC and LDL-C Levels
- 2011
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 96:9, s. E1496-E1501
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Tidskriftsartikel (refereegranskat)abstract
- Context: Known genetic variants influencing serum lipid levels do not adequately account for the observed population variability of these phenotypes. The GH/signal transducers and activators of transcription (STAT) signaling pathway is an evolutionary conserved system that exerts strong effects on metabolism, including that of lipids. Research Design and Methods: We analyzed the association of 11 single-nucleotide polymorphisms (SNP) spanning the STAT5B/STAT5A/STAT3 locus with serum lipid levels in six European populations (n = 5162 nondiabetic individuals). Results: After adjustment for age, sex, alcohol use, smoking, and body mass index, we identified STAT5B variants(rs8082391 and rs8064638) in novel association with total cholesterol (TC; P = 0.001 and P = 0.002) and low-density lipoprotein cholesterol (P = 0.002 and P = 0.004) levels. The minor alleles of these single-nucleotide polymorphisms were significantly enriched in hyperlipidemic individuals across the six discovery populations (P = 0.004 and P = 0.006). In transgenic mice deficient for hepatic STAT5A and STAT5B, reduced serum TC levels coincided with reduced hepatic cholesterol biosynthesis as demonstrated using gene expression profiling and pathway enrichment analysis. Conclusions: Genetic variants in STAT5B are associated with TC and low-density lipoprotein cholesterol levels among six populations. Mechanistically, STAT5B transcriptionally regulates hepatic cholesterol homeostasis.
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| 53. |
- Marroni, Fabio, et al.
(författare)
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A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations : the EUROSPAN project
- 2009
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-3268. ; 2:4, s. 322-328
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We set out to identify common genetic determinants of the length of the RR and QT intervals in 2325 individuals from isolated European populations. METHODS AND RESULTS: We analyzed the heart rate at rest, measured as the RR interval, and the length of the corrected QT interval for association with 318 237 single-nucleotide polymorphisms. The RR interval was associated with common variants within GPR133, a G-protein-coupled receptor (rs885389, P=3.9 x 10(-8)). The QT interval was associated with the earlier reported NOS1AP gene (rs2880058, P=2.00 x 10(-10)) and with a region on chromosome 13 (rs2478333, P=4.34 x 10(-8)), which is 100 kb from the closest known transcript LOC730174 and has previously not been associated with the length of the QT interval. CONCLUSIONS: Our results suggested an association between the RR interval and GPR133 and confirmed an association between the QT interval and NOS1AP.
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| 54. |
- Pattaro, Cristian, et al.
(författare)
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Genome-wide linkage analysis of serum creatinine in three isolated European populations
- 2009
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 76:3, s. 297-306
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing evidence for a role of genetic predisposition in the etiology of kidney disease, but linkage scans have been poorly replicated. Here we performed a genome-wide linkage analysis of serum creatinine on 2859 individuals from isolated villages in South Tyrol (Italy), Rucphen (The Netherlands) and Vis Island (Croatia), populations that have been stable and permanently resident in their region. Linkage of serum creatinine levels to loci on chromosomes 7p14, 9p21, 11p15, 15q15-21, 16p13, and 18p11 was successfully replicated in at least one discovery population or in the pooled analysis. A novel locus was found on chromosome 10p11. Linkage to chromosome 22q13, independent of diabetes and hypertension, was detected over a region containing the non-muscle myosin heavy chain type II isoform A (MYH9) gene (LOD score=3.52). In non-diabetic individuals, serum creatinine was associated with this gene in two of the three populations and in meta-analysis (SNP rs11089788, P-value=0.0089). In populations sharing a homogeneous environment and genetic background, heritability of serum creatinine was higher than in outbred populations, with consequent detection of a larger number of loci than reported before. Our finding of a replicated association of serum creatinine with the MYH9 gene, recently linked to pathological renal conditions in African Americans, suggests that this gene may also influence kidney function in healthy Europeans.
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| 55. |
- Huffman, Jennifer E., et al.
(författare)
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Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, P-inter= 2.6 x 10(-8)). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDAR-ADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10(-8)), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10(-8)), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10(-4)). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.
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| 56. |
- Jerzembeck, Fabian, et al.
(författare)
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The superconductivity of Sr2RuO4 under c-axis uniaxial stress
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Applying in-plane uniaxial pressure to strongly correlated low-dimensional systems has been shown to tune the electronic structure dramatically. For example, the unconventional superconductor Sr2RuO4 can be tuned through a single Van Hove point, resulting in strong enhancement of both T-c and H-c2. Out-of-plane (c axis) uniaxial pressure is expected to tune the quasi-two-dimensional structure even more strongly, by pushing it towards two Van Hove points simultaneously. Here, we achieve a record uniaxial stress of 3.2 GPa along the c axis of Sr2RuO4. H-c2 increases, as expected for increasing density of states, but unexpectedly T-c falls. As a first attempt to explain this result, we present three-dimensional calculations in the weak interaction limit. We find that within the weak-coupling framework there is no single order parameter that can account for the contrasting effects of in-plane versus c-axis uniaxial stress, which makes this new result a strong constraint on theories of the superconductivity of Sr2RuO4. In the superconductor Sr2RuO4, in-plane strain is known to enhance both the superconducting transition temperature Tc and upper critical field Hc2, but the effect of out-of-plane strain has not been studied. Here, the authors find that Hc2 is enhanced under out-of-plane strain, but Tc unexpectedly decreases.
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| 57. |
- Kwan, Johnny S H, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels.
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6684-93
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Tidskriftsartikel (refereegranskat)abstract
- Osteoprotegerin (OPG) is involved in bone homeostasis and tumor cell survival. Circulating OPG levels are also important biomarkers of various clinical traits, such as cancers and atherosclerosis. OPG levels were measured in serum or in plasma. In a meta-analysis of genome-wide association studies in up to 10,336 individuals from European and Asian origin, we discovered that variants >100 Kb upstream of the TNFRSF11B gene encoding OPG and another new locus on chromosome 17q11.2 were significantly associated with OPG variation. We also identified a suggestive locus on chromosome 14q21.2 associated with the trait. Moreover, we estimated that over half of the heritability of OPG levels could be explained by all variants examined in our study. Our findings provide further insight into the genetic regulation of circulating OPG levels.
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| 58. |
- Liu, Jun, et al.
(författare)
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A multi-omics study of circulating phospholipid markers of blood pressure
- 2022
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Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- High-throughput techniques allow us to measure a wide-range of phospholipids which can provide insight into the mechanisms of hypertension. We aimed to conduct an in-depth multi-omics study of various phospholipids with systolic blood pressure (SBP) and diastolic blood pressure (DBP). The associations of blood pressure and 151 plasma phospholipids measured by electrospray ionization tandem mass spectrometry were performed by linear regression in five European cohorts (n = 2786 in discovery and n = 1185 in replication). We further explored the blood pressure-related phospholipids in Erasmus Rucphen Family (ERF) study by associating them with multiple cardiometabolic traits (linear regression) and predicting incident hypertension (Cox regression). Mendelian Randomization (MR) and phenome-wide association study (Phewas) were also explored to further investigate these association results. We identified six phosphatidylethanolamines (PE 38:3, PE 38:4, PE 38:6, PE 40:4, PE 40:5 and PE 40:6) and two phosphatidylcholines (PC 32:1 and PC 40:5) which together predicted incident hypertension with an area under the ROC curve (AUC) of 0.61. The identified eight phospholipids are strongly associated with triglycerides, obesity related traits (e.g. waist, waist-hip ratio, total fat percentage, body mass index, lipid-lowering medication, and leptin), diabetes related traits (e.g. glucose, insulin resistance and insulin) and prevalent type 2 diabetes. The genetic determinants of these phospholipids also associated with many lipoproteins, heart rate, pulse rate and blood cell counts. No significant association was identified by bi-directional MR approach. We identified eight blood pressure-related circulating phospholipids that have a predictive value for incident hypertension. Our cross-omics analyses show that phospholipid metabolites in the circulation may yield insight into blood pressure regulation and raise a number of testable hypothesis for future research.
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| 59. |
- Love, David C., et al.
(författare)
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Emerging COVID-19 impacts, responses, and lessons for building resilience in the seafood system
- 2021
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Ingår i: Global food security. - : Elsevier BV. - 2211-9124. ; 28
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic and subsequent lockdowns are creating health and economic crises that threaten food and nutrition security. The seafood sector provides important sources of nutrition and employment, especially in low-income countries, and is highly globalized allowing shocks to propagate. We studied COVID-19-related disruptions, impacts, and responses to the seafood sector from January through May 2020, using a food system resilience ‘action cycle’ framework as a guide. We find that some supply chains, market segments, companies, small-scale actors and civil society have shown initial signs of greater resilience than others. COVID-19 has also highlighted the vulnerability of certain groups working in- or dependent on the seafood sector. We discuss early coping and adaptive responses combined with lessons from past shocks that could be considered when building resilience in the sector. We end with strategic research needs to support learning from COVID-19 impacts and responses.
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| 60. |
- Mascalzoni, Deborah, 1973-, et al.
(författare)
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Balancing scientific interests and the rights of participants in designing a recall by genotype study
- 2021
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Ingår i: European Journal of Human Genetics. - : Springer Nature. - 1018-4813 .- 1476-5438. ; 29:7, s. 1146-1157
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Tidskriftsartikel (refereegranskat)abstract
- Recall by genotype (RbG) studies aim to better understand the phenotypes that correspond to genetic variants of interest, by recruiting carriers of such variants for further phenotyping. RbG approaches pose major ethical and legal challenges related to the disclosure of possibly unwanted genetic information. The Cooperative Health Research in South Tyrol (CHRIS) study is a longitudinal cohort study based in South Tyrol, Italy. Demand has grown for CHRIS study participants to be enrolled in RbG studies, thus making the design of a suitable ethical framework a pressing need. We here report upon the design of a pilot RbG study conducted with CHRIS study participants. By reviewing the literature and by consulting relevant stakeholders (CHRIS participants, clinical geneticists, ethics board, GPs), we identified key ethical issues in RbG approaches (e.g. complexity of the context, communication of genetic results, measures to further protect participants). The design of the pilot was based on a feasibility assessment, the selection of a suitable test case within the ProtectMove Research Unit on reduced penetrance of hereditary movement disorders, and the development of appropriate recruitment and communication strategies. An empirical study was embedded in the pilot study with the aim of understanding participants' views on RbG. Our experience with the pilot study in CHRIS allowed us to contribute to the development of best practices and policies for RbG studies by drawing recommendations: addressing the possibility of RbG in the original consent, implementing tailored communication strategies, engaging stakeholders, designing embedded empirical studies, and sharing research experiences and methodology.
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