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- Asselbergs, Folkert W., et al.
(författare)
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Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci
- 2012
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 91:5, s. 823-838
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.
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| 2. |
- Nik, Vahid, 1979, et al.
(författare)
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Climate Change and Wind-Driven Rain – a Preliminary Study about Climate Uncertainties
- 2013
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Ingår i: Proceedings of FutureBuild 2013; University of Bath, UK.
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Konferensbidrag (refereegranskat)abstract
- Under changing climate conditions, acceptable functionality of buildings and their adaptation to climate are required. More rain and extreme conditions in future make buildings and the built environment more vulnerable. There are currently several scenarios regarding possible future climatic conditions. Results from the impact analysis of climate change can be significantly affected by the selected climate scenario. Therefore it is recommended to do not rely on few climate scenarios while performing the impact analysis. This paper suggests a simple method to analyse the importance of climate uncertainties in the impact assessment of climate change on wind-driven rain (WDR). The method is based on the calculation of Stokes number; a dimensionless number which correlates strongly with the catch ratio of the wind-driven rain. Preliminary results have been obtained by studying the distribution of Stokes number during 1961-2100 for several climate scenarios. Distributions demonstrate the probable differences in WDR calculations, induced by the climate uncertainties. Three uncertainty factors are considered in this work; global climate models, initial conditions and spatial resolutions of the climate scenarios. Based on the results all the three factors can induce changes in WDR calculations. However the magnitudes of changes are not the same among the uncertainty factors. Using the Stokes number helps to evaluate the importance of climate uncertainties before the WDR simulations.
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