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Sökning: WFRF:(Ploner Alexander)

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1.
  • Fall, Tove, et al. (författare)
  • The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis
  • 2013
  • Ingår i: PLoS Medicine. - : Public Library of Science. - 1549-1676 .- 1549-1277. ; 10:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
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2.
  • Christensen, S. E., et al. (författare)
  • Relative Validity of Micronutrient and Fiber Intake Assessed With Two New Interactive Meal- and Web-Based Food Frequency Questionnaires
  • 2014
  • Ingår i: Journal of Medical Internet Research. - : JMIR PUBLICATIONS, INC. - 1438-8871. ; 16:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The meal-and Web-based food frequency questionnaires, Meal-Q and MiniMeal-Q, were developed for cost-efficient assessment of dietary intake in epidemiological studies. Objective: The objective of this study was to evaluate the relative validity of micronutrient and fiber intake assessed with Meal-Q and MiniMeal-Q. The reproducibility of Meal-Q was also evaluated. Methods: A total of 163 volunteer men and women aged between 20 and 63 years were recruited from Stockholm County, Sweden. Assessment of micronutrient and fiber intake with the 174-item Meal-Q was compared to a Web-based 7-day weighed food record (WFR). Two administered Meal-Q questionnaires were compared for reproducibility. The 126-item MiniMeal-Q, developed after the validation study, was evaluated in a simulated validation by using truncated Meal-Q data. Results: The study population consisted of approximately 80% women (129/163) with a mean age of 33 years (SD 12) who were highly educated (130/163, 80% with >12 years of education) on average. Cross-classification of quartiles with the WFR placed 69% to 90% in the same/adjacent quartile for Meal-Q and 67% to 89% for MiniMeal-Q. Bland-Altman plots with the WFR and the questionnaires showed large variances and a trend of increasing underestimation with increasing intakes. Deattenuated and energy-adjusted Spearman rank correlations between the questionnaires and the WFR were in the range rho=.25-.69, excluding sodium that was not statistically significant. Cross-classifications of quartiles of the 2 Meal-Q administrations placed 86% to 97% in the same/adjacent quartile. Intraclass correlation coefficients for energy-adjusted intakes were in the range of .50-.76. Conclusions: With the exception of sodium, this validation study demonstrates Meal-Q and MiniMeal-Q to be useful methods for ranking micronutrient and fiber intake in epidemiological studies with Web-based data collection.
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3.
  • Christensen, S. E., et al. (författare)
  • Two New Meal- and Web-Based Interactive Food Frequency Questionnaires: Validation of Energy and Macronutrient Intake
  • 2013
  • Ingår i: Journal of Medical Internet Research. - : JMIR PUBLICATIONS, INC. - 1438-8871. ; 15:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Meal-Q and its shorter version, MiniMeal-Q, are 2 new Web-based food frequency questionnaires. Their meal-based and interactive format was designed to promote ease of use and to minimize answering time, desirable improvements in large epidemiological studies. Objective: We evaluated the validity of energy and macronutrient intake assessed with Meal-Q and MiniMeal-Q as well as the reproducibility of Meal-Q. Methods: Healthy volunteers aged 20-63 years recruited from Stockholm County filled out the 174-item Meal-Q. The questionnaire was compared to 7-day weighed food records (WFR; n=163), for energy and macronutrient intake, and to doubly labeled water (DLW; n=39), for total energy expenditure. In addition, the 126-item MiniMeal-Q was evaluated in a simulated validation using truncated Meal-Q data. We also assessed the answering time and ease of use of both questionnaires. Results: Bland-Altman plots showed a varying bias within the intake range for all validity comparisons. Cross-classification of quartiles placed 70%-86% in the same/adjacent quartile with WFR and 77% with DLW. Deattenuated and energy-adjusted Pearson correlation coefficients with the WFR ranged from r=0.33-0.74 for macronutrients and was r=0.18 for energy. Correlations with DLW were r=0.42 for Meal-Q and r=0.38 for MiniMeal-Q. Intraclass correlations for Meal-Q ranged from r=0.57-0.90. Median answering time was 17 minutes for Meal-Q and 7 minutes for MiniMeal-Q, and participants rated both questionnaires as easy to use. Conclusions: Meal-Q and MiniMeal-Q are easy to use and have short answering times. The ranking agreement is good for most of the nutrients for both questionnaires and Meal-Q shows fair reproducibility.
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4.
  • Almqvist, C, et al. (författare)
  • LifeGene-a large prospective population-based study of global relevance
  • 2011
  • Ingår i: European Journal of Epidemiology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0393-2990 .- 1573-7284. ; 26:1, s. 67-77
  • Tidskriftsartikel (refereegranskat)abstract
    • Studying gene-environment interactions requires that the amount and quality of the lifestyle data is comparable to what is available for the corresponding genomic data. Sweden has several crucial prerequisites for comprehensive longitudinal biomedical research, such as the personal identity number, the universally available national health care system, continuously updated population and health registries and a scientifically motivated population. LifeGene builds on these strengths to bridge the gap between basic research and clinical applications with particular attention to populations, through a unique design in a research-friendly setting. LifeGene is designed both as a prospective cohort study and an infrastructure with repeated contacts of study participants approximately every 5 years. Index persons aged 18-45 years old will be recruited and invited to include their household members (partner and any children). A comprehensive questionnaire addressing cutting-edge research questions will be administered through the web with short follow-ups annually. Biosamples and physical measurements will also be collected at baseline, and re-administered every 5 years thereafter. Event-based sampling will be a key feature of LifeGene. The household-based design will give the opportunity to involve young couples prior to and during pregnancy, allowing for the first study of children born into cohort with complete pre-and perinatal data from both the mother and father. Questions and sampling schemes will be tailored to the participants' age and life events. The target of LifeGene is to enrol 500,000 Swedes and follow them longitudinally for at least 20 years.
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5.
  • Dahlström, Lisen Arnheim, et al. (författare)
  • Prospective study of human papillomavirus and risk of cervical adenocarcinoma.
  • 2010
  • Ingår i: International journal of cancer. Journal international du cancer. - : John Wiley and Sons Inc.. - 1097-0215 .- 0020-7136. ; 127:8, s. 1923-1930
  • Tidskriftsartikel (refereegranskat)abstract
    • Human papillomaviruses (HPV) are established as a major cause of cervical carcinoma. However, causality inference is dependent on prospective evidence showing that exposure predicts risk for future disease. Such evidence is available for squamous cell carcinoma, but not for cervical adenocarcinoma. We followed a population-based cohort of 994,120 women who participated in cytological screening in Sweden for a median of 6.7 years. Baseline smears from women who developed adenocarcinoma during follow-up (118 women with in situ disease and 164 with invasive disease) and their individually matched controls (1,434 smears) were analyzed for HPV using PCR. Conditional logistic regression was used to estimate odds ratios (OR) of future adenocarcinoma with 95% confidence intervals (CI). Being positive for HPV 16 in the first cytologically normal smear was associated with increased risks for both future adenocarcinoma in situ (OR: 11.0, 95% CI: 2.6-46.8) and invasive adenocarcinoma (OR: 16.0, 95% CI: 3.8-66.7), compared to being negative for HPV 16. Similarly, an HPV 18 positive smear was associated with increased risks for adenocarcinoma in situ (OR: 26.0, 95% CI: 3.5-192) and invasive adenocarcinoma (OR: 28.0, 95% CI: 3.8-206), compared to an HPV 18 negative smear. Being positive for HPV 16/18 in 2 subsequent smears was associated with an infinite risk of both in situ and invasive adenocarcinoma. In conclusion, infections with HPV 16 and 18 are detectable up to at least 14 years before diagnosis of cervical adenocarcinoma. Our data provide prospective evidence that the association of HPV 16/18 with cervical adenocarcinoma is strong and causal.
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6.
  • Fall, Tove, et al. (författare)
  • Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors.
  • 2015
  • Ingår i: Diabetes. - : American Diabetes Association Inc.. - 1939-327X .- 0012-1797. ; 64:5, s. 1841-1852
  • Tidskriftsartikel (refereegranskat)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, and 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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7.
  • Fondell, Elinor, et al. (författare)
  • Short natural sleep is associated with higher T cell and lower NK cell activities
  • 2011
  • Ingår i: Brain, behavior, and immunity. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0889-1591 .- 1090-2139. ; 25:7, s. 1367-1375
  • Tidskriftsartikel (refereegranskat)abstract
    • Short sleep duration increases the risk of several diseases, possibly involving compromised immune function. However, most previous studies are based on experimentally induced sleep deprivation, and only a few have studied natural variations in sleep duration. Thus our aim was to study how natural variations in sleep duration affect immune function. In total, 36 healthy men and women, aged 20-54, donated blood; 29 on three consecutive mornings, and seven on one morning. Each morning, participants selfreported sleep duration the night prior to blood draw. General sleep patterns, physical activity and stress were also assessed. A flow-cytometric assay was used to measure natural killer cell activity (NKCA). T cell function (in response to PHA, influenza, and SEA + B), and B cell function (in response to PWM) per volume whole blood. Short sleep duration prior to blood draw (<7 h) was associated with 49% higher PHA-induced T cell function (95% CI 7/109%) and 30% lower NKCA compared with normal prior sleep (7-9 h) (95% CI -46/-8%). In addition, high perceived stress was associated with 39% higher PHA-induced T cell function (95% CI 0/94%). High general physical activity was associated with 47% increased numbers of B cells and 28% increased numbers of T cells, but not with immune function. Our results suggest strong relationships between short sleep duration and T- and NK-cell functions. The stability of the findings as well as the clinical consequences of the link between short sleep and immune function should be explored in future studies. 
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8.
  • Hall, Per, et al. (författare)
  • Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis : a cohort study
  • 2006
  • Ingår i: BMC Medicine. - 1741-7015 .- 1741-7015. ; 4, s. 16-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood. Methods: We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women. Results: HRT use in patients with estrogen receptor ( ER) protein positive tumors (n = 72) was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen. Conclusion: Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells.
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9.
  • Herweijer, Eva, et al. (författare)
  • Association of varying number of doses of quadrivalent human papillomavirus vaccine with incidence of condyloma.
  • 2014
  • Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association. - 1538-3598. ; 311:6, s. 597-603
  • Tidskriftsartikel (refereegranskat)abstract
    • Determining vaccine dose-level protection is essential to minimize program costs and increase mass vaccination program feasibility. Currently, a 3-dose vaccination schedule is recommended for both the quadrivalent and bivalent human papillomavirus (HPV) vaccines. Although the primary goal of HPV vaccination programs is to prevent cervical cancer, condyloma related to HPV types 6 and 11 is also prevented with the quadrivalent vaccine and represents the earliest measurable preventable disease outcome for the HPV vaccine.
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