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- Kathiresan, Sekar, et al.
(author)
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Common variants at 30 loci contribute to polygenic dyslipidemia
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 56-65
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Journal article (peer-reviewed)abstract
- Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.
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| 2. |
- Sayer, Carl D., et al.
(author)
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The application of palaeolimnology to evidence-based lake management and conservation: examples from UK lakes
- 2012
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In: Aquatic conservation. - : John Wiley & Sons, Ltd. - 1052-7613 .- 1099-0755. ; 22:2, s. 165-180
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Journal article (peer-reviewed)abstract
- * To help meet the requirements of water legislation, palaeolimnology has been widely used to establish ‘reference conditions’ and restoration targets for lakes. However, its potential for assessing the necessity and appropriateness of different lake management activities has been less publicized. * With reference to selected case studies covering consultancy projects commissioned by UK conservation agencies, this study highlights the important applied role of palaeolimnology. Using varying combinations of diatom, plant macrofossil and cladoceran analysis, the degree, timing and in many cases the likely drivers of ecological change were inferred for several lake sites. * From this basis advice was given on a range of lake management issues, including the need for sediment removal to combat eutrophication and/or the necessity of other nutrient reduction measures (Case study 1), the depth of sediment to be removed to maximize restoration potential through exposure of dormant banks of characean oospores (Case study 2), the requirement for fish management (Case study 3), and advice regarding fish farm expansion and licensing (Case study 4). Where possible management responses to the recommendations are outlined including any major outcomes. * All case studies illustrate the advantages, for lake management and conservation decision-making, of placing current lake ecological conditions in the context of long-term change. Copyright © 2012 John Wiley & Sons, Ltd.
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| 3. |
- Voight, Benjamin F, et al.
(author)
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Plasma HDL cholesterol and risk of myocardial infarction : a mendelian randomisation study
- 2012
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9841, s. 572-580
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Journal article (peer-reviewed)abstract
- BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.FINDINGS: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69-2·69, p=2×10(-10)).INTERPRETATION: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.
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