| 1. |
- McCarthy, Shane, et al.
(författare)
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A reference panel of 64,976 haplotypes for genotype imputation
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1279-1283
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Tidskriftsartikel (refereegranskat)abstract
- We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.
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| 2. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 3. |
- Petersmann, Astrid, et al.
(författare)
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Impact of physical activity of individuals and creatine kinase on 99th percentiles of troponin I assays
- 2016
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 462, s. 187-192
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Tidskriftsartikel (refereegranskat)abstract
- Determination of cardiac troponin I (cTnI) is one central means for diagnosis of myocardial infarction. Assay performance of three troponin I assays was compared previously in a large reference population detecting sex-differences in the 99th percentile only for the Dimension Vista cTnI assay. The present study examined the underlying effects. Values for cTnI were reused. Creatine kinase (CK) activity was determined in 2358 samples from blood donors. Information on physical activity was evaluated from health questionnaires. Using quantile regression data were analysed to investigate the impact of sex, physical activity, and CK on the 99th percentile of the cTnI assay. We report significant sex-differences for the 99th percentile of cTnI. Physical activity was significantly associated with cTnI values. Strong association of CK activity with cTnI values was detected only in men. Adjustment for CK in quantile regression abolished sex -differences in the 99th percentile. Two other contemporary sensitive cTnI assays were not relevantly affected by physical activity or CK. Sex -differences in the 99th percentile for the Dimension Vista cTnI assay arise from a positive association between cTnI and physical activity and were abrogated when data were adjusted for CK activity. These findings should be taken into account when using this assay.
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