| 1. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 2. |
- Smith, Caren E., et al.
(författare)
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Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent
- 2018
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Ingår i: Molecular Nutrition & Food Research. - : Wiley. - 1613-4125. ; 62:3
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Tidskriftsartikel (refereegranskat)abstract
- Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption. Methods and results: A genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction <10−7), and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3’ of LINC00333) was replicated (p-interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p-interaction = 7.36 × 10−8) such that each serving of low-fat dairy was associated with 0.225 kg m−2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure. Conclusion: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight.
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| 3. |
- Piroddi, Chiara, et al.
(författare)
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Effects of Nutrient Management Scenarios on Marine Food Webs : A Pan-European Assessment in Support of the Marine Strategy Framework Directive
- 2021
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Eutrophication is one of the most important anthropogenic pressures impacting coastal seas. In Europe, several legislations and management measures have been implemented to halt nutrient overloading in marine ecosystems. This study evaluates the impact of freshwater nutrient control measures on higher trophic levels (HTL) in European marine ecosystems following descriptors and criteria as defined by the Marine Strategy Framework Directive (MSFD). We used a novel pan-European marine modeling ensemble of fourteen HTL models, covering almost all the EU seas, under two nutrient management scenarios. Results from our projections suggest that the proposed nutrient reduction measures may not have a significant impact on the structure and function of European marine ecosystems. Among the assessed criteria, the spawning stock biomass of commercially important fish stocks and the biomass of small pelagic fishes would be the most impacted, albeit with values lower than 2.5%. For the other criteria/indicators, such as species diversity and trophic level indicators, the impact was lower. The Black Sea and the North-East Atlantic were the most negatively impacted regions, while the Baltic Sea was the only region showing signs of improvement. Coastal and shelf areas were more sensitive to environmental changes than large regional and sub-regional ecosystems that also include open seas. This is the first pan-European multi-model comparison study used to assess the impacts of land-based measures on marine and coastal European ecosystems through a set of selected ecological indicators. Since anthropogenic pressures are expanding apace in the marine environment and policy makers need to use rapid and effective policy measures for fast-changing environments, this modeling framework is an essential asset in supporting and guiding EU policy needs and decisions.
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