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- 2019
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Tidskriftsartikel (refereegranskat)
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- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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- Le Contel, O., et al.
(författare)
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The Search-Coil Magnetometer for MMS
- 2016
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Ingår i: Space Science Reviews. - : Springer Netherlands. - 0038-6308 .- 1572-9672. ; 199:1-4, s. 257-282
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Forskningsöversikt (refereegranskat)abstract
- The tri-axial search-coil magnetometer (SCM) belongs to the FIELDS instrumentation suite on the Magnetospheric Multiscale (MMS) mission (Torbert et al. in Space Sci. Rev. (2014), this issue). It provides the three magnetic components of the waves from 1 Hz to 6 kHz in particular in the key regions of the Earth's magnetosphere namely the subsolar region and the magnetotail. Magnetospheric plasmas being collisionless, such a measurement is crucial as the electromagnetic waves are thought to provide a way to ensure the conversion from magnetic to thermal and kinetic energies allowing local or global reconfigurations of the Earth's magnetic field. The analog waveforms provided by the SCM are digitized and processed inside the digital signal processor (DSP), within the Central Electronics Box (CEB), together with the electric field data provided by the spin-plane double probe (SDP) and the axial double probe (ADP). On-board calibration signal provided by DSP allows the verification of the SCM transfer function once per orbit. Magnetic waveforms and on-board spectra computed by DSP are available at different time resolution depending on the selected mode. The SCM design is described in details as well as the different steps of the ground and in-flight calibrations.
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