Aims/hypothesisFTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.MethodsAll studies published on the association between FTO-rs9939609 (or proxy [r2 > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.ResultsThe FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10−19), overweight by 1.13-fold/allele (p = 1.0 × 10−11) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10−8). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10−5). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10−17), WHR by 0.003/allele (p = 1.2 × 10−6), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations.Conclusions/interpretationFTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

We use smoothed particle hydrodynamics simulations with an approximate radiative cooling prescription to model the evolution of a massive (∼100 au) very young protoplanetary disc. We also model dust growth and gas‐grain dynamics with a second fluid approach. It is found that the disc fragments into a large number of ∼10MJ clumps that cool and contract slowly. Some of the clumps evolve on to eccentric orbits, delivering them into the inner tens of au, where they are disrupted by tidal forces from the star. Dust grows and sediments inside the clumps, displaying a very strong segregation, with the largest particles forming dense cores in the centres. The density of the dust cores in some cases exceeds that of the gas and is limited only by the numerical constraints, indicating that these cores should collapse into rocky planetary cores. One particular giant planet embryo migrates inwards close enough to be disrupted at about 10 au, leaving a self‐bound solid core of about 7.5  M⊕ mass on a low‐eccentricity orbit at a radius of ∼8 au. These simulations support the recent suggestions that terrestrial and giant planets may be the remnants of tidally disrupted giant planet embryos.

Godunov-type particle hydrodynamics (GPH) is described. GPH inherits many good features from smoothed particle hydrodynamics (SPH), but it uses a Riemann solver to obtain the hydrodynamic acceleration and the rate of change of the internal energy of each particle. The grid-free nature of GPH converts a multidimensional problem into a locally one-dimensional problem, so that one only has to solve a one-dimensional Riemann problem, even in a globally three-dimensional situation. By virtue of the Riemann solver, it is unnecessary to introduce artificial viscosity in GPH. We have derived four different versions of GPH, and have performed a von Neumann stability analysis to understand the nature of GPH. GPH is stable for all wavelengths, while SPH is unstable for certain wavelengths. We have also performed eight tests in order to evaluate the performance of GPH. The results show that GPH can describe shock waves without artificial viscosity and prevents particle penetration. Furthermore, GPH shows better performance than SPH in a test involving velocity shear. GPH is easily implemented from SPH by simple replacement of the artificial viscosity with a Riemann solver, and appears to have some useful advantages over standard SPH.

It has been newly reported in recent studies that single-nucleotide polymorphisms (SNPs) in the first intron of the FTO gene have been associated with BMI in whites. To determine whether the gene is associated with BMI in Asians also, we performed a replication study of the association of the gene with BMI in a Korean population. Two SNPs in the FTO gene (rs1421085 and rs17817449) were genotyped using the TaqMan method in a Korean population (n = 1,733). The two SNPs were then used for an association study with BMI through statistical analyses. The rs1421085 C allele (P = 0.0015, effect size = 0.0056) and rs17817449 G allele (P = 0.0019, effect size = 0.0053) were found to be significantly associated with increased BMI. Our results suggest that FTO may be one of the worldwide obesity-risk genes.Obesity (2008) 16, 2187-2189. doi:10.1038/oby.2008.314 Obesity is one of the most common disorders in clinical practice and is closely related to a number of pathological disorders such as noninsulin-dependent diabetes, hypertension, cancer, gallbladder disease, and atherosclerosis. A large number of genetic association studies suggest that polymorphic variants in genes are associated with BMI (1).Recently, three independent studies have found that common variants in intron 1 of the FTO gene (fat mass and obesity associated; #MIM:610966) were found to be associated with BMI (2-4), and those findings have been replicated in several white populations (3,5,6). However, among other ethnic populations (Asians and Africans), the genetic effects of polymorphisms in intron 1 of FTO have been controversial. The rs9930506 was not associated with obesity-related phenotypes including BMI, weight, and hip circumference in 1,101 African Americans (4). In addition, among oceanic populations (Melanesians, Micronesians, and Polynesians), rs9939609 was not associated with BMI (7). In a Japanese population (864 type 2 diabetes patients and 864 controls), rs8050136 and rs9939690 were not found to be associated with BMI either, although one variant, rs8050136, was associated with the risk of type 2 diabetes (8).A number of highly linked single-nucleotide polymorphisms (SNPs) have been reported to be associated with BMI in previous studies. In this study, in an effort to replicate the association with BMI among Asians, we examined genetic effects in a Korean cohort (n = 1,733) with two SNPs (rs1421085 and rs17817449) that had been reported in white populations (3). To compare the genetic effects directly, we selected the two The genotype distributions of the two SNPs (rs1421085 and rs17817449) in high-BMI individuals (>25 (kg/m 2 )) were in Hardy-Weinberg equilibrium (P = 0.84 and 0.97, respectively). However, genotype distributions among low-BMI individuals (≤25 (kg/m 2 )) were significantly deviated from HardyWeinberg equilibrium (P = 0.011 for rs1421085 and P = 0.011 for rs17817449). Those deviations of FTO variants might be indirect evidence for association of those variants with BMI. The minor allele frequencies of rs1421085 and rs1781...

We investigate numerically and semi-analytically the collapse of low-mass, rotating prestellar cores. Initially, the cores are in approximate equilibrium with low rotation (the initial ratio of thermal to gravitational energy is α 0 0.5, and the initial ratio of rotational to gravitational energy is β 0 = 0.02-0.05). They are then subjected to a steady increase in external pressure. Fragmentation is promoted -in the sense that more protostars are formed -both by more rapid compression, and by higher rotation (larger β 0 ).In general, the large-scale collapse is non-homologous, and follows the pattern described by Hennebelle et al. (Paper I) for non-rotating clouds, namely a compression wave is driven into the cloud, thereby increasing the density and the inflow velocity. The effects of rotation become important at the centre, where the material with low angular momentum forms a central primary protostar (CPP), whilst the material with higher angular momentum forms an accretion disc around the CPP. More rapid compression drives a stronger compression wave and delivers material more rapidly into the outer parts of the disc. Consequently, (i) there is more mass in the outer parts of the disc; (ii) the outer parts of the disc are denser (because the density of the material running into the accretion shock at the edge of the disc is higher); and (iii) there is less time for the gravitational torques associated with symmetry breaking to redistribute angular momentum and thereby facilitate accretion on to the CPP. The combination of a massive, dense outer disc and a relatively low-mass CPP renders the disc unstable against fragmentation, and leads to the formation of one or more secondary protostars. At their inception, these secondary protostars are typically four or five times less massive than the CPP.For very rapid compression there is no CPP and the disc becomes more like a ring, which then fragments into two or three protostars of comparable mass.For more rapid rotation (larger β 0 ), the outer disc is even more massive in comparison to the CPP, even more extended, and therefore even more prone to fragment.

BackgroundFace morphology is strongly determined by genetic factors. However, only a small number of genes related to face morphology have been identified to date. Here, we performed a two-stage genome-wide association study (GWAS) of 85 face morphological traits in 7569 Koreans (5643 in the discovery set and 1926 in the replication set).ResultsIn this study, we analyzed 85 facial traits, including facial angles. After discovery GWAS, 128 single nucleotide polymorphisms (SNPs) showing an association of P < 5 × 10− 6 were selected to determine the replication of the associations, and meta-analysis of discovery GWAS and the replication analysis resulted in five genome-wide significant loci. The OSR1-WDR35 [rs7567283, G allele, beta (se) = −0.536 (0.096), P = 2.75 × 10− 8] locus was associated with the facial frontal contour; the HOXD1-MTX2 [rs970797, A allele, beta (se) = 0.015 (0.003), P = 3.97 × 10− 9] and WDR27 [rs3736712, C allele, beta (se) = 0.293 (0.048), P = 8.44 × 10− 10] loci were associated with eye shape; and the SOX9 [rs2193054, C allele, beta (se) (ln-transformed) = −0.007 (0.001), P = 6.17 × 10− 17] and DHX35 [rs2206437, A allele, beta (se) = −0.283 (0.047), P = 1.61 × 10− 9] loci were associated with nose shape. WDR35 and SOX9 were related to known craniofacial malformations, i.e., cranioectodermal dysplasia 2 and campomelic dysplasia, respectively. In addition, we found three independent association signals in the SOX9 locus, and six known loci for nose size and shape were replicated in this study population. Interestingly, four SNPs within these five face morphology-related loci showed discrepancies in allele frequencies among ethnic groups.ConclusionsWe identified five novel face morphology loci that were associated with facial frontal contour, nose shape, and eye shape. Our findings provide useful genetic information for the determination of face morphology.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4865-9) contains supplementary material, which is available to authorized users.

Numerical simulations for the non‐linear development of Kelvin–Helmholtz instability in two different density layers have been performed with the particle‐based method (Godunov SPH) developed by Inutsuka. The Godunov SPH can describe the Kelvin–Helmholtz instability even with a high‐density contrast, while the standard SPH shows the absence of the instability across a density gradient. The interaction of a dense blob with a hot ambient medium has been performed also. The Godunov SPH describes the formation and evolution of the fingers due to the combinations of Rayleigh–Taylor, Richtmyer–Meshkov and Kelvin–Helmholtz instabilities. The blob test result coincides well with the results of the grid‐based codes. An inaccurate handling of a density gradient in the standard SPH has been pointed out as the direct reason of the absence of the instabilities. An unphysical force happens at the density gradient even in a pressure equilibrium, and repulses particles from the initial density discontinuity. Therefore, the initial perturbation damps, and a gap form at the discontinuity. The unphysical force has been studied in terms of the consistency of a numerical scheme. Contrary to the standard SPH, the momentum equation of the Godunov SPH does not use the particle approximation, and has been derived from the kernel convolution or a new Lagrangian function. The new Lagrangian function used in the Godunov SPH is more analogous to the real Lagrangian function for continuum. The momentum equation of the Godunov SPH has much better linear consistency, so the unphysical force is greatly reduced compared to the standard SPH in a high density contrast.

Core Accretion, the most widely accepted scenario for planet formation, postulates existence of km-sized solid bodies, called planetesimals, arranged in a razor-thin disc in the earliest phases of planet formation. In the Tidal Downsizing hypothesis, an alternative scenario for formation of planets, grain growth, sedimentation and formation of planetary cores occur inside dense and massive gas clumps formed in the outer cold disc by gravitational instability. As a clump migrates inward, tidal forces of the star remove all or most of the gas from the clump, downsizing it to a planetary mass body. Here we argue that such a clump may form not only the planetary core but also numerous smaller bodies. As an example, we consider the simplest case of bodies on circular orbits around the planetary core in the centre of the gas clump. Bodies smaller than 1 km suffer a strong enough aerodynamic drag, spiral in and accrete onto the solid core rapidly; bodies in the planetesimal size range lose their centrifugal support very slowly. We find that planetesimals orbiting the protoplanetary core closely remain gravitationally bound to it; these may be relevant to formation of satellites of giant planets. Planetesimals on more distant orbits within the host clump are unbound from the protoplanet and are set on mildly eccentric heliocentric orbits, generically forming wide rings. These may correspond to debris discs around main sequence stars and the Kuiper belt in the Solar System. For the latter in particular, our hypothesis naturally explains the observed sharp outer edge and the "mass deficit" of the Kuiper belt.Comment: Submitted to MNRA