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- Schmidt, Amand F., et al.
(författare)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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| 2. |
- Baumeister, Sebastian E., et al.
(författare)
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Association between physical activity and risk of hepatobiliary cancers : A multinational cohort study
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 70:5, s. 885-892
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: To date, evidence on the association between physical activity and risk of hepatobiliary cancers has been inconclusive. We examined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).Methods: We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cancers (NGBCs) among 467,336 EPIC participants (median follow-up 14.9 years). We estimated cause-specific hazard ratios (HRs) for total physical activity and vigorous physical activity and performed mediation analysis and secondary analyses to assess robustness to confounding (e.g. due to hepatitis virus infection).Results: In the EPIC cohort, the multivariable-adjusted HR of HCC was 0.55 (95% CI 0.38–0.80) comparing active and inactive individuals. Regarding vigorous physical activity, for those reporting >2 hours/week compared to those with no vigorous activity, the HR for HCC was 0.50 (95% CI 0.33–0.76). Estimates were similar in sensitivity analyses for confounding. Total and vigorous physical activity were unrelated to IHBC and NGBC. In mediation analysis, waist circumference explained about 40% and body mass index 30% of the overall association of total physical activity and HCC.Conclusions: These findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity.Lay summary: In a pan-European study of 467,336 men and women, we found that physical activity is associated with a reduced risk of developing liver cancers over the next decade. This risk was independent of other liver cancer risk factors, and did not vary by age, gender, smoking status, body weight, and alcohol consumption.
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| 3. |
- Pabst, Alexander, et al.
(författare)
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Decomposing social inequalities in alcohol consumption in Germany 1995-2015 : an age-period-cohort analysis
- 2019
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Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 114:8, s. 1359-1368
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims Previous research indicates that compared with individuals with lower socio-economic status (SES), individuals in higher SES groups are more often drinkers but those who drink report drinking smaller amounts more frequently. We aimed to decompose trends in self-reported alcohol consumption in Germany into age, period and birth cohort effects and examine whether these effects varied by SES. Design Age-period-cohort (APC) analysis using data from eight waves of the cross-sectional German Epidemiological Survey of Substance Abuse (ESA) collected between 1995 and 2015. Setting Germany. Participants The analytical sample included n=65821 individuals aged 18-64years reporting alcohol use within the last 30days. Measurements Alcohol measures included drinking prevalence, alcohol volume and prevalence of episodic heavy drinking (EHD). Educational attainment was used as an indicator of SES. A series of generalized linear and logistic regression models, including both main and interaction effects of age, period and cohort with SES, were estimated. Findings Regression models revealed significant interactions between APC effects and SES on two alcohol consumption measures. Higher SES was consistently associated with drinking prevalence across age (P<0.001), period (P=0.016) and cohort (P=0.016), and with volume of drinking in younger cohorts (P=0.002) and 50+-year-olds (P=0.001). Model results were inconclusive as to whether or not APC effects on EHD prevalence differed by SES. Conclusions In Germany, there are positive associations between socio-economic status and alcohol consumption during the life-course, over time and among birth cohorts. Three groups appear vulnerable to risky drinking: high socio-economic status young birth cohorts who drink high average quantities, low socio-economic status young birth cohorts who show a risky drinking pattern and high socio-economic status adults in their 50s and older who increase their drinking volume beyond that age.
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