| 1. |
- Dubois, Kévin, 1995-, et al.
(författare)
-
Technical note : Extending sea level time series for the analysis of extremes with statistical methods and neighbouring station data
- 2024
-
Ingår i: Ocean Science. - : Copernicus Publications. - 1812-0784 .- 1812-0792. ; 20:1, s. 21-30
-
Tidskriftsartikel (refereegranskat)abstract
- Extreme sea levels may cause damage and the disruption of activities in coastal areas. Thus, predicting extreme sea levels is essential for coastal management. Statistical inference of robust return level estimates critically depends on the length and quality of the observed time series. Here, we compare two different methods for extending a very short (∼ 10-year) time series of tide gauge measurements using a longer time series from a neighbouring tide gauge: linear regression and random forest machine learning. Both methods are applied to stations located in the Kattegat Basin between Denmark and Sweden. Reasonable results are obtained using both techniques, with the machine learning method providing a better reconstruction of the observed extremes. By generating a set of stochastic time series reflecting uncertainty estimates from the machine learning model and subsequently estimating the corresponding return levels using extreme value theory, the spread in the return levels is found to agree with results derived by more physically based methods.
|
|
| 2. |
|
|
| 3. |
- Thun, Gian Andri, et al.
(författare)
-
Causal and Synthetic Associations of Variants in the SERPINA Gene Cluster with Alpha1-antitrypsin Serum Levels
- 2013
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:8, s. e1003585-
-
Tidskriftsartikel (refereegranskat)abstract
- Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT) in the blood. Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation these polymorphisms also increase the risk for early onset chronic obstructive pulmonary disease (COPD). The role of more common SERPINA1 single nucleotide polymorphisms (SNPs) in respiratory health remains poorly understood. We present here an agnostic investigation of genetic determinants of circulating AAT levels in a general population sample by performing a genome-wide association study (GWAS) in 1392 individuals of the SAPALDIA cohort. Five common SNPs defined by showing minor allele frequencies (MAFs) >5% reached genome-wide significance all located in the SERPINA gene cluster at 14q32.13. The top-ranking genotyped SNP rs4905179 was associated with an estimated effect of beta = 20.068 g/L per minor allele (P = 1.20*10(-12)). But denser SERPINA1 locus genotyping in 5569 participants with subsequent stepwise conditional analysis as well as exon-sequencing in a subsample (N = 410) suggested that AAT serum level is causally determined at this locus by rare (MAF<1%) and low-frequent (MAF 1-5%) variants only in particular by the well-documented protein inhibitor S and Z (PI S PI Z) variants. Replication of the association of rs4905179 with AAT serum levels in the Copenhagen City Heart Study (N = 8273) was successful (P<0.0001) as was the replication of its synthetic nature (the effect disappeared after adjusting for PI S and Z P = 0.57). Extending the analysis to lung function revealed a more complex situation. Only in individuals with severely compromised pulmonary health (N = 397) associations of common SNPs at this locus with lung function were driven by rarer PI S or Z variants. Overall our meta-analysis of lung function in ever-smokers does not support a functional role of common SNPs in the SERPINA gene cluster in the general population.
|
|
