1. |
- Marouli, Eirini, et al.
(författare)
-
Rare and low-frequency coding variants alter human adult height
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
|
|
2. |
- Piroddi, Chiara, et al.
(författare)
-
Effects of Nutrient Management Scenarios on Marine Food Webs : A Pan-European Assessment in Support of the Marine Strategy Framework Directive
- 2021
-
Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 8
-
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.
|
|