| 81. |
- Dam, Veerle, et al.
(författare)
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Genetically Determined Reproductive Aging and Coronary Heart Disease : A Bidirectional 2-sample Mendelian Randomization
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:7, s. E2952-E2961
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause. Objectives: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men. Design: Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard inverse-variance weighted (IVW) regression, and MR-Egger regression. Participants: Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were pooled for the different analyses. Main Outcome Measures: CHD, CHD risk factors, and ANM. Results: Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in women (relative risk estimateIVW = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging. Conclusion: Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men.
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| 82. |
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| 83. |
- Dieden, A., et al.
(författare)
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Biomarkers associated with prevalent hypertension and higher blood pressure in a population-based cohort : a proteomic approach
- 2022
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 43:Suppl 2, s. 2189-2189
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundGlobally, hypertension represents an enormous health issue as it is a major, yet modifiable risk factor for developing cardiovascular disease. Recently, chitinase-3-like protein 1 (CHI3L1) was shown to be positively associated with the incidence of hypertension among prehypertensive subjects, and variants of CHI3L1 gene were associated with both CHI3L1-levels and hypertension.PurposeTo explore associations between prevalent hypertension and blood pressure, and 92 proteins with involvement in inflammation and cardiovascular disease.MethodsPlasma samples from 1713 individuals from a Swedish population-based cohort (mean age 67.3±6.0 years; 28.9% women) were analysed with a proximity extension assay panel, consisting of 92 proteins. Prior to all analyses, subjects with prevalent cardiovascular disease, defined as having a history of prevalent coronary or stroke event, were excluded (n=189). Univariate logistic regression models were carried out exploring associations between each of the 92 proteins and prevalent hypertension, defined as systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg, or use of antihypertensive treatment (n=1168, 76.4%). Bonferroni-corrected significant associations between proteins and hypertension were further analysed using stepwise selection of covariates, namely age, body mass index, diabetes status, and cystatin C, in logistic regression models. Proteins with significant adjusted associations with prevalent hypertension were further analysed for associations with systolic and diastolic blood pressure individually in stepwise linear regression models. Complete data on all variables were available in 1527 subjects.ResultsSixteen proteins were significantly associated with prevalent hypertension in univariate analyses. After adjustment, three proteins remained significantly associated with prevalent hypertension (i.e., CHI3L1, low-density lipoprotein receptor (LDL receptor) and tissue plasminogen activator (tPA); Table 1). In analyses of associations with systolic blood pressure, CHI3L1 and LDL receptor showed significant associations. In analyses of associations with diastolic blood pressure, CHI3L1, LDL receptor and tPA showed significant associations (Table 1).ConclusionsHigher CHI3L1, tPA and LDL receptor levels were positively associated with prevalent hypertension after multivariable adjustment, among 1527 elderly subjects without established cardiovascular disease. Furthermore, higher CHI3L and LDL receptor levels were positively associated with mean systolic, as well as mean diastolic blood pressure in multivariable analyses.Funding AcknowledgementType of funding sources: Foundation. Main funding source(s): The Swedish Medical Research Council and The Swedish Heart and Lung Foundation
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| 84. |
- Ding, Ming, et al.
(författare)
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Dairy consumption, systolic blood pressure, and risk of hypertension : Mendelian randomization study
- 2017
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833 .- 0959-8138. ; 356
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. DESIGN Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. SETTING CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. PARTICIPANTS Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis. MAIN OUTCOME MEASURES The instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. RESULTS Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (beta=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: beta=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). CONCLUSION The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.
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| 85. |
- Evangelou, Evangelos, et al.
(författare)
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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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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)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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| 86. |
- Fawad, A., et al.
(författare)
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The association between plasma proneurotensin and glucose regulation is modified by country of birth
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of type 2 diabetes (T2D) has increased dramatically in Middle Eastern populations that represent the largest non-European immigrant group in Sweden today. As proneurotensin predicts T2D, the aim of this study was to investigate differences in proneurotensin levels across populations of Middle Eastern and Caucasian origin and to study its associations with indices of glucose regulation. Participants in the age 30 to 75 years, living in Malmö, Sweden, and born in Iraq or Sweden, were recruited from the census register. Anthropometrics and fasting samples were collected and oral glucose tolerance tests conducted assessing insulin secretion (DIo) as well as insulin sensitivity (ISI). A total of 2155 individuals participated in the study, 1398 were Iraqi-born and 757 were Swedish-born participants. Higher fasting proneurotensin levels were observed in Iraqi- compared to Swedish-born participants (137.5 vs. 119.8 pmol/L; p < 0.001) data adjusted for age, sex and body mass index. In Iraqi participants only, plasma proneurotensin was associated with impaired glucose regulation assessed as ISI, DIo and HbA1c, and significant interactions between country of birth and proneurotensin were observed (Pinteraction ISI = 0.048; Pinteraction DIo = 0.014; PinteractionHbA1c = 0.029). We report higher levels of proneurotensin in the general Middle Eastern population. The finding that Middle Eastern origin modifies the relationship of proneurotensin with indices of glucose regulation suggests that proneurotensin may be a stronger determinant of T2D in Middle Eastern as compared to Caucasian populations. These findings may explain part of the excess T2D risk in the Middle Eastern population but needs to be explored further.
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| 87. |
- Fritzell, Emma, 1979, et al.
(författare)
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Drying kinetics and equilibrium moisture content of MDF fibres
- 2009
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Ingår i: Drying Technology. - : Informa UK Limited. - 1532-2300 .- 0737-3937. ; 27:9, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- An experimental device was constructed to study the drying kinetics of wood fibers under controlled conditions. The device consisted of a drying chamber in which a net basket filled with the fiber material was connected to a load cell. The drying medium was then forced through the basket at controlled levels of humidity and temperature. Experiments were performed with spruce fibers and the drying medium at varying temperature (50-170° C) and relative humidity (1-86%). In general, the drying rate increased with increasing temperature and decreasing relative humidity. A constant drying rate period was observed in all cases. The critical moisture content was approximately 1.25. The characteristic drying curve has a slight downward concave shape. The equilibrium moisture contents obtained at ambient temperature agree well with data in the literature. © 2009 Taylor & Francis Group, LLC.
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| 88. |
- Ganesh, Santhi K., et al.
(författare)
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Loci influencing blood pressure identified using a cardiovascular gene-centric array
- 2013
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:8, s. 1663-1678
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
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| 89. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 90. |
- Gaziano, Liam, et al.
(författare)
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Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
- 2022
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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