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Genetic predictions of height differ among human populations and these differences have been interpreted as evidence of polygenic adaptation. These differences were first detected using SNPs genome-wide significantly associated with height, and shown to grow stronger when large numbers of sub-significant SNPs were included, leading to excitement about the prospect of analyzing large fractions of the genome to detect polygenic adaptation for multiple traits. Previous studies of height have been based on SNP effect size measurements in the GIANT Consortium meta-analysis. Here we repeat the analyses in the UK Biobank, a much more homogeneously designed study. We show that polygenic adaptation signals based on large numbers of SNPs below genome-wide significance are extremely sensitive to biases due to uncorrected population stratification. More generally, our results imply that typical constructions of polygenic scores are sensitive to population stratification and that population-level differences should be interpreted with caution. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter ).

Joel Hirschhorn and colleagues examine height-associated SNPs in northern- and southern-European populations. They report evidence of widespread weak selection on standing variation for height in humans. Strong signatures of positive selection at newly arising genetic variants are well documented in humans 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , but this form of selection may not be widespread in recent human evolution 9 . Because many human traits are highly polygenic and partly determined by common, ancient genetic variation, an alternative model for rapid genetic adaptation has been proposed: weak selection acting on many pre-existing (standing) genetic variants, or polygenic adaptation 10 , 11 , 12 . By studying height, a classic polygenic trait, we demonstrate the first human signature of widespread selection on standing variation. We show that frequencies of alleles associated with increased height, both at known loci and genome wide, are systematically elevated in Northern Europeans compared with Southern Europeans ( P < 4.3 × 10 −4 ). This pattern mirrors intra-European height differences and is not confounded by ancestry or other ascertainment biases. The systematic frequency differences are consistent with the presence of widespread weak selection (selection coefficients ∼10 −3 –10 −5 per allele) rather than genetic drift alone ( P < 10 −15 ).

Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. PA has at least a 50% higher incidence in populations of European ancestry compared to other ancestral groups, which may be due in part to genetic differences. We first compared the global proportions of European, African, and Amerindian ancestries in 301 PA cases and 1185 controls of self-identified Latino ethnicity from the California Biobank. We then conducted admixture mapping analysis to assess PA risk with local ancestry. We found PA cases had a significantly higher proportion of global European ancestry than controls (case median = 0.55, control median = 0.51, P value = 3.5x10-3). Admixture mapping identified 13 SNPs in the 6q14.3 region (SNX14) contributing to risk, as well as three other peaks approaching significance on chromosomes 7, 10 and 13. Downstream fine mapping in these regions revealed several SNPs potentially contributing to childhood PA risk. There is a significant difference in genomic ancestry associated with Latino PA risk and several genomic loci potentially mediating this risk.

As are most non-European populations, the Han Chinese are relatively understudied in population and medical genetics studies. From low-coverage whole-genome sequencing of 11,670 Han Chinese women we present a catalog of 25,057,223 variants, including 548,401 novel variants that are seen at least 10 times in our data set. Individuals from this data set came from 24 out of 33 administrative divisions across China (including 19 provinces, 4 municipalities, and 1 autonomous region), thus allowing us to study population structure, genetic ancestry, and local adaptation in Han Chinese. We identified previously unrecognized population structure along the East–West axis of China, demonstrated a general pattern of isolation-by-distance among Han Chinese, and reported unique regional signals of admixture, such as European influences among the Northwestern provinces of China. Furthermore, we identified a number of highly differentiated, putatively adaptive, loci (e.g., MTHFR, ADH7, and FADS, among others) that may be driven by immune response, climate, and diet in the Han Chinese. Finally, we have made available allele frequency estimates stratified by administrative divisions across China in the Geography of Genetic Variant browser for the broader community. By leveraging the largest currently available genetic data set for Han Chinese, we have gained insights into the history and population structure of the world’s largest ethnic group.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy. Given racial/ethnic differences in incidence and outcomes, B-ALL genome-wide association studies among children of African ancestry are needed. Leveraging multi-institutional datasets with 840 African American children with B-ALL and 3360 controls, nine loci achieved genome-wide significance ( P  < 5 × 10 −8 ) after meta-analysis. Two loci were established trans-ancestral susceptibility regions ( IKZF1 , ARID5B ), while the remaining novel loci were specific to African populations. Five-year overall survival among children carrying novel risk alleles was significantly worse (83% versus 96% in non-carriers, P  = 4.8 × 10 −3 ). Novel risk variants were also associated with subtype-specific disease ( P  < 0.05), including higher susceptibility for a subtype overrepresented in African American children ( TCF3-PBX1 ) and lower susceptibility for a subtype with excellent prognosis ( ETV6-RUNX1 ). Functional experiments revealed novel B-ALL risk variants had allele-specific differences in transcriptional activity ( P  < 0.05) in B-cell and leukemia cell lines. These findings shed insights into ancestry-related differences in leukemogenesis and prognosis. Disparities in risk and outcomes of pediatric acute lymphoblastic leukemia (ALL) are apparent between different ancestries. Here the authors identify genetic variants with African ancestry-specific risks for developing pediatric B-cell ALL that are also linked to greater 5-year mortality risk.

The island of Sardinia has been of particular interest to geneticists for decades. The current model for Sardinia’s genetic history describes the island as harboring a founder population that was established largely from the Neolithic peoples of southern Europe and remained isolated from later Bronze Age expansions on the mainland. To evaluate this model, we generate genome-wide ancient DNA data for 70 individuals from 21 Sardinian archaeological sites spanning the Middle Neolithic through the Medieval period. The earliest individuals show a strong affinity to western Mediterranean Neolithic populations, followed by an extended period of genetic continuity on the island through the Nuragic period (second millennium BCE). Beginning with individuals from Phoenician/Punic sites (first millennium BCE), we observe spatially-varying signals of admixture with sources principally from the eastern and northern Mediterranean. Overall, our analysis sheds light on the genetic history of Sardinia, revealing how relationships to mainland populations shifted over time. Ancient DNA analysis of early European farmers has found a high level of genetic affinity with present-day Sardinians. Here, the authors generate genome-wide capture data for 70 individuals from Sardinia spanning the Middle Neolithic to Medieval period to reveal relationships with mainland European populations shifting over time.

The multi-sensor fusion scheme has become more and more popular these days with its great potential to estimate reliable navigation information for the modern development in automated driving system (ADS) and mobile mapping systems (MMS). Since these systems are combined with numerous navigation sensors, thus their geometric relationship should be precisely known. This study focuses on practical aspects when calibrating LiDAR-IMU mounting parameters (lever-arms and bore-sight angles) in land-based MMS. This calibration model is based on expressing the mounting parameters within the direct georeferencing equation for each epoch time and conditioning a set of INS/GNSS and LiDAR navigation solutions to lie on it. There is no need for a required information about the planar features in the calibration field as part of the unknowns. Such conditions are only benefitable in the residential area where the presence of sufficient planes in form of building is abundant. We present an approach for recovery the mounting parameters by conditioning the high-definition (HD) point cloud map-based LiDAR information and INS/GNSS navigation solutions through the least-squares solutions. The presented results and discussion mainly focus on practical examples with data from land-based MMS. Preliminary results indicate that correct calibration parameters are not only capable to improve the performance of point cloud georeferencing but also dramatically provide reliable performance evaluation of navigation estimation. Moreover, these findings show that the studied method is not only applicable in the featureless environment but also in its practicality to the self-driving applications.

In recent years, a lot of researchers have been trying the development of efficient ways to create HD maps with centimeter-level precision. Mobile mapping system (MMS) produce 3D HD point cloud map of the surrounding by integrating navigation (i.e., direct georeferencing or DG process) and high-resolution imaging sensor data. Unfortunately, in partially environments, the provided accuracy of the GNSS system degrades dramatically. In order to constraint the drift and correct the georeferenced point cloud map, ground control points (GCPs) are placed along the road. Moreover, there are approaches which use laser-based point cloud registration techniques to construct the point cloud map. However, all promising mapping techniques which currently use the laser as the core sensor for mapping the high-definition point cloud map may not be promised to construct the point cloud map in partially or unfriendly environments. As a literature review and result, a suitable approach for creating the promising point cloud map is to combine the INS/GNSS navigation solution, LiDAR matching techniques, and GCPs. Thus, this study introduces the HD point cloud map generation method that can potentially help researchers create personalized and globalized HD point cloud maps and develop new HD point cloud map generation methodologies.

Exome-sequencing studies have generally been underpowered to identify deleterious alleles with a large effect on complex traits as such alleles are mostly rare. Because the population of northern and eastern Finland has expanded considerably and in isolation following a series of bottlenecks, individuals of these populations have numerous deleterious alleles at a relatively high frequency. Here, using exome sequencing of nearly 20,000 individuals from these regions, we investigate the role of rare coding variants in clinically relevant quantitative cardiometabolic traits. Exome-wide association studies for 64 quantitative traits identified 26 newly associated deleterious alleles. Of these 26 alleles, 19 are either unique to or more than 20 times more frequent in Finnish individuals than in other Europeans and show geographical clustering comparable to Mendelian disease mutations that are characteristic of the Finnish population. We estimate that sequencing studies of populations without this unique history would require hundreds of thousands to millions of participants to achieve comparable association power. Exome-wide sequencing studies of populations in Finland identified 26 deleterious alleles associated with 64 quantitative traits that are clinically relevant to cardiovascular and metabolic diseases.

Over recent years, the utilization of commercially available integrated navigation systems for the development of navigation algorithms has become increasingly commonplace. Nevertheless, the wide range of sensor quality on the market complicates system customization and restricts the evolution of navigation algorithms. This study aims to address these issues by creating an affordable, tactical-grade, real-time integrated navigation system, EGI-500 (Embedded GNSS and INS), encompassing both hardware and software components. EGI-500 incorporates a tactical-grade IMU500 and a Septentrio Mosaic-X5 GNSS receiver module. The integration process is segmented into three distinct stages. The first involves hardware integration, with an illustrative architecture diagram of the real-time navigation system. Second, we focus on data preprocessing, where a cross-correlation approach is proposed to tackle multi-sensor time synchronization issues, specifically to determine potential time lags in IMU data. The final phase covers the fusion of multi-sensor data and motion constraints. The Extended Kalman Filter (EKF) forms the backbone of this part, with Zero Velocity Update (ZUPT) and Non-Holonomic Constraints (NHC) being integrated into the Loosely Coupled (LC) scheme. Furthermore, the IMU calibration process is performed to ascertain necessary algorithmic parameters. Experimental results, conducted in diverse environments (open sky, GNSS challenging, and GNSS denied), will be presented in this paper. Comparisons with reference data indicate that the navigation accuracy of the developed integrated system, both in terms of hardware and navigation algorithm, achieves expected meter-level accuracy, fulfilling the \"Which Lane\" and \"Which Road\" level criteria in varied environments. Furthermore, outcomes from the GNSS denied environment align with predictions based on propagation error theory, demonstrating the feasibility of our navigation algorithm for tactical integrated navigation systems.