8 results
Cortical morphological heterogeneity of schizophrenia and its relationship with glutamatergic receptor variations
- Xuan Ouyang, Yunzhi Pan, Xudong Chen, Guowei Wu, Yixin Cheng, Wenjian Tan, Manqi Zhang, Mengjie Deng, Zhening Liu, Lena Palaniyappan
-
- Journal:
- European Psychiatry / Volume 66 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 09 May 2023, e38
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Recent genetic evidence implicates glutamatergic-receptor variations in schizophrenia. Glutamatergic excess during early life in people with schizophrenia may cause excitotoxicity and produce structural deficits in the brain. Cortical thickness and gyrification are reduced in schizophrenia, but only a subgroup of patients exhibits such structural deficits. We delineate the structural variations among unaffected siblings and patients with schizophrenia and study the role of key glutamate-receptor polymorphisms on these variations.
MethodsGaussian Mixture Model clustering was applied to the cortical thickness and gyrification data of 114 patients, 112 healthy controls, and 42 unaffected siblings to identify subgroups. The distribution of glutamate-receptor (GRM3, GRIN2A, and GRIA1) and voltage-gated calcium channel (CACNA1C) variations across the MRI-based subgroups was studied. The comparisons in clinical symptoms and cognition between patient subgroups were conducted.
ResultsWe observed a “hypogyric,” “impoverished-thickness,” and “supra-normal” subgroups of patients, with higher negative symptom burden and poorer verbal fluency in the hypogyric subgroup and notable functional deterioration in the impoverished-thickness subgroup. Compared to healthy subjects, the hypogyric subgroup had significant GRIN2A and GRM3 variations, the impoverished-thickness subgroup had CACNA1C variations while the supra-normal group had no differences.
ConclusionsDisrupted gyrification and thickness can be traced to the glutamatergic receptor and voltage-gated calcium channel dysfunction respectively in schizophrenia. This raises the question of whether MRI-based multimetric subtyping may be relevant for clinical trials of agents affecting the glutamatergic system.
Weight self-misperception and obesity-related knowledge, attitudes, lifestyle behaviours and cardio-metabolic markers among Chinese school-aged children and adolescents
- Jieyu Liu, Qi Ma, Xinxin Wang, Manman Chen, Tao Ma, Mengjie Cui, Jun Jiang, Yanhui Li, Di Gao, Ying Ma, Wen Yuan, Li Chen, Yi Zhang, Tongjun Guo, Jun Ma, Yanhui Dong
-
- Journal:
- Public Health Nutrition / Volume 26 / Issue 8 / August 2023
- Published online by Cambridge University Press:
- 24 April 2023, pp. 1549-1561
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Objective:
The relationships between childhood weight self-misperception and obesity-related factors particularly health markers have not been extensively discussed. This study aims to examine the associations between weight self-misperception and obesity-related knowledge, attitudes, lifestyles and cardio-metabolic markers among Chinese paediatric population.
Design:Cross-sectional study.
Setting:Data sourced from a national survey in Chinese seven provinces in 2013.
Participants:Children and adolescents aged 5–19 years.
Results:Of the total 14 079 participants, there were 14·5 % and 2·2 % participants over-estimated and under-perceived their weight, respectively. Multi-variable logistic regression was applied to calculate OR and 95 % CI (95 % Cl) of obesity-related behaviours and cardio-metabolic markers by actual and perceived weight status. Individuals who perceived themselves as overweight/obese were more likely to have prolonged screen time, insufficient dairy intake and over sugar-sweetened beverages consumption (all P < 0·05), regardless of their weight. Furthermore, actual overweight/obese individuals had higher odds of abnormal cardio-metabolic markers, but a smaller magnitude of association was found among weight under-estimators. Among non-overweight/obese individuals, weight over-estimation was positively associated with abdominal obesity (OR: 10·49, 95 % CI: 7·45, 14·76), elevated blood pressure (OR: 1·30, 95 % CI: 1·12, 1·51) and dyslipidemia (OR: 1·43, 95 % CI: 1·29, 1·58).
Conclusions:Weight over-perception was more prevalent than under-estimation, particularly in girls. Weight over-estimators tended to master better knowledge but behave more unhealthily; both weight over-perception and actual overweight/obesity status were associated with poorer cardio-metabolic markers. Future obesity intervention programmes should additionally pay attention to the population with inaccurate estimation of weight who were easily overlooked.
Inverse correlations between serum carotenoids and respiratory morbidity and mortality: the Third National Health and Nutrition Examination Survey
- Ruiming Yang, Ziteng Cao, Xin Liu, Mengjie Xiao, Mengyao Li, Yunyan Chen, Luyao Chen, Changhao Sun, Xia Chu, Qiang Ren, Wei Wei
-
- Journal:
- British Journal of Nutrition / Volume 130 / Issue 11 / 14 December 2023
- Published online by Cambridge University Press:
- 11 April 2023, pp. 1932-1941
- Print publication:
- 14 December 2023
-
- Article
- Export citation
-
The objective was to evaluate the association between serum carotenoid levels and respiratory morbidity and mortality in a nationally representative sample of US adults. We assessed the association of serum carotenoid levels with respiratory morbidity and mortality using logistic regression and proportional hazards regression models. Meanwhile, a series of confounders were controlled in regression models and restricted cubic spline, which included age, sex, race, marriage, education, income, drinking, smoking, regular exercise, BMI, daily energy intake, vitamin E, vitamin C, fruit intake, vegetable intake, diabetes, hypertension, asthma, emphysema and chronic bronchitis. Compared with participants in the lowest tertiles, participants in the highest tertiles of serum total carotenoids, β-cryptoxanthin and lutein/zeaxanthin levels had a significantly lower prevalence of emphysema (ORtotal carotenoids = 0·61, 95% CI: 0·41–0·89, ORβ-cryptoxanthin = 0·67, 95% CI: 0·49–0·92), chronic bronchitis (ORβ-cryptoxanthin = 0·66, 95% CI: 0·50–0·87) and asthma (Q2: ORlutein/zeaxanthin = 0·78, 95% CI: 0·62–0·97); participants in the highest tertiles of total carotenoids, α-carotene, lutein/zeaxanthin and lycopene had a lower risk of respiratory mortality (hazard ratio (HR)total carotenoids = 0·62, 95% CI: 0·42–0·90, HRα-carotene = 0·54, 95% CI: 0·36–0·82, HRlutein/zeaxanthin = 0·48, 95% CI: 0·33–0·71, HRlycopene = 0·66, 95% CI: 0·45–0·96) than those in the lowest tertiles. Higher serum total carotenoids and β-cryptoxanthin levels is associated with decreased prevalence of emphysema and chronic bronchitis, and higher serum total carotenoids, α-carotene, lutein/zeaxanthin and lycopene levels had a lower mortality of respiratory disease.
Velocity-defect laws, log law and logarithmic friction law in the convective atmospheric boundary layer
- Chenning Tong, Mengjie Ding
-
- Journal:
- Journal of Fluid Mechanics / Volume 883 / 25 January 2020
- Published online by Cambridge University Press:
- 26 November 2019, A36
-
- Article
- Export citation
-
The mean velocity profile in the convective atmospheric boundary layer (CBL) is derived analytically. The shear-stress budget equations and the mean momentum equations are employed in the derivation. The multi-point Monin–Obukhov similarity (MMO) recently proposed and analytically derived by Tong & Nguyen (J. Atmos. Sci., vol. 72, 2015, pp. 4337–4348) and Tong & Ding (J. Fluid Mech., vol. 864, 2019, pp. 640–669) provides the scaling properties of the statistics in the shear-stress budget equations. Our previous and present studies have shown that the CBL is mathematically a singular perturbation problem. Therefore, we obtain the mean velocity profile using the method of matched asymptotic expansions. Three scaling layers are identified: the outer layer, which includes the mixed layer, the inner-outer layer and the inner-inner layer, which includes the roughness layer. There are two overlapping layers, the local-free-convection layer and the log layer, respectively. Two new velocity-defect laws are discovered: the mixed-layer velocity-defect law and the surface-layer velocity-defect law. The local-free-convection mean profile is obtained by asymptotically matching the expansions in the first two layers. The log law is obtained by matching the expansions in the last two layers. The von Kármán constant is obtained using velocity and length scales, and therefore has a physical interpretation. A new friction law, the convective logarithmic friction law, is obtained. The present work provides an analytical derivation of the mean velocity profile hypothesized in the Monin–Obukhov similarity theory, and is part of a comprehensive derivation of the MMO scaling from first principles.
Multi-point Monin–Obukhov similarity in the convective atmospheric surface layer using matched asymptotic expansions
- Chenning Tong, Mengjie Ding
-
- Journal:
- Journal of Fluid Mechanics / Volume 864 / 10 April 2019
- Published online by Cambridge University Press:
- 11 February 2019, pp. 640-669
-
- Article
- Export citation
-
The multi-point Monin–Obukhov similarity (MMO) was recently proposed (Tong & Nguyen, J. Atmos. Sci., vol. 72, 2015, pp. 4337–4348) to address the issue of incomplete similarity in the framework of the original Monin–Obukhov similarity theory (MOST). MMO hypothesizes the following: (1) The surface-layer turbulence, defined to consist of eddies that are entirely inside the surface layer, has complete similarity, which however can only be represented by multi-point statistics, requiring a horizontal characteristic length scale (absent in MOST). (2) The Obukhov length $L$ is also the characteristic horizontal length scale; therefore, all surface-layer multi-point statistics, non-dimensionalized using the surface-layer parameters, depend only on the height and separations between the points, non-dimensionalized using $L$. However, similar to MOST, MMO was also proposed as a hypothesis based on phenomenology. In this work we derive MMO analytically for the case of the horizontal Fourier transforms of the velocity and potential temperature fluctuations, which are equivalent to the two-point horizontal differences of these variables, using the spectral forms of the Navier–Stokes and the potential temperature equations. We show that, for the large-scale motions (wavenumber $k<1/z$) in a convective surface layer, the solution is uniformly valid with respect to $z$ (i.e. as $z$ decreases from $z>-L$ to $z<-L$), where $z$ is the height from the surface. However, for $z<-L$ the solution is not uniformly valid with respective to $k$ as it increases from $k<-1/L$ to $k>-1/L$, resulting in a singular perturbation problem, which we analyse using the method of matched asymptotic expansions. We show that (1) $-L$ is the characteristic horizontal length scale, and (2) the Fourier transforms satisfy MMO with the non-dimensional wavenumber $-kL$ as the independent similarity variable. Two scaling ranges, the convective range and the dynamic range, discovered for $z\ll -L$ in Tong & Nguyen (2015) are obtained. We derive the leading-order spectral scaling exponents for the two scaling ranges and the corrections to the scaling ranges for finite ratios of the length scales. The analysis also reveals the dominant dynamics in each scaling range. The analytical derivations of the characteristic horizontal length scale ($L$) and the validity of MMO for the case of two-point horizontal separations provide strong support to MMO for general multi-point velocity and temperature differences.
Investigation of the pressure–strain-rate correlation and pressure fluctuations in convective and near neutral atmospheric surface layers
- Mengjie Ding, Khuong X. Nguyen, Shuaishuai Liu, Martin J. Otte, Chenning Tong
-
- Journal:
- Journal of Fluid Mechanics / Volume 854 / 10 November 2018
- Published online by Cambridge University Press:
- 31 August 2018, pp. 88-120
-
- Article
- Export citation
-
The pressure–strain-rate correlation and pressure fluctuations in convective and near neutral atmospheric surface layers are investigated. Their scaling properties, spectral characteristics, the contributions from the different source terms in the pressure Poisson equation and the effects of the wall are investigated using high-resolution (up to $2048^{3}$) large-eddy simulation fields and through spectral predictions. The pressure–strain-rate correlation was found to have the mixed-layer and surface-layer scaling in the strongly convective and near neutral atmospheric surface layers, respectively. Its apparent surface-layer scaling in the moderately convective surface layer is due to the slow variations of the mixed-layer contribution, and is an inherent problem for single-point statistics in a multi-scale surface layer. In the strongly convective surface layer the pressure spectrum has an approximate $k^{-5/3}$ scaling range for small wavenumbers ($kz\ll 1$) due to the turbulent–turbulent contribution, and does not follow the surface-layer scaling, where $k$ and $z$ are the horizontal wavenumber and the distance from the surface respectively. The pressure–strain-rate cospectrum components have a $k^{-1}$ scaling range, consistent with our prediction using the surface layer parameters. It is dominated by the buoyancy contribution. Thus the anisotropy in the surface layer is due to the energy redistribution caused by the density fluctuations of the large eddies, rather than the turbulent–turbulent (inertial) effects. In the near neutral surface layer, the turbulent–turbulent and rapid contributions are primarily responsible for redistribution of energy from the streamwise velocity component to the vertical and spanwise components, respectively. The pressure–strain-rate cospectra peak near $kz\sim 1$, and have some similarities to those in the strongly convective surface layer for $kz\ll 1$. For the moderately convective surface layer, the pressure–strain-rate cospectra change signs at scales of the order of the Obukhov length, thereby imposing it as a horizontal length scale in the surface layer. This result provides strong support to the multipoint Monin–Obukhov similarity recently proposed by Tong & Nguyen (J. Atmos. Sci., vol. 72, 2015, pp. 4337–4348). We further decompose the pressure into the free-space (infinite domain), the wall reflection and the harmonic contributions. In the strongly convective surface layer, the free-space contribution to the pressure–strain-rate correlation is dominated by the buoyancy part, and is the main cause of the surface-layer anisotropy. The wall reflection enhances the anisotropy for most of the surface layer, suggesting that the pressure source has a large coherence length. In the near neutral surface layer, the wall reflection is small, suggesting a much smaller source coherence length. The present study also clarifies the understanding of the role of the turbulent–turbulent pressure, and has implications for understanding the dynamics and structure as well as modelling the atmospheric surface layer.
3 - Introduction to statistical methods in genome-wide association studies
- from Part I - Genome-wide association studies
-
- By Can Yang, Hong Kong Baptist University, Cong Li, Yale University, Dongjun Chung, Yale University, Mengjie Chen, Yale University, Joel Gelernter, Yale University School of Medicine, Hongyu Zhao, Yale University
- Edited by Krishnarao Appasani
- Foreword by Stephen W. Scherer, Peter M. Visscher
-
- Book:
- Genome-Wide Association Studies
- Published online:
- 18 December 2015
- Print publication:
- 14 January 2016, pp 26-52
-
- Chapter
- Export citation
-
Summary
Introduction
After the completion of the Human Genome Project (Lander et al., 2001; Venter et al., 2001) and initiation of the International HapMap Project (Sachidanandam et al., 2001), genome-wide association studies (GWAS) were designed to survey the role of common genetic variations in complex human diseases. It was expected that GWAS would have the advantage of not relying on prior knowledge of biological pathways compared with “candidate gene” studies (Tabor et al., 2002; Wang et al., 2005), because it assays a dense set of single-nucleotide polymorphisms (SNPs) across the whole genome. This advantage allows GWAS to overcome the bias of “candidate gene” studies due to incomplete prior knowledge. It was also expected that GWAS would have higher power and finer resolution to identify genetic variants of modest effects compared to family-based linkage studies (Risch & Merikangas, 1996).
The success of identifying genes for age-related macular degeneration (AMD) under the GWAS paradigm (Klein et al., 2005) convinced the genetics community on the efficiency and feasibility of the GWAS approach to identify unknown disease-associated variants. This study used a commercial genotyping array and assayed about 100,000 SNPs throughout the human genome. It identified the association of complement factor H (CFH) with AMD. The success of finding a common risk allele with an odds ratio (OR) of 4.6 in a small sample set of 96 cases and 50 controls has generated considerable excitement in the genetics community. The p-value of the strongest SNP association surpassed the genome-wide significance threshold after the Bonferroni correction. More importantly, this finding was replicated in the following-up studies (Donoso et al., 2010). Undoubtedly, this encouraging finding raised the confidence among researchers to detect genetic variants that underlie various complex diseases through GWAS. In 2007, the Wellcome Trust Case Control Consortium (WTCCC) published the results of seven GWAS, including Bipolar Disorder, Coronary Artery Disease, Crohn's Disease, Hypertension, Rheumatoid Arthritis, Type 1 Diabetes, and Type 2 Diabetes (The Wellcome Trust Case Control Consortium, 2007). The WTCCC study is considered the starting point of large-scale GWAS (Visscher et al., 2012). Since then, an increasing number of GWAS have been conducted and over 10,000 loci have been reported to be significantly associated with at least one complex trait (see the web resource of GWAS catalog (Hindorff et al., 2009), http://www.genome.gov/gwastudies/).
14 - eQTL mapping
- from Part III - Single nucleotide polymorphisms, copy number variants, haplotypes and eQTLs
-
- By Mengjie Chen, Yale University, Can Yang, Hong Kong Baptist University, Cong Li, Yale University, Hongyu Zhao, Yale University
- Edited by Krishnarao Appasani
- Foreword by Stephen W. Scherer, Peter M. Visscher
-
- Book:
- Genome-Wide Association Studies
- Published online:
- 18 December 2015
- Print publication:
- 14 January 2016, pp 208-228
-
- Chapter
- Export citation
-
Summary
Introduction
With an influx of successful genome-wide association studies to identify genetic variations associated with complex diseases, an unprecedented wealth of knowledge has been accumulated for SNP–phenotype associations (McCarthy et al., 2008; Witte 2010; Manolio 2013). However, many SNP–disease associations do not lend themselves to molecular interpretations, because many of the identified loci are located outside of the coding regions. Even when a gene can be inferred to be causal, there is often a significant gap towards the understanding of the underlying molecular mechanisms (Schadt et al., 2005; McCarthy et al., 2008). Genome-wide eQTL mapping has been one effective approach to bridge this gap (Mackay et al., 2009). In eQTL studies, gene expression levels measured by high-throughput technologies, such as microarrays and RNA-Seq, are treated as quantitative traits. Marker genotypes are also collected from the same set of individuals, and statistical analyses are performed to detect associations between markers and expression traits. By simultaneously capturing many regulatory interactions, eQTLs offer valuable insights on the genetic architecture of expression regulation (Rockman and Kruglyak 2006). The ultimate goal of eQTL studies is to elucidate how genetic variations affect phenotypes by using gene expression levels as intermediate molecular phenotypes (Nica and Dermitzakis 2008). In this chapter, we provide an overview of the eQTL analysis workflow (Figure 14.1), introduce publicly available tools for analysis, and further discuss challenges and issues.
Data pre-processing
Genome-wide eQTL mapping considers high-density SNP genotype data and gene expression data from the same individuals in a segregating population. Both require appropriate pre-processing as described below for subsequent analysis.
Genotype data
Three quality control (QC) criteria are often used in the pre-processing of the genotype data. (1) Missing rate: individuals with a large proportion of missing SNP genotypes (e.g., 10%) should be excluded because the DNA samples of those individuals may be of poor quality. SNPs with a large missing rate (e.g., 5%) should also be filtered out. (2) Hardy–Weinberg Equilibrium (HWE): statistically significant deviations from HWE often result from genotyping errors. Therefore, SNPs that fail an exact HWE test (e.g., a P-value less than 0.001) should be filtered out. The criterion does not apply to haploid organisms, such as yeast. (3) Minor allele frequency (MAF): SNPs with low MAF (e.g., 0.05) are sometimes filtered out because of the insufficient statistical power for studies with a relatively small sample size and potentially higher genotype calling error.