42 research outputs found

    Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease

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    AIMS: To explore whether variability in dietary cholesterol and phytosterol absorption impacts the risk of coronary artery disease (CAD) using as instruments sequence variants in the ABCG5/8 genes, key regulators of intestinal absorption of dietary sterols. METHODS AND RESULTS: We examined the effects of ABCG5/8 variants on non-high-density lipoprotein (non-HDL) cholesterol (N up to 610 532) and phytosterol levels (N = 3039) and the risk of CAD in Iceland, Denmark, and the UK Biobank (105 490 cases and 844 025 controls). We used genetic scores for non-HDL cholesterol to determine whether ABCG5/8 variants confer greater risk of CAD than predicted by their effect on non-HDL cholesterol. We identified nine rare ABCG5/8 coding variants with substantial impact on non-HDL cholesterol. Carriers have elevated phytosterol levels and are at increased risk of CAD. Consistent with impact on ABCG5/8 transporter function in hepatocytes, eight rare ABCG5/8 variants associate with gallstones. A genetic score of ABCG5/8 variants predicting 1 mmol/L increase in non-HDL cholesterol associates with two-fold increase in CAD risk [odds ratio (OR) = 2.01, 95% confidence interval (CI) 1.75-2.31, P = 9.8 × 10-23] compared with a 54% increase in CAD risk (OR = 1.54, 95% CI 1.49-1.59, P = 1.1 × 10-154) associated with a score of other non-HDL cholesterol variants predicting the same increase in non-HDL cholesterol (P for difference in effects = 2.4 × 10-4). CONCLUSIONS: Genetic variation in cholesterol absorption affects levels of circulating non-HDL cholesterol and risk of CAD. Our results indicate that both dietary cholesterol and phytosterols contribute directly to atherogenesis

    Genome-wide association metaanalysis of human longevity identifies a novel locus conferring survival beyond 90 years of age. Hum Mol Genet.

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    Flux limits on ultra high energy neutrinos with AMANDA-B10

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    Abstract Data taken during 1997 with the AMANDA-B10 detector are searched for a diffuse flux of neutrinos of all flavors with energies above 10 16 eV. At these energies the Earth is opaque to neutrinos, and thus neutrino induced events are concentrated at the horizon. The background are large muon bundles from down-going atmospheric air shower events. No excess events above the background expectation are observed and a neutrino flux following E À2 , with an equal mix of all flavors, is limited to E 2 U(10 15 eV < E < 3 · 10 18 eV) 6 0.99 · 10 À6 GeV cm À2 s À1 sr À1 at 90% confidence level. This is the most restrictive experimental bound placed by any neutrino detector at these energies. Bounds to specific extraterrestrial neutrino flux predictions are also presented. Ó 2004 Elsevier B.V. All rights reserved. PACS: 95.55.Vj; 95.85.Ry; 96.40.T
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