Hundreds of variants clustered in genomic loci and biological pathways affect human height

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.

Macroscopic Neat Single-Walled Carbon Nanotubes Fibers

The first-ever well-aligned continuous macroscopic neat single-walled carbon nanotube (SWNT) fibers were produced using conventional spinning techniques. Neat SWNT fibers, containing no surfactant or polymer, were made by spinning dispersions of SWNTs in 102% sulfuric acid into different coagulants. The critical role of sulfuric acid in dispersing and aligning SWNTs during fiber formation has been explored. Characterization shows alignment greater than any other macroscopic neat SWNT material reported to-date while providing insight into the fundamental hierarchy and nature of SWNT fiber formation. Electrical, thermal, and mechanical measurements indicate that neat SWNT fibers hold tremendous potential for future applications

Latitudinal differences in early growth of largehead hairtail (Trichiurus japonicus) in relation to environmental variables

Largehead hairtail (Trichiurus japonicus) in the China Seas shows an increasing catch trend, despite continued overexploitation, which could be attributed to improved recruitment as a result of strengthened early growth. To understand the early growth variability of largehead hairtail, we examined the linkages between early growth, as revealed by otolith microstructure, and the associated environmental variables over both spatial and temporal scales. Young‐of‐the‐Year largehead hairtail were collected from three regions in the Bohai, Yellow and East China Seas between 29° and 39° N. Daily increment widths of sagittal otoliths were measured and used as a proxy for somatic growth. We found two spawning cohorts, Spring‐ and Summer‐spawned cohorts, that showed latitudinal differences in both mean growth and growth pattern. The transition time from larval to juvenile stage was identified at around 40 days. Daily increment widths of two cohorts showed similar growth pattern in the first 40 days, while location had a marked effect on daily growth over 41–110 days. This suggests physiologically constrained growth pattern in larval stage, but more plastic growth subject to habitat‐specific influences in juvenile stage. The gradient forest analysis identified sea bottom temperature, vertical temperature gradient, and sea surface salinity, as the most important variables in determining early growth. Latitudinal differences in early growth pattern and their response to environmental variables suggest adaptive plasticity of early growth, which has notable implication for the management and sustainable utilization of this important but heavily exploited resource in the China Seas.acceptedVersio

Factors associated with health-seeking behavior among migrant workers in Beijing, China

<p>Abstract</p> <p>Background</p> <p>Migrant workers are a unique phenomenon in the process of China's economic transformation. The household registration system classifies them as temporary residents in cities, putting them in a vulnerable state with an unfair share of urban infrastructure and social public welfare. The amount of pressure inflicted by migrant workers in Beijing, as one of the major migration destinations, is currently at a threshold. This study was designed to assess the factors associated with health-seeking behavior and to explore feasible solutions to the obstacles migrant workers in China faced with when accessing health-care.</p> <p>Methods</p> <p>A sample of 2,478 migrant workers in Beijing was chosen by the multi-stage stratified cluster sampling method. A structured questionnaire survey was conducted via face-to-face interviews between investigators and subjects. The multilevel methodology (MLM) was used to demonstrate the independent effects of the explanatory variables on health seeking behavior in migrant workers.</p> <p>Results</p> <p>The medical visitation rate of migrant workers within the past two weeks was 4.8%, which only accounted for 36.4% of those who were ill. Nearly one-third of the migrant workers chose self-medication (33.3%) or no measures (30.3%) while ill within the past two weeks. 19.7% of the sick migrants who should have been hospitalized failed to receive medical treatment within the past year. According to self-reported reasons, the high cost of health service was a significant obstacle to health-care access for 40.5% of the migrant workers who became sick. However, 94.0% of the migrant workers didn't have any insurance coverage in Beijing. The multilevel model analysis indicates that health-seeking behavior among migrants is significantly associated with their insurance coverage. Meanwhile, such factors as household monthly income per capita and working hours per day also affect the medical visitation rate of the migrant workers in Beijing.</p> <p>Conclusion</p> <p>This study assesses the influence of socio-demographic characteristics on the migrant workers' decision to seek health care services when they fall ill, and it also indicates that the current health service system discourages migrant workers from seeking appropriate care of good quality. Relevant policies of public medical insurance and assistance program should be vigorously implemented for providing affordable health care services to the migrants. Feasible measures need to be taken to reduce the health risks associated with current hygiene practices and equity should be assured in access to health care services among migrant workers.</p

The Na(+)/Ca(2+) exchanger NCKX4 governs termination and adaptation of the mammalian olfactory response

Sensory perception requires accurate encoding of stimulus information by sensory receptor cells. We identified NCKX4, a potassium-dependent Na(+)/Ca(2+) exchanger, as being necessary for rapid response termination and proper adaptation of vertebrate olfactory sensory neurons (OSNs). Nckx4(-/-) (also known as Slc24a4) mouse OSNs displayed substantially prolonged responses and stronger adaptation. Single-cell electrophysiological analyses revealed that the majority of Na(+)-dependent Ca(2+) exchange in OSNs relevant to sensory transduction is a result of NCKX4 and that Nckx4(-/-) mouse OSNs are deficient in encoding action potentials on repeated stimulation. Olfactory-specific Nckx4(-/-) mice had lower body weights and a reduced ability to locate an odorous source. These results establish the role of NCKX4 in shaping olfactory responses and suggest that rapid response termination and proper adaptation of peripheral sensory receptor cells tune the sensory system for optimal perception

Precore Mutation of Hepatitis B Virus May Contribute to Hepatocellular Carcinoma Risk: Evidence from an Updated Meta-Analysis

BACKGROUND: Studies focused on the correlation of mutations in the genome of Hepatitis B Virus (HBV) like Pre-S mutation, Basal Core promoter (BCP), Enhancer II (EnhII), especially Precore mutation, with the risk of hepatocellular carcinoma (HCC) have triggered stiff controversies. With an increasing number of studies in this field recently, we conducted this meta-analysis to appraise the correlations. METHODS: We searched the commonly used databases both in English and Chinese till February 1(st), 2012. Meta-analysis was performed in fixed/random-effects models using STATA 10.0. Publication bias was examined through Egger's test and Begg's funnel plot. RESULTS: In total, 85 case-control studies were included involving 16745 HBV-infected patients, of whom 5781 had HCC. Statistically significant correlations were observed in Precore mutation G1896A (OR = 1.46, 95% confidence interval [CI] = 1.15-1.85, P(OR) = 0.002), G1899A (OR = 3.13, 95%CI = 2.38-4.13, P(OR)<0.001) and Pre-S mutation especially Pre-S1 deletion (OR = 2.94, 95%CI = 2.22 to 3.89) and Pre-S2 deletion (OR = 3.02, 95%CI = 2.03 to 4.50). Similar correlation existed between BCP double mutation A1762T/G1764A, T1753V, C1653T and HCC. In subgroup analysis, the Asians, genotype C or HBeAg positive patients with certain above mutations may be more susceptible to HCC. Besides, the mutations like G1896A and BCP double mutation may be associated with the progression of the liver diseases. CONCLUSIONS: Precore mutation G1896A, G1899A, deletions in Pre-S region as well as the other commonly seen mutations correlated with the increased risk of HCC, especially in Asians and may predict the progression of the liver disease