科研成果 by Year: 2017

Background: Coffee consumption has been associated with glucose metabolism and risk of type 2 diabetes.Objective: We examined whether the genetic variation determining habitual coffee consumption affected glycemic changes in response to weight-loss dietary intervention.Design: A genetic risk score (GRS) was calculated based on 8 habitual coffee consumption-associated single nucleotide polymorphisms. We used general linear models to test changes in glycemic traits in groups randomly assigned to high- and low-fat diets according to tertiles of the GRS.Results: We observed significant interactions between the GRS and low compared with high dietary fat intake on 6-mo changes in fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) (P-interaction = 0.023 and 0.022, respectively), adjusting for age, sex, race, physical activity, smoking, alcohol, seasonal variation, and baseline values of the respective outcomes. Participants with a higher GRS of habitual coffee consumption showed a greater reduction in fasting insulin and a marginally greater decrease in HOMA-IR in the low-fat diet intervention group.Conclusions: Our data suggest that participants with genetically determined high coffee consumption may benefit more by eating a low-fat diet in improving fasting insulin and HOMA-IR in a short term. This trial was registered at clinicaltrials.gov as NCT00072995 and NCT03258203.

Context: Adiponectin plays key roles in regulating appetite and food intake. Objective: To investigate interactions between the genetic risk score (GRS) for adiponectin levels and weight-loss diets varying in macronutrient intake on long-term changes in appetite and adiponectin levels. Design, Setting, and Participants: A GRS was calculated based on 5 adiponectin-associated variants in 692 overweight adults from the 2-year Preventing Overweight Using Novel Dietary Strategies trial. Main Outcome Measures: Repeated measurements of plasma adiponectin levels and appetite-related traits, including cravings, fullness, prospective consumption, and hunger. Results: Dietary fat showed nominally significant interactions with the adiponectin GRS on changes in appetite score and prospective consumption from baseline to 6 months (P for interaction = 0.014 and 0.017, respectively) after adjusting for age, sex, ethnicity, baseline body mass index, and baseline respective outcome values. The GRS for lower adiponectin levels was associated with a greater decrease in appetite (P < 0.001) and prospective consumption (P = 0.008) among participants consuming a high-fat diet, whereas no significant associations were observed in the low-fat group. Additionally, a significant interaction was observed between the GRS and dietary fat on 6-month changes in adiponectin levels (P for interaction = 0.021). The lower GRS was associated with a greater increase in adiponectin in the low-fat group (P = 0.02), but it was not associated with adiponectin changes in the high-fat group (P = 0.31). Conclusions: Our findings suggest that individuals with varying genetic architecture of circulating adiponectin may respond divergently in appetite and adiponectin levels to weight-loss diets varying in fat intake.

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

Genomic mosaicism in parental gametes and peripheral tissues is an important consideration for genetic counseling. We studied a Chinese cohort affected by a severe epileptic disorder, Dravet syndrome (DS). There were 56 fathers who donated semen and 15 parents who donated multiple peripheral tissue samples. We used an ultra-sensitive quantification method, micro-droplet digital PCR (mDDPCR), to detect parental mosaicism of the proband’s pathogenic mutation in SCN1A, the causal gene of DS in 112 families. Ten of the 56 paternal sperm samples were found to exhibit mosaicism of the proband’s mutations, with mutant allelic fractions (MAFs) ranging from 0.03% to 39.04%. MAFs in the mosaic fathers’ sperm were significantly higher than those in their blood (p = 0.00098), even after conditional probability correction (p’ = 0.033). In three mosaic fathers, ultra-low fractions of mosaicism (MAF < 1%) were detected in the sperm samples. In 44 of 45 cases, mosaicism was also observed in other parental peripheral tissues. Hierarchical clustering showed that MAFs measured in the paternal sperm, hair follicles and urine samples were clustered closest together. Milder epileptic phenotypes were more likely to be observed in mosaic parents (p = 3.006e-06). Our study provides new insights for genetic counseling.

Spatial patterns and temporal trends of nitrogen (N) and phosphorus (P) deposition are important for quantifying their impact on forest carbon (C) uptake. In a first step, we modeled historical and future change in the global distributions of the atmospheric deposition of N and P from the dry and wet deposition of aerosols and gases containing N and P. Future projections were compared between two scenarios with contrasting aerosol emissions. Modeled fields of N and P deposition and P concentration were evaluated using globally distributed in situ measurements. N deposition peaked around 1990 in European forests and around 2010 in East Asian forests, and both increased sevenfold relative to 1850. P deposition peaked around 2010 in South Asian forests and increased 3.5-fold relative to 1850. In a second step, we estimated the change in C storage in forests due to the fertilization by deposited N and P (Delta C-v (dep)), based on the retention of deposited nutrients, their allocation within plants, and C:N and C:P stoichiometry. Delta C-v (dep) for 1997-2013 was estimated to be 0.27 +/- 0.13 Pg C year(-1) from N and 0.054 +/- 0.10 Pg C year(-1) from P, contributing 9% and 2% of the terrestrial C sink, respectively. Sensitivity tests show that uncertainty of Delta C-v (dep) was larger from P than from N, mainly due to uncertainty in the fraction of deposited P that is fixed by soil. Delta C-P (dep) was exceeded by Delta C-N (dep) over 1960-2007 in a large area of East Asian and West European forests due to a faster growth in N deposition than P. Our results suggest a significant contribution of anthropogenic P deposition to C storage, and additional sources of N are needed to support C storage by P in some Asian tropical forests where the deposition rate increased even faster for P than for N.

The increasing demand of livestock products and production efficiency of livestock husbandry, and restoration of grassland ecosystem have been inducing the rapid transition of livestock husbandry systems from pastoralism into intensive systems. Such transition has been resulted in changes in the greenhouse gas (GHG) emissions, though it is rarely studied, especially in the pastoral area of China. Aimed to address this question, on the Qinghai-Tibet Plateau we selected Chanaihai village as the pastoralism system, and Guinan Grassland Development Limited Company as the combination of extensive and intensive livestock husbandry system, to compare the GHG emission between the two systems using life cycle assessment method. Our results showed that the GHG emission intensity both in per unit of area and per unit of carcass weight in the combined extensive/intensive livestock husbandry were higher than the pastoralism, indicating that the shift into the combined extensive/intensive livestock husbandry system increased the GHG emission. Such results could be attributed to the lower soil carbon uptake and higher GHG emission derived from the external inputs such as seed, diesel, and electricity in the combined extensive/intensive system. These findings demonstrated that the ongoing transition in the pastoral area of Qinghai-Tibet Plateau may be inappropriate Under the background of global GHG mitigation. As suggestions, we argued that reduction in the manure combustion and increase in soil carbon uptake could be effective measures to reduce the GHG emission intensity of livestock husbandry. (C) 2017 Elsevier Ltd. All rights reserved.

AimsThe aim of this guide is to provide practical help for ecologists who analyze data from biodiversity–ecosystem functioning experiments. Our approach differs from others in the use of least squares-based linear models (LMs) together with restricted maximum likelihood-based mixed models (MMs) for the analysis of hierarchical data. An original data set containing diameter and height of young trees grown in monocultures, 2- or 4-species mixtures under ambient light or shade is used as an example.MethodsStarting with a simple LM, basic features of model fitting and the subsequent analysis of variance (ANOVA) for significance tests are summarized. From this, more complex models are developed. We use the statistical software R for model fitting and to demonstrate similarities and complementarities between LMs and MMs. The formation of contrasts and the use of error (LMs) or random-effects (MMs) terms to account for hierarchical data structure in ANOVAs are explained.Important FindingsData from biodiversity experiments can be analyzed at the level of entire plant communities (plots) and plant individuals. The basic explanatory term is species composition, which can be divided into contrasts in many ways depending on specific biological hypotheses. Typically, these contrasts code for aspects of species richness or the presence of particular species. For significance tests in ANOVAs, contrast terms generally are compared with remaining variation of the explanatory terms from which they have been ‘carved out’. Once a final model has been selected, parameters (e.g. means or slopes for fixed-effects terms and variance components for error or random-effects terms) can be estimated to indicate the direction and size of effects.

BACKGROUND: Whether habitual coffee consumption interacts with the genetic predisposition to obesity in relation to body mass index (BMI) and obesity is unknown. METHODS: We analyzed the interactions between genetic predisposition and habitual coffee consumption in relation to BMI and obesity risk in 5116 men from the Health Professionals Follow-up Study (HPFS), in 9841 women from the Nurses' Health Study (NHS), and in 5648 women from the Women's Health Initiative (WHI). The genetic risk score was calculated based on 77 BMI-associated loci. Coffee consumption was examined prospectively in relation to BMI. RESULTS: The genetic association with BMI was attenuated among participants with higher consumption of coffee than among those with lower consumption in the HPFS (P interaction = 0.023) and NHS (P interaction = 0.039); similar results were replicated in the WHI (P interaction = 0.044). In the combined data of all cohorts, differences in BMI per increment of 10-risk allele were 1.38 (standard error (SE), 0.28), 1.02 (SE, 0.10), and 0.95 (SE, 0.12) kg/m(2) for coffee consumption of < 1, 1-3 and > 3 cup(s)/day, respectively (P interaction < 0.001). Such interaction was partly due to slightly higher BMI with higher coffee consumption among participants at lower genetic risk and slightly lower BMI with higher coffee consumption among those at higher genetic risk. Each increment of 10-risk allele was associated with 78% (95% confidence interval (CI), 59-99%), 48% (95% CI, 36-62%), and 43% (95% CI, 28-59%) increased risk for obesity across these subgroups of coffee consumption (P interaction = 0.008). From another perspective, differences in BMI per increment of 1 cup/day coffee consumption were 0.02 (SE, 0.09), -0.02 (SE, 0.04), and -0.14 (SE, 0.04) kg/m(2) across tertiles of the genetic risk score. CONCLUSIONS: Higher coffee consumption might attenuate the genetic associations with BMI and obesity risk, and individuals with greater genetic predisposition to obesity appeared to have lower BMI associated with higher coffee consumption.

Naturally occurring nucleos(t)ide analogue resistance (NUCr) substitution frequencies in the reverse transcriptase (RT) of the hepatitis B virus (HBV) were studied extensively after the clinical approval of nucleos(t)ide analogues (NUCs; year of approval 1998). We aimed to study NUCr substitutions in HBV RT sequences obtained before 1998 and better understand the evolution of RT sequences without NUC pressures. Our strategy was to retrieve HBV sequences from GenBank deposited before 1998. The initial search used the keywords "hepatitis B virus" or "HBV" and 1139 sequences were found. Data analyses included information extraction: sequence quality control and amino acid substitution analysis on 8 primary NUCr and 3 secondary substitution codons. Three hundred and ninety-four RT-containing sequences of 8 genotypes from 25 countries in 4 continents were selected. Twenty-seven (6.9%) sequences were found to harbor substitutions at NUCr-related codons. Secondary substitutions (rtL80V and rtV173G/A/L) occurred more frequently than primary NUCr substitutions (rtI169L; rtA181G; T184A/S; rtS202T/R; rtM204L and rtM250K). Typical amino acid substitutions associated with NUCr were of rtL80V, rtV173L and rtT184A/S. We confirm the presence of naturally occurring typical HBV NUCr substitutions with very low frequencies, and secondary substitutions are more likely to occur than primary NUCr substitutions without the selective pressure of NUCs. Keywords: hepatitis B virus; naturally occurring; nucleos(t)ides analogue resistance; pre-existing; reverse transcriptase; substitution.