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- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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- Laitinen, T. V., et al.
(författare)
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Local influence of magnetosheath plasma beta fluctuations on magnetopause reconnection
- 2010
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Ingår i: Annales Geophysicae. - : Copernicus Publications. - 0992-7689 .- 1432-0576. ; 28:5, s. 1053-1063
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Tidskriftsartikel (refereegranskat)abstract
- We present observations from two subsolar Cluster magnetopause crossings under southward interplanetary magnetic field and strong mirror mode fluctuations in the magnetosheath. In both events the reconnection outflow jets show strong variations on the timescale of one minute. We show that at least some of the recorded variations are truly temporal, not spatial. On the same timescale, mirror mode fluctuations appear as strong magnetic fluctuations in the magnetosheath next to the magnetopause. This suggests that mirror modes can cause the variations either through modulation of continuous reconnection or through triggering of bursty reconnection. Using a theoretical scaling law for asymmetric reconnection we show that modulation of reconnection at a single x-line can explain the observations of the first event. The second event cannot be explained by a single modulated x-line: there the evidence points to patchy and bursty reconnection.
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- Pulkkinen, T. I., et al.
(författare)
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Magnetospheric modes and solar wind energy coupling efficiency
- 2010
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 115:3, s. A03207-
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Tidskriftsartikel (refereegranskat)abstract
- Using observations and two different global MHD simulations, we demonstrate that the solar wind speed controls the magnetospheric response such that the higher the speed, the more dynamic and irregular is the magnetospheric response. For similar level of driving solar wind electric field, the magnetospheric modes can be organized in terms of speed: Low speed produces steady convection events, intermediate speeds result in periodic sawtooth oscillations, and high speeds drive large geomagnetic storms. We show that the control parameter of energy transfer and coupling is the electric field along the large-scale X line. We demonstrate using global MHD simulations that for slowly varying interplanetary magnetic field (IMF), the reconnection line is tilted approximately by an angle theta/2, where theta is the IMF clock angle. Then, for clock angles away from northward, the magnetospheric energy entry and response scale with the electric field along the reconnection line (E-PAR), rather than the traditionally used E-Y. If we define the energy coupling efficiency as response/E-PAR, we can show it to be independent of the IMF clock angle and only weakly dependent on the solar wind dynamic pressure. These results demonstrate the ability of the localized reconnection line to control the energy input through the entire magnetopause.
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- Hietala, H., et al.
(författare)
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Supermagnetosonic subsolar magnetosheath jets and their effects : from the solar wind to the ionospheric convection
- 2012
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 30:1, s. 33-48
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Tidskriftsartikel (refereegranskat)abstract
- It has recently been proposed that ripples inherent to the bow shock during radial interplanetary magnetic field (IMF) may produce local high speed flows in the magnetosheath. These jets can have a dynamic pressure much larger than the dynamic pressure of the solar wind. On 17 March 2007, several jets of this type were observed by the Cluster spacecraft. We study in detail these jets and their effects on the magnetopause, the magnetosphere, and the ionospheric convection. We find that (1) the jets could have a scale size of up to a few RE but less than similar to 6 R-E transverse to the XGSE axis; (2) the jets caused significant local magnetopause perturbations due to their high dynamic pressure; (3) during the period when the jets were observed, irregular pulsations at the geostationary orbit and localised flow enhancements in the ionosphere were detected. We suggest that these inner magnetospheric phenomena were caused by the magnetosheath jets.
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