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The human face is a heritable surface with many complex sensory organs. In recent years, many genetic loci associated with facial features have been reported in different populations, yet there is a lack of studies on the Han Chinese population. Here, we report a genome-wide association study of 3D normal human faces of 2,659 Han Chinese with autosegment phenotypes of facial morphology. We identify single-nucleotide polymorphisms (SNPs) encompassing four genomic regions showing significant associations with different facial regions, including SNPs in DENND1B associated with the chin, SNPs among PISRT1 associated with eyes, SNPs between DCHS2 and SFRP2 associated with the nose, and SNPs in VPS13B associated with the nose. We replicate 24 SNPs from previously reported genetic loci in different populations, whose candidate genes are DCHS2, SUPT3H, HOXD1, SOX9, PAX3, and EDAR. These results provide a more comprehensive understanding of the genetic basis of variation in human facial morphology.

The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people1,2. Here we report genome-wide data from 166 East Asian individuals dating to between 6000 bc and ad 1000 and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan Plateau are linked by a deeply splitting lineage that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 bc), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 bc) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet—where it forms approximately 84% of the gene pool in some groups—and to the Central Plain, where it has contributed around 59–84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 bc to ad 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai–Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 bc but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 bc with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan. Genome-wide data from 166 East Asian individuals dating to between 6000 bc and ad 1000 and from 46 present-day groups provide insights into the histories of mixture and migration of human populations in East Asia.

Facial and cranial variation represent a multidimensional set of highly correlated and heritable phenotypes. Little is known about the genetic basis explaining this correlation. We develop a software package ALoSFL for simultaneous localization of facial and cranial landmarks from head computed tomography (CT) images, apply it in the analysis of head CT images of 777 Han Chinese women, and obtain a set of phenotypes representing variation in face, skull and facial soft tissue thickness (FSTT). Association analysis of 301 single nucleotide polymorphisms (SNPs) from 191 distinct genomic loci previously associated with facial variation reveals an unexpected larger number of loci showing significant associations (P 1e-3) with cranial phenotypes than expected under the null (O/E = 3.39), suggesting facial and cranial phenotypes share a substantial proportion of genetic components. Adding FSTT to a SNP-only model shows a large impact in explaining facial variance. A gene ontology analysis reveals that bone morphogenesis and osteoblast differentiation likely underlie our cranial-significant findings. Overall, this study simultaneously investigates the genetic effects on both facial and cranial variation of the same sample, supporting that facial variation is a composite phenotype of cranial variation and FSTT.

In an arid and semi-arid irrigation district, water-saving practices are essential for the sustainable use of water resources. The Soil and Water Assessment Tool (SWAT) was used to simulate hydrological processes under three water-saving scenarios for the Jinghui Canal irrigation district (JCID) in Northwest China. Due to the lack of available hydrometric stations in the study area, the model was calibrated by Moderate Resolution Imaging Spectroradiometer Global Evaporation (MOD16) from 2001 to 2010 on monthly scale. The simulation results showed that using MOD16 to calibrate the SWAT model was an alternative approach when hydro-meteorological data were lacking. It also revealed that the annual average surface runoff (SURQ) decreased by 4.13%, 8.37% and 12.08% and the percolation (PERC) increased by 3.67%, 7.59% and 11.19%, with the improvement of the water-saving degree (the effective utilization coefficient of irrigation water (EUCIW) increased by 0.1, 0.2 and 0.3). Compared with the above two components, the change in actual evapotranspiration (ET) was not obvious. From the perspective of the spatial scale, the changes in every component in the east regions were generally greater than those in the west regions. On a monthly scale, the change in every component was mainly during these two periods. The analysis results of water balance in the study area showed that the proportion of SURQ in water balance decreased (from 14.02% to 12.33%), while that of PERC increased (from 10.99% to 12.22%) after the application of the water-saving irrigation. The decrease in the variation in soil water content indicates that the improvement of the water-saving degree plays a positive role in maintaining the sustainable development of water resources in irrigated areas. This study demonstrates the potential to use remotely sensed evapotranspiration data for hydrological model calibration and validation in a sparsely gauged region with reasonable accuracy. The results of this study also provide a reference for the effect of water-saving irrigation in the irrigated area.

Facial morphology, the most conspicuous feature of human appearance, is highly heritable. Previous studies on the genetic basis of facial morphology were mainly performed in European populations. Applying a proven data-driven phenotyping and multivariate genome-wide scanning protocol to the largest collection of 3D facial images of an East Asian population to date, we identified 244 leading variants associated with normal-range facial variation, of which 130 are novel. A newly proposed polygenic shape analysis indicates that the effects of the variants on East Asian facial shape can be generalized into the European population. Based on this analysis, we further identified 13 variants mainly related to differences between European and East Asian facial shape. Natural selection analyses suggest that the difference in European and East Asian nose shape is caused by a directional selection, mainly due to a local adaptation in Europeans. Our results expand the knowledge of human facial genetics and illustrates for the first time the underlying genetic basis for facial differences across populations.

Objectives The Hui people are the adherents of Muslim faith and distributing throughout China. There are two contrasting hypotheses about the origin and diversification of the Hui people, namely, the demic diffusion involving the mass movement of people or simple cultural diffusion. Materials and methods We collected 621 unrelated male individuals from 23 Hui populations all over China. We comprehensively genotyped more than 100 informative Y-chromosomal single nucleotide polymorphisms and 17 Y-chromosomal short tandem repeats (STRs) on those samples. Results Co-analyzed with published worldwide populations, our results suggest the origin of Hui people has involved massive assimilation of indigenous East Asians with about 70% in total of the paternal ancestry could be traced back to East Asia and the left 30% to various regions in West Eurasia. Discussion The genetic structure of the extant Hui populations was primarily shaped by the indigenous East Asian populations as they contribute the majority part of the paternal lineages of Hui people. The West Eurasian admixture was probably a sex-biased male-driven process since we have not found such a high proportion of West Eurasian gene flow on autosomal STRs and maternal mtDNA.

In many densely populated urban areas, artificial lakes have replaced natural river systems as water sources to provide people with water for living and industrial production. However, groundwater mounding due to seepage from water storage facilities will have an impact on the regional groundwater flow regime. This study investigated the effects of the construction and operation of the Doumen Reservoir in northwestern China on the local groundwater flow regime. Groundwater level variations before the construction of the impoundment were analyzed by wavelet analysis and indicated that most of the observed variations in levels were due to changes in groundwater abstraction in the area. Data were collected from drilling and real-time monitoring; a coupled Hydrus-1D and MODFLOW model was developed to simulate the impact of water storage on the surrounding groundwater environment. The simulation results show that compared with the initial flow field, the maximum elevation of the groundwater mound that would develop beneath water storage structured in the area would vary between about 4.9 and 6.9 m. Compared with the impoundment of the test section, other modeled scenarios will cause varying degrees of groundwater mounding around the reservoir area but no flooding of existing infrastructure is predicted to take place. The predicted seepage rate from the facility is 3660 m3/day, and anti-seepage measures are recommended to limit the effects of groundwater mounding.

The deep population history of East Asia remains poorly understood due to a lack of ancient DNA data and sparse sampling of present-day people. We report genome-wide data from 191 individuals from Mongolia, northern China, Taiwan, the Amur River Basin and Japan dating to 6000 BCE – 1000 CE, many from contexts never previously analyzed with ancient DNA. We also report 383 present-day individuals from 46 groups mostly from the Tibetan Plateau and southern China. We document how 6000-3600 BCE people of Mongolia and the Amur River Basin were from populations that expanded over Northeast Asia, likely dispersing the ancestors of Mongolic and Tungusic languages. In a time transect of 89 Mongolians, we reveal how Yamnaya steppe pastoralist spread from the west by 3300-2900 BCE in association with the Afanasievo culture, although we also document a boy buried in an Afanasievo barrow with ancestry entirely from local Mongolian hunter-gatherers, representing a unique case of someone of entirely non-Yamnaya ancestry interred in this way. The second spread of Yamnaya-derived ancestry came via groups that harbored about a third of their ancestry from European farmers, which nearly completely displaced unmixed Yamnaya-related lineages in Mongolia in the second millennium BCE, but did not replace Afanasievo lineages in western China where Afanasievo ancestry persisted, plausibly acting as the source of the early-splitting Tocharian branch of Indo-European languages. Analyzing 20 Yellow River Basin farmers dating to ∼3000 BCE, we document a population that was a plausible vector for the spread of Sino-Tibetan languages both to the Tibetan Plateau and to the central plain where they mixed with southern agriculturalists to form the ancestors of Han Chinese. We show that the individuals in a time transect of 52 ancient Taiwan individuals spanning at least 1400 BCE to 600 CE were consistent with being nearly direct descendants of Yangtze Valley first farmers who likely spread Austronesian, Tai-Kadai and Austroasiatic languages across Southeast and South Asia and mixing with the people they encountered, contributing to a four-fold reduction of genetic differentiation during the emergence of complex societies. We finally report data from Jomon hunter-gatherers from Japan who harbored one of the earliest splitting branches of East Eurasian variation, and show an affinity among Jomon, Amur River Basin, ancient Taiwan, and Austronesian-speakers, as expected for ancestry if they all had contributions from a Late Pleistocene coastal route migration to East Asia.

Human face is a heritable surface with many complex sensory organs. In recent years, many genetic loci associated with facial features have been reported in different populations, yet there is a lack for the Han Chinese population. We report a genome-wide association analysis of 3D normal human faces in 2659 Han Chinese with two groups of phenotypes, the partial and whole face phenotypes and the distance and angle phenotypes. We found significant signals in five genomic regions with traits related to nose or eyes, including rs970797 in 2q31.1 near HOXD1 and MTX2, rs16897517 in 8q22.2 at intron of VPS13B, rs9995821 in 4q31.3 near DCHS2 and SFRP2, rs12636297 in 3q23 near PISRT1, and rs12948076 in 17q24.3 near SOX9 and CASC17. We visualized changes in facial morphology by comparing the volume of local areas and observed that these nose-related loci were associated with different features of the nose, including nose prominence, nasion height, and nostril shape, suggesting that the nose underlies precise genetic regulation. These results provide a more comprehensive understanding of the relationship between genetic loci and human facial morphology.Author SummaryHuman face as a combination of delicate sensory organs has a strong genetic component, as evidenced by the identical appearance in twins and shared facial features in close relatives. Although facial genetics have been studied in different populations, our knowledge between genetic markers with facial features is still limited. In this paper, we found genetic variants associated with nose and eyes through a large-scale high-resolution 3D facial genetic study on the Han Chinese population. We observed that these nose-related loci were associated with different features of the nose, including nose prominence, nasion height, and nostril shape, which suggests the nose underlies precise genetic regulation. Intriguingly, we noted that genes (DCHS2 and SFRP2) related to one of these loci are differentially expressed in human and chimp cranial neural crest cells, which plays a crucial role in the early formation of facial morphology. The ongoing genetic studies of facial morphology will improve our understanding of human craniofacial development, and provide potential evolution evidence of human facial features.

Hair straightness/curliness is one of the most conspicuous features of human variation and is particularly diverse among populations. A recent genome-wide scan found common variants in the Trichohyalin (TCHH) gene that are associated with hair straightness in Europeans, but different genes might affect this phenotype in other populations. By sampling 2899 Han Chinese, we performed the first genome-wide scan of hair straightness in East Asians, and found EDAR (rs3827760) as the predominant gene (P = 4.67 × 10−16), accounting for 3.66 % of the total variance. The candidate gene approach did not find further significant associations, suggesting that hair straightness may be affected by a large number of genes with subtle effects. Notably, genetic variants associated with hair straightness in Europeans are generally low in frequency in Han Chinese, and vice versa. To evaluate the relative contribution of these variants, we performed a second genome-wide scan in 709 samples from the Uyghur, an admixed population with both eastern and western Eurasian ancestries. In Uyghurs, both EDAR (rs3827760: P = 1.92 × 10−12) and TCHH (rs11803731: P = 1.46 × 10−3) are associated with hair straightness, but EDAR (OR 0.415) has a greater effect than TCHH (OR 0.575). We found no significant interaction between EDAR and TCHH (P = 0.645), suggesting that these two genes affect hair straightness through different mechanisms. Furthermore, haplotype analysis indicates that TCHH is not subject to selection. While EDAR is under strong selection in East Asia, it does not appear to be subject to selection after the admixture in Uyghurs. These suggest that hair straightness is unlikely a trait under selection.

Maxillary sinus disease is frequently observed in patients with unilateral cleft lip and palate (UCLP). The anatomical variations of maxillary sinus and maxilla may play a role in the high incidence of sinusitis. The aims of this study were to evaluate and compare the three-dimensional (3D) structural features of maxillary sinus and maxilla in UCLP adolescent patients between the defect and non-defect sides, and investigate the morphological relationship between the maxillary sinus and maxilla on the defect side by using cone-beam computed tomography (CBCT).CBCT images were acquired from 42 UCLP adolescent patients. Maxillary sinus and maxilla on the defect and non-defect sides were segmented respectively and assessed three dimensionally, and the comparison was performed by paired t-test. A multiple linear regression was conducted to investigate the morphological relationship between the maxillary sinus and maxilla on the defect side.No statistically significant difference was observed in any parameter of the maxillary sinus between the defect and non-defect sides (P 0.05). Significant differences were observed in the length, anterior width, anterior height, and volume of the maxilla between the defect side and non-defect sides (P 0.05). The parameters of maxillary sinus were significant related to the posterior width and height of maxilla on the defect side.Adolescent patients with UCLP present similar 3D structural features of the maxillary sinus on both sides. Significant differences of the maxilla between the defect and non-defect sides were displayed in the area adjacent to the defect but not showed in the posterior portion of maxilla. Certain structures of the posterior portion of maxilla contribute to the variability of maxillary sinus.

Mechanosensitive ion channels such as Piezo, TRAAK, TRPs and OSCA are important transmembrane proteins that are involved in many physiological processes such as touch, hearing and blood pressure regulation. Unlike ligand-gated channels or voltage-gated ion channels, which have a canonical ligand-binding domain or voltage-sensing domain, the mechanosensitive domain and related gating mechanism remain elusive. TRAAK channels are mechanosensitive channels that convert a physical mechanical force into a flow of potassium ions. The structures of TRAAK channels have been solved, however, the functional roles of the structural domains associated with channel mechanosensitivity remains unclear. Here, we generated a series of chimeric mutations between TRAAK and a non-mechanosensitive silent TWIK-1 K2P channel. We found that the selectivity filter region functions as the major gate of outward rectification and found that lower part of fourth transmembrane domain (M4) is necessary for TRAAK channel mechanosensitivity. We further demonstrated that upper part of M4 can modulate the mechanosensitivity of TRAAK channel. Furthermore, we found that hydrophilic substitutions of W262 and F121 facing each other, and hydrophobic substitutions of Q258 and G124, which are above and below W262 and F121, respectively, greatly increase mechanosensitivity, which suggests that dynamic interactions in the upper part of M4 and PH1 domain are involved in TRAAK channel mechanosensitivity. Interestingly, these gain-of-function mutations are sensitive to cell-poking stimuli, indicating that cell-poking stimuli generate a low membrane mechanical force that opens TRAAK channels. Our results thus showed that fourth transmembrane domain of TRAAK is critical for the gating of TRAAK by mechanical force and suggested that multiple dynamic interactions in the upper part of M4 and PH1 domain are involved in this process.

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10−10) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10−8). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10−11) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure., Author summary Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here we performed genome-wide association studies for eyebrow thickness in multiple ethnic groups, including Han Chinese, Uyghurs, Latin Americans, and Caucasians. We found solid evidence that novel genetic variants near the SOX2, FOXD1 and EDAR genes could affect eyebrow thickness. After fine mapping, we prioritized four variants for experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that the variants rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes. This represents a successful example of a combination of GWAS and CRISPR/Cas9 technology to demonstrate how non-coding variants with regulatory functions may play an important role in common diseases and traits. Finally, suitable statistical analyses suggest that, contrary to popular speculation, eyebrow thickness should not be subject to strong selection pressure, including sexual selection.

Traffic-related air pollution is known to be associated with skin aging manifestations. We previously found that the use of fossil fuels was associated with skin aging, but no direct link between indoor air pollutants and skin aging manifestations has ever been shown. Here we directly measured the indoor PM2.5 exposure in 30 households in Taizhou, China. Based on the directly measured PM2.5 exposure and questionnaire data of indoor pollution sources, we built a regression model to predict the PM2.5 exposure in larger datasets including an initial examination group (N = 874) and a second examination group (N = 1003). We then estimated the association between the PM2.5 exposure and skin aging manifestations by linear regression. In the initial examination group, we showed that the indoor PM2.5 exposure levels were positively associated with skin aging manifestation, including score of pigment spots on forehead (12.5% more spots per increase of IQR, P-value 0.0371), and wrinkle on upper lip (7.7% more wrinkle on upper lip per increase of IQR, P-value 0.0218). The results were replicated in the second examination group as well as in the pooled dataset. Our study provided evidence that the indoor PM2.5 exposure is associated with skin aging manifestation in a Chinese population.

The Y chromosome is one of the best genetic materials to explore the evolutionary history of human populations. Global analyses of Y chromosomal short tandem repeats (STRs) data can reveal very interesting world population structures and histories. However, previous Y-STR works tended to focus on small geographical ranges or only included limited sample sizes. In this study, we have investigated population structure and demographic history using 17 Y chromosomal STRs data of 979 males from 44 worldwide populations. The largest genetic distances have been observed between pairs of African and non-African populations. American populations with the lowest genetic diversities also showed large genetic distances and coancestry coefficients with other populations, whereas Eurasian populations displayed close genetic affinities. African populations tend to have the oldest time to the most recent common ancestors (TMRCAs), the largest effective population sizes and the earliest expansion times, whereas the American, Siberian, Melanesian, and isolated Atayal populations have the most recent TMRCAs and expansion times, and the smallest effective population sizes. This clear geographic pattern is well consistent with serial founder model for the origin of populations outside Africa. The Y-STR dataset presented here provides the most detailed view of worldwide population structure and human male demographic history, and additionally will be of great benefit to future forensic applications and population genetic studies.

An adaptive variant of human Ectodysplasin receptor, EDARV370A, had undergone strong positive selection in East Asia. In mice and humans, EDARV370A was found to affect ectodermal-derived characteristics, including hair thickness, hair shape, active sweat gland density and teeth formation. Facial characteristics are also largely ectodermal derived. In this study, taking advantage of an admixed population of East Asian and European ancestry-the Uyghur, we aim to test whether EDARV370A is affecting facial characteristics and to investigate its pleiotropic nature and genetic model. In a sample of 1027 Uyghurs, we discover that EDARV370A is significantly associated with several facial characteristics, in particular shape of earlobe (P = 3.64 × 10 (-6) ) and type of chin (P = 9.23 × 10 (-5) ), with successful replication in other East Asian populations. Additionally, in this Uyghur population, we replicate previous association findings of incisors shoveling (P = 1.02 × 10 (-7) ), double incisors shoveling (P = 1.86 × 10 (-12) ) and hair straightness (P = 3.99 × 10 (-16) ), providing strong evidence supporting an additive model for the EDARV370A associations. Partial least square path model confirms EDARV370A systematically affect these weakly related ectodermal-derived characteristics, suggesting the pleiotropic effect of EDARV370A mainly plays roles in early embryo development. This study extends our knowledge about the pleiotropic nature of EDARV370A and provides potential clues to its adaptation fitness in human evolution.

Short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) are two kinds of commonly used markers in Y chromosome studies of forensic and population genetics. There has been increasing interest in the cost saving strategy by using the STR haplotypes to predict SNP haplogroups. However, the convergence of Y chromosome STR haplotypes from different haplogroups might compromise the accuracy of haplogroup prediction. Here, we compared the worldwide Y chromosome lineages at both haplogroup level and haplotype level to search for the possible haplotype similarities among haplogroups. The similar haplotypes between haplogroups B and I2, C1 and E1b1b1, C2 and E1b1a1, H1 and J, L and O3a2c1, O1a and N, O3a1c and O3a2b, and M1 and O3a2 have been found, and those similarities reduce the accuracy of prediction., Comment: 13 pages, 2 figures

The Qiangic languages in western Sichuan (WSC) are believed to be the oldest branch of the Sino-Tibetan linguistic family, and therefore, all Sino-Tibetan populations might have originated in WSC. However, very few genetic investigations have been done on Qiangic populations and no genetic evidences for the origin of Sino-Tibetan populations have been provided. By using the informative Y chromosome and mitochondrial DNA (mtDNA) markers, we analyzed the genetic structure of Qiangic populations. Our results revealed a predominantly Northern Asian-specific component in Qiangic populations, especially in maternal lineages. The Qiangic populations are an admixture of the northward migrations of East Asian initial settlers with Y chromosome haplogroup D (D1-M15 and the later originated D3a-P47) in the late Paleolithic age, and the southward Di-Qiang people with dominant haplogroup O3a2c1*-M134 and O3a2c1a-M117 in the Neolithic Age.