Publications by authors named "Xiaoyan Ge"

36 Publications

Metrological properties of neuropsychological tests for measuring cognitive change in individuals with prodromal Alzheimer's disease.

Aging Ment Health 2021 Aug 19:1-9. Epub 2021 Aug 19.

Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, China.

Objectives: In Alzheimer's Disease (AD) research, choosing appropriate method for measuring change in cognitive function over time can be challenging. The aim for this study was to examine the sensitivity of four neuropsychological tests used to measure cognition during the transition from mild cognitive impairment (MCI) to AD, and the impacts of associated covariates.

Methods: We enrolled 223 patients with MCI who progressed to AD and had completed multiple follow-up assessments in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We constructed nonlinear mixed model for multivariate longitudinal data assuming that multiple neuropsychological tests would exhibit nonlinear transformation of a common factor in the latent cognitive process underlying the progression from MCI to AD.

Results: The Clinical Dementia Rating-Sum of the Boxes (CDR-SB) and Alzheimer's Disease Assessment Scale (11 items; ADAS-11) were more sensitive to cognitive changes in individuals with higher cognitive function, the Functional Activities Questionnaire (FAQ) was more sensitive to cognitive changes in individuals with middle cognitive function, and the Mini-Mental State Examination (MMSE) was more sensitive to cognitive changes in individuals with lower cognitive function. Gender ( = 0.0139) and educational level ( = 0.0094) had varying effects on different tests, such that men performed better on the FAQ and CDR-SB, and individuals with higher educational level tended to perform better on the FAQ and MMSE.

Conclusions: When choosing appropriate neuropsychological tests in cognitive measurements, the cognitive functional level of the patient as well as the impacts of covariates should be considered.
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http://dx.doi.org/10.1080/13607863.2021.1966746DOI Listing
August 2021

Activities of daily living as a longitudinal moderator of the effect of autonomic dysfunction on anxiety and depression of Parkinson's patients.

Brain Behav 2021 08 1;11(8):e2297. Epub 2021 Aug 1.

Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, China.

Background: There is no clear time point for the onset of depression and anxiety in Parkinson's disease (PD), and their atypical physical symptoms often overlap with other nonmotor symptoms. Autonomic dysfunction usually appears earlier than motor symptoms, seriously impairing activities of daily living (ADL), even quality of life. Whether autonomic dysfunction can affect depression and anxiety in PD patients through ADL is still unclear.

Methods: We conducted three progressive autoregressive mediation models to evaluate whether ADL may mediate the association between autonomic symptom burden, where the mediation chain with autonomic function as an independent variable, ADL as a mediating variable, and anxiety and depression as dependent variables. The ADL of PD patients were measured by the Scales for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT) and Modified Schwab and England ADL scale, respectively, and the status of depression and anxiety were measured by the Geriatric Depression Scale (GDS) and State-Trait Anxiety Inventory (STAI).

Results: There were 338 PD patients, including 220 males and 118 females. Demographic information, including age, gender, and education level, were not correlated with the depression and anxiety. Model III had the smallest AIC (AIC = 12,669.89), and the cross-lagged relations were not statistically significant, so we selected Model II as the optimal model. In Model II, longitudinal autoregressive mediated effect and longitudinal mediated effect of autonomic dysfunction affecting anxiety and depression through ADL were not statistically significant, suggesting longitudinal changes of autonomic dysfunction were independent of anxiety and depression through ADL. Contemporaneous mediated effects of autonomic dysfunction affecting anxiety and depression through ADL were statistically significant, suggesting contemporaneous autonomic dysfunction may contribute to anxiety and depression through ADL.

Conclusions: Targeted prevention and intervention measures for autonomic dysfunction and ADL should be taken to preserve and improve self-perceived life satisfaction in the clinical practice and preventive health care of PD.
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http://dx.doi.org/10.1002/brb3.2297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413789PMC
August 2021

Risk Assessment During Longitudinal Progression of Cognition in Older Adults: A Community-based Bayesian Networks Model.

Curr Alzheimer Res 2021 ;18(3):232-242

Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, China.

Background: Cognitive dysfunction, particularly in Alzheimer's disease (AD), seriously affects the health and quality of life of older adults. Early detection can prevent and slow cognitive decline.

Objective: This study aimed at evaluating the role of socio-demographic variables, lifestyle, and physical characteristics in cognitive decline during AD progression and analyzing the probable causes and predicting stages of the disease.

Methods: By analyzing data of 301 subjects comprising normal elderly and patients with mild cognitive impairment (MCI) or AD from six communities in Taiyuan, China, we identified the influencing factors during AD progression by a Logistic Regression model (LR) and then assessed the associations between variables and cognition using a Bayesian Networks (BNs) model.

Results: The LR revealed that age, sex, family status, education, income, character, depression, hypertension, disease history, physical exercise, reading, drinking, and job status were significantly associated with cognitive decline. The BNs model revealed that hypertension, education, job status, and depression affected cognitive status directly, while character, exercise, sex, reading, income, and family status had intermediate effects. Furthermore, we predicted probable cognitive stages of AD and analyzed probable causes of these stages using a model of causal and diagnostic reasoning.

Conclusion: The BNs model lays the foundation for causal analysis and causal inference of cognitive dysfunction, and the prediction model of cognition in older adults may help the development of strategies to control modifiable risk factors for early intervention in AD.
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http://dx.doi.org/10.2174/1567205018666210608110329DOI Listing
January 2021

Evaluation of lightwand-guided endotracheal intubation for patients with missing or no teeth: a randomized controlled study.

Braz J Anesthesiol 2021 Jul-Aug;71(4):395-401. Epub 2021 Apr 8.

Anhui Medical University, The First Affiliated Hospital, Department of Anesthesiology, Hefei, China. Electronic address:

Background: Unhealthy teeth can seriously affect general health and increase the risk of death in elderly people. There has been no confirmation of which device is most effective for elderly patients with teeth loss. Therefore, we compared four intubation devices in elderly patients with partial and total tooth loss aiming to reduce risk during anesthesia.

Methods: Two hundred patients were randomized to undergo tracheal intubation with the Macintosh laryngoscope, the Glidescope, the Fiberoptic bronchoscope or the Lightwand as part of general anesthesia. A unified protocol of anesthetic medications was used. HR and BP were measured at T, T, T, T, T and T. Catecholamine (epinephrine and norepinephrine) blood samples were drawn at T, T and T. Intubation time and postoperative complications, including dental damage and losses, were recorded.

Results: Reduced fluctuations in HR, DBP, and SBP were observed in the Lightwand group. Intubation time was significantly shorter in the Lightwand group (p < 0.05). There was no statistically significant difference between the groups in epinephrine levels, but norepinephrine levels were less volatile in the Fiberoptic bronchoscope and Lightwand groups. Fewer patients in the Lightwand group experienced dental damage and other postoperative complications than in the other three groups. Although a higher success rate on the first attempt was as high as in the Fiberoptic bronchoscope group, shorter intubation time was observed only in the Lightwand group.

Conclusion: The Lightwand offers less hemodynamic stimulation than the Macintosh laryngoscope, Glidescope, and Fiberoptic bronchoscope. Because it had the shortest intubation time, the Lightwand caused the least damage to the teeth and throat of elderly patients. Our findings showed that tracheal intubation with the Lightwand was advantageous for preventing cardiovascular stress responses with short intubation times and fewer postoperative complications.
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http://dx.doi.org/10.1016/j.bjane.2021.03.002DOI Listing
April 2021

The path linking disease severity and cognitive function with quality of life in Parkinson's disease: the mediating effect of activities of daily living and depression.

Health Qual Life Outcomes 2021 Mar 17;19(1):92. Epub 2021 Mar 17.

Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Department of Health Statistics, School of Public Health, Shanxi Medical University, 56 South XinJian Road, Taiyuan, 030001, People's Republic of China.

Background: Research on quality of life (QOL) with Parkinson's disease (PD) has examined direct influencing factors, not mediators. The study aim was to explore whether PD severity and poor cognitive function may decrease physical and mental QOL by reducing activities of daily living (ADL) and increasing depression in sequence.

Methods: We conducted a cross-sectional questionnaire study of 150 PD hospital patients in China. PD severity, cognitive function, ADL, depression, and QOL were evaluated. We used structural equation modeling to analyze the mediating effects of ADL and depression on the association between PD severity/cognition and the physical health and mental health component summary scores measured by the SF36 quality of life instrument.

Results: There was a significant mediating effect of PD severity on physical health via ADL and depression (95% CI: - 0.669, - 0.026), and a significant direct effect (p < 0.001). The mediating effect of PD severity on mental health via ADL and depression was significant (95% CI: - 2.135, - 0.726), but there was no direct effect (p = 0.548). There was a significant mediating effect of cognitive function on physical health via ADL and depression (95% CI: 0.025, 0.219) and a significant direct effect (p < 0.001). The mediating effect of cognitive function on mental health via ADL and depression was significant (95% CI: 0.256, 0.645), but there was no direct effect (p = 0.313). The physical health models showed a partial mediation, and the mental health models showed a complete mediation, of ADL and depression.

Conclusions: PD severity and cognitive function increase depression by reducing ADL, leading to lower QOL, and directly or indirectly affect physical health and mental health through different pathways.
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http://dx.doi.org/10.1186/s12955-021-01740-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972188PMC
March 2021

Identification of vascular dementia and Alzheimer's disease hub genes expressed in the frontal lobe and temporal cortex by weighted co-expression network analysis and construction of a protein-protein interaction.

Int J Neurosci 2021 Jan 18:1-12. Epub 2021 Jan 18.

Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, P.R. China.

It is difficult to distinguish cognitive decline due to AD from that sustained by cerebrovascular disease in view of the great overlap. It is uncertain in the molecular biological pathway behind AD and VaD. Our study aimed to explore the hub molecules and their associations with each other to identify potential biomarkers and therapeutic targets for the AD and VaD.Methods: We screened the differentially expressed genes of AD and VaD, used weighted gene co-expression network analysis and then constructed a VaD-AD-specific protein-protein interaction network with functional annotation to their related metabolic pathways. Finally, we performed a ROC curve analysis of hub proteins to get an idea about their diagnostic value. In the frontal lobe and temporal cortex, hub genes were identified. With regard to VaD, there were only three hub genes which encoded the neuropeptides, and The AUC of these genes were 0.804, 0.768 and 0.779, respectively. One signature was established for these three hub genes with AUC of 0.990. For the identification of AD and VaD, all hub genes were receptors. These genes included and . The AUC of these genes were 0.853, 0.859, 0.796, 0.775, 0.706, 0.677, 0.696, 0.668 and 0.652, respectively. The other signature was built for eleven hub genes with AUC of 0.990. In the frontal lobe and temporal cortex regions, hub genes are used as diagnostic markers, which may provide insight into personalized potential biomarkers and therapeutic targets for patients with VaD and AD.
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http://dx.doi.org/10.1080/00207454.2020.1860966DOI Listing
January 2021

Predicting Alzheimer's disease based on survival data and longitudinally measured performance on cognitive and functional scales.

Psychiatry Res 2020 09 8;291:113201. Epub 2020 Jun 8.

Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, China; Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment. Electronic address:

This study assessed how well longitudinally taken cognitive and functional scales from people with mild cognitive impairment (MCI) predict conversion to Alzheimer's disease (AD). Participants were individuals with baseline MCI from the Alzheimer's Disease Neuroimaging Initiative. Scales included the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) 11 and 13, the Mini Mental State Examination (MMSE), and the Functional Assessment Questionnaire (FAQ). A joint modelling approach compared performance on the four scales for dynamic prediction of risk for AD. The goodness of fit measures included log likelihood, the Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC). The area under the curve (AUC) of the receiver operating characteristic assessed predictive accuracy. The parameter α in the ADAS-Cog11, ADAS-Cog13, MMSE, and FAQ joint models was statistically significant. Joint MMSE and FAQ models had better goodness of fit. FAQ had the best predictive accuracy. Cognitive and functional impairment assessment scales are strong screening predictors when repeated measures are available. They could be useful for predicting risk for AD in primary healthcare.
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http://dx.doi.org/10.1016/j.psychres.2020.113201DOI Listing
September 2020

Chlorella vulgaris on the cathode promoted the performance of sediment microbial fuel cells for electrogenesis and pollutant removal.

Sci Total Environ 2020 Aug 17;728:138011. Epub 2020 Mar 17.

State Environmental Protection Engineering Center for Pollution Treatment and Control in Textile Industry, College of Environmental Science and Engineering, Donghua University, Shanghai 201620, PR China.

The lack of electron acceptors in cathode has limited the widespread application of sediment microbial fuel cells (SMFCs). In this study, Chlorella vulgaris (C. vulgaris) was added to the cathode to produce oxygen as an electron acceptor. The synergistic effects between C. vulgaris and electrogenic microorganisms in SMFCs were investigated, and were shown to enhance biodegradation of organic matter in sediments and convert chemical energy into electrical energy. Results showed that the addition of C. vulgaris on the cathode of SMFCs significantly reduced their internal resistance. The low algae concentration SMFC group reduced the initial internal resistance by 67.4% under illumination and produced a maximum power density of 5.17 W/m, which was 6 times higher than that of SMFCs without addition of C. vulgaris. We also obtained organic matter removal efficiencies 37.2% higher after 16 days, which accelerated the startup time for three times. It was demonstrated that IEF-N and OP, respectively, were forms of nitrogen and phosphorus removed by SMFCs. Additionally, high-throughput sequencing of microbial communities indicated that C. vulgaris increased the abundance of electrogenic bacteria (Geobacter and Desulfobulbaceae) in the anode and types of photosynthetic bacteria that support oxygen production in the cathode. The combined application of microalgae- and SMFC-based technologies offer a promising remediation approach for organically-contaminated sediments.
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http://dx.doi.org/10.1016/j.scitotenv.2020.138011DOI Listing
August 2020

Untangling the nitrate removal pathways for a constructed wetland- sponge iron coupled system and the impacts of sponge iron on a wetland ecosystem.

J Hazard Mater 2020 07 25;393:122407. Epub 2020 Feb 25.

College of Environmental Science and Engineering, State Environmental Protection Engineering Center for Pollution Treatment and Control in Textile Industry, Donghua University, Shanghai, 201620, China.

Sponge iron (s-Fe) is a potential alternative electron donor for nitrate reduction. To gain insight into the mechanism of denitrification in a constructed wetland- sponge iron coupled system (CW-Fe system), the removal performance and reduction characteristics of nitrate in constructed wetlands (CWs) with and without s-Fe application were compared. Results indicated that s-Fe intensified the removal of nitrate with a 6h-HRT. The nitrate removal efficiency was improved by 16-76 % with various influent NO-N concentrations (10-30 mg L) and at a chemical oxygen demand(COD)/N ratio of 5. The rates of chemical denitrification were positively correlated with the dosage of s-Fe and negatively correlated with the influent COD concentration. 16S rDNA sequencing revealed that hydrogen-utilizing autotrophic denitrifier of Hydrogenophaga was highly enriched (accounting for 10 % of the total OTUs) only in CW-Fe system. The micro-environment created by s-Fe was suitable for heterotrophic denitrifiers of Thauera, Tessaracoccus and Simplicispira. The determination of physiological indicators for plants showed that the application of s-Fe causes abiotic stress to wetland plants (Canna indica L.). Nevertheless, s-Fe can be used as a substrate for CWs, since it allows a high-efficiency removal of nitrate by mediating chemical denitrification and hydrogen-driven autotrophic denitrification.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122407DOI Listing
July 2020

Notochord vacuoles absorb compressive bone growth during zebrafish spine formation.

Elife 2020 01 29;9. Epub 2020 Jan 29.

Department of Cell Biology, Duke University, Durham, United States.

The vertebral column or spine assembles around the notochord rod which contains a core made of large vacuolated cells. Each vacuolated cell possesses a single fluid-filled vacuole, and loss or fragmentation of these vacuoles in zebrafish leads to spine kinking. Here, we identified a mutation in the kinase gene that causes fragmentation of notochord vacuoles and a severe congenital scoliosis-like phenotype in zebrafish. Live imaging revealed that Dstyk regulates fusion of membranes with the vacuole. We find that localized disruption of notochord vacuoles causes vertebral malformation and curving of the spine axis at those sites. Accordingly, in mutants the spine curves increasingly over time as vertebral bone formation compresses the notochord asymmetrically, causing vertebral malformations and kinking of the axis. Together, our data show that notochord vacuoles function as a hydrostatic scaffold that guides symmetrical growth of vertebrae and spine formation.
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http://dx.doi.org/10.7554/eLife.51221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012607PMC
January 2020

Effect of n-3 long-chain polyunsaturated fatty acids on mild cognitive impairment: a meta-analysis of randomized clinical trials.

Eur J Clin Nutr 2020 04 5;74(4):548-554. Epub 2019 Dec 5.

Department of Health Statistics, School of Public Health, Shanxi Provincial Key Laboratory of Major Disease Risk Assessment, Shanxi Medical University, 56 South XinJian Road, Taiyuan, 030001, China.

N-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have positive effect on cognitive function with mild cognitive impairment (MCI) is still controversial. The aim for this meta-analysis was to assess the scientific evidence published in the last 10 years on the effects of n-3 LC-PUFAs intake on MCI patients to explore whether n-3 LC-PUFAs have positive effective. A comprehensive literature search was developed using the Google Scholar, EMBASE, and PubMed database. The pooled effect for all studies was calculated using random-effects model. And the terms of weighted mean difference (WMD) with 95% confidence interval (CI) was pooled and indicated the effects. Heterogeneity was assessed by I statistics. A total of seven randomized clinical trials involving 213 cases of intervention and 221 cases of placebo were included in this analysis. Compared with placebo, n-3 LC-PUFAs supplements effectively improved cognition in elders with MCI (WMD = 0.85, 95% CI: 0.04-1.67, Z = 2.05, P = 0.04). Slight heterogeneity was detected across studies. Our results provided further evidence that n-3 LC-PUFAs may have beneficial effect in elderly with MCI.
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http://dx.doi.org/10.1038/s41430-019-0544-4DOI Listing
April 2020

Bioenergy generation and simultaneous nitrate and phosphorus removal in a pyrite-based constructed wetland-microbial fuel cell.

Bioresour Technol 2020 Jan 30;296:122350. Epub 2019 Oct 30.

College of Environmental Science and Engineering, State Environmental Protection Engineering Center for Pollution Treatment and Control in Textile Industry, Donghua University, Shanghai 201620, China.

This study investigates the performance of a pyrite-based constructed wetland-microbial fuel cell (PCW-MFC) in chemical oxygen demand (COD), nitrate (NO-N), total inorganic nitrogen (TIN), and total phosphorus (TP) removal and bioelectricity generation, and explores the mechanisms involved. Four microcosms were used: a constructed wetland (CW), a pyrite-based constructed wetland (PCW), a constructed wetland-microbial fuel cell (CW-MFC), and a PCW-MFC. After 180 days' operation, the PCW-MFC exhibited enhanced simultaneous nitrate and phosphorus removal and bioelectricity output. The maximum COD, NO-N, TIN, and TP removal efficiencies in the PCW-MFC were 71.9%, 70.1%, 63.2%, and 91.2%, respectively, for a hydraulic retention time (HRT) of 6 h. The mean bioelectricity output of the PCW-MFC was 19.0-28.4% higher than that of the CW-MFC. The nitrate removal rate constant of the PCW-MFC was 1.04 d, which is significantly higher than those of the others. Geobacter and sulfate-reducing bacteria were enriched in the PCW-MFC.
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http://dx.doi.org/10.1016/j.biortech.2019.122350DOI Listing
January 2020

Micro-aeration with hollow fiber membrane enhanced the nitrogen removal in constructed wetlands.

Environ Sci Pollut Res Int 2020 Jul 5;27(21):25877-25885. Epub 2019 Oct 5.

State Environmental Protection Engineering Center for Pollution Treatment and Control in Textile Industry, College of Environmental Science and Engineering, Donghua University, Shanghai, 201620, People's Republic of China.

The nitrogen removal efficiency in constructed wetlands (CWs) was largely affected by the dissolved oxygen (DO). In this study, micro-aeration with different numbers of hollow fiber membrane modules (HFMEs) was adopted to increase the oxygen availability and improve the nitrogen removal efficiency in CWs under different air temperatures and different hydraulic retention time (HRT). Compared to the plant oxygen release (ROL) of wetland plants and traditional mechanical aeration, HFME increased the oxygen availability and enhanced the nitrogen removal efficiency in CWs. The COD and NH-N removal efficiencies increased with the increase of the HMFE. TN removal efficiency was increased by 8~16% after the application of HFME in CWs in the high-temperature stage. However, less HFME in CW-M1 realized the highest TN removal efficiency in low- and medium-temperature stages. At low temperature after 4-day HRT, the DO concentration respectively reached 6.25 mg L and 3.25 mg L in the upper zone and the bottom of CW-M1. The TN removal efficiencies in the upper zone of CW-M1 (60.69%) and the bottom of CW-M1 (64.98%) were all significantly higher than those in the upper zone of CK (35.98%) and the bottom of CK (39.9%). In addition, the microbial biomass and community analyses revealed that CW-M1 showed the most nitrifying bacteria and the best metabolic activity of bacteria. HEMF in CW-M1 also increased the nitrifying capacity from 0.12 to 0.46 mg kg h. The application of HFME in CWs accelerated the nitrification process by enhancing nitrifying bacteria and less HFME realized the highest TN removal efficiency through nitrification-denitrification processes. Graphical abstract The application of hollow fiber membrane modules in CWs enhanced the pollutants (TN and COD) removal efficiency in the process of biological nitrification-denitrification and increased the number of nitrifying bacteria.
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http://dx.doi.org/10.1007/s11356-019-06315-3DOI Listing
July 2020

Aberrant Function of the C-Terminal Tail of HIST1H1E Accelerates Cellular Senescence and Causes Premature Aging.

Am J Hum Genet 2019 09 22;105(3):493-508. Epub 2019 Aug 22.

Department of Psychiatry, University of Pretoria, Weskoppies Hospital, Pretoria, 0001 South Africa.

Histones mediate dynamic packaging of nuclear DNA in chromatin, a process that is precisely controlled to guarantee efficient compaction of the genome and proper chromosomal segregation during cell division and to accomplish DNA replication, transcription, and repair. Due to the important structural and regulatory roles played by histones, it is not surprising that histone functional dysregulation or aberrant levels of histones can have severe consequences for multiple cellular processes and ultimately might affect development or contribute to cell transformation. Recently, germline frameshift mutations involving the C-terminal tail of HIST1H1E, which is a widely expressed member of the linker histone family and facilitates higher-order chromatin folding, have been causally linked to an as-yet poorly defined syndrome that includes intellectual disability. We report that these mutations result in stable proteins that reside in the nucleus, bind to chromatin, disrupt proper compaction of DNA, and are associated with a specific methylation pattern. Cells expressing these mutant proteins have a dramatically reduced proliferation rate and competence, hardly enter into the S phase, and undergo accelerated senescence. Remarkably, clinical assessment of a relatively large cohort of subjects sharing these mutations revealed a premature aging phenotype as a previously unrecognized feature of the disorder. Our findings identify a direct link between aberrant chromatin remodeling, cellular senescence, and accelerated aging.
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http://dx.doi.org/10.1016/j.ajhg.2019.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731364PMC
September 2019

Risk classification for conversion from mild cognitive impairment to Alzheimer's disease in primary care.

Psychiatry Res 2019 08 16;278:19-26. Epub 2019 May 16.

Department of Health Statistics, School of Public Health, Shanxi Medical University, 56 Xinjiannanlu Street, Taiyuan, China; Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment. Electronic address:

There is a pressing need to identify individuals at high risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) based on available repeated cognitive measures in primary care. Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we applied a joint latent class mixed model (JLCM) to derive a 3-class solution: low risk (72.65%), medium risk (20.41%) and high risk (6.94%). In the low-risk group, individuals with lower daily activity and ApoEε4 carriers were at greater risk of conversion from MCI to AD. In the medium-risk group, being female, single, and an ApoEε4 carrier increased risk of conversion to AD. In the high-risk group, individuals with lower education level and single individuals were at greater risk of conversion to AD. Individual dynamic prediction for conversion from MCI to AD after 10 years was derived. Accurate identification of conversion from MCI to AD contributes to earlier close monitoring, appropriate management, and targeted interventions. Thereby, it can reduce avoidable hospitalizations for the high-risk MCI population. Moreover, it can avoid expensive follow-up tests that may provoke unnecessary anxiety for low-risk individuals and their families.
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http://dx.doi.org/10.1016/j.psychres.2019.05.027DOI Listing
August 2019

Publisher Correction: Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA.

Nat Med 2019 Apr;25(4):701-702

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

In the version of this article originally published, some cases that were presented in Fig. 3 should have been underlined but were not. The appropriate cases have now been underlined. The error has been corrected in the print, PDF and HTML versions of the article.
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http://dx.doi.org/10.1038/s41591-019-0391-9DOI Listing
April 2019

Preparation and characterization of edible starch film reinforced by laver.

Int J Biol Macromol 2019 May 8;129:944-951. Epub 2019 Feb 8.

Collage of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China.

Edible starch film reinforced by laver was developed and characterized. The relationship between processing technologies, microstructures and performances was established. When the laver was added into cold starch suspension, the laver flack (fiber) simply act as reinforcing agent to improve the mechanical properties of the starch matrix, which results in increasing modulus and tensile strength. When the laver was added into hot starch suspension and mixed under shear stress, the protein containing in laver will release out and mix with starch, which results in a starch-protein-laver fiber hybrid composites. In the hybrids system, fiber improves the mechanical properties of the starch-based film about 25%, while the protein reduces the moisture sensitivity and gas permeability about 45%. Scanning electron microscopic observation indicated good compatibility between starch matrix and laver. The cellulose containing in laver kept its semi-crystalline structure after processing, which was used to explain the reinforcing mechanism. Some chemical bounds between starch and protein containing in laver was detected by FTIR. Since all the components used in this work are from food sources, the prepared films are safe for food packaging and application as edible films.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.02.045DOI Listing
May 2019

Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA.

Nat Med 2019 03 28;25(3):439-447. Epub 2019 Jan 28.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Current non-invasive prenatal screening is targeted toward the detection of chromosomal abnormalities in the fetus. However, screening for many dominant monogenic disorders associated with de novo mutations is not available, despite their relatively high incidence. Here we report on the development and validation of, and early clinical experience with, a new approach for non-invasive prenatal sequencing for a panel of causative genes for frequent dominant monogenic diseases. Cell-free DNA (cfDNA) extracted from maternal plasma was barcoded, enriched, and then analyzed by next-generation sequencing (NGS) for targeted regions. Low-level fetal variants were identified by a statistical analysis adjusted for NGS read count and fetal fraction. Pathogenic or likely pathogenic variants were confirmed by a secondary amplicon-based test on cfDNA. Clinical tests were performed on 422 pregnancies with or without abnormal ultrasound findings or family history. Follow-up studies on cases with available outcome results confirmed 20 true-positive, 127 true-negative, zero false-positive, and zero-false negative results. The initial clinical study demonstrated that this non-invasive test can provide valuable molecular information for the detection of a wide spectrum of dominant monogenic diseases, complementing current screening for aneuploidies or carrier screening for recessive disorders.
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http://dx.doi.org/10.1038/s41591-018-0334-xDOI Listing
March 2019

Developing acrylated epoxidized soybean oil coating for improving moisture sensitivity and permeability of starch-based film.

Int J Biol Macromol 2019 Mar 30;125:370-375. Epub 2018 Nov 30.

Centre for Polymers from Renewable Resources, SFSE, South China University of Technology, Guangzhou 510640, China.

Acrylated epoxidized soybean oil (AESO)-based coatings were developed to reduce moisture sensitivity and permeability of starch-based materials. The coating was applied on starch based films by dipping the samples on AESO-based coating solutions, followed by crosslinking with ultraviolet (UV) light. Effect of AESO concentration, photoinitiator content and processing conditions on the performance of coated starch-based film was systematically investigated, in particular the effect of coating on moisture absorption, permeability and mechanical properties. The modified surface was characterized by scanning electronic microscopy and Fourier transform infrared spectroscopy. The results showed that the moisture sensitivity of the starch-based sheets was reduced significantly since the crosslinked AESO acted as a hydrophobic layer. Moisture permeability was decreased more than 10 times after AESO treatment. It was found that the crosslinking density acted as one of the key factors, so even a very thin layer of AESO could achieve good water resistance.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.11.239DOI Listing
March 2019

Genotype-phenotype correlations in individuals with pathogenic RERE variants.

Hum Mutat 2018 05 25;39(5):666-675. Epub 2018 Jan 25.

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas.

Heterozygous variants in the arginine-glutamic acid dipeptide repeats gene (RERE) have been shown to cause neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH). Here, we report nine individuals with NEDBEH who carry partial deletions or deleterious sequence variants in RERE. These variants were found to be de novo in all cases in which parental samples were available. An analysis of data from individuals with NEDBEH suggests that point mutations affecting the Atrophin-1 domain of RERE are associated with an increased risk of structural eye defects, congenital heart defects, renal anomalies, and sensorineural hearing loss when compared with loss-of-function variants that are likely to lead to haploinsufficiency. A high percentage of RERE pathogenic variants affect a histidine-rich region in the Atrophin-1 domain. We have also identified a recurrent two-amino-acid duplication in this region that is associated with the development of a CHARGE syndrome-like phenotype. We conclude that mutations affecting RERE result in a spectrum of clinical phenotypes. Genotype-phenotype correlations exist and can be used to guide medical decision making. Consideration should also be given to screening for RERE variants in individuals who fulfill diagnostic criteria for CHARGE syndrome but do not carry pathogenic variants in CHD7.
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http://dx.doi.org/10.1002/humu.23400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903952PMC
May 2018

Use of Exome Sequencing for Infants in Intensive Care Units: Ascertainment of Severe Single-Gene Disorders and Effect on Medical Management.

JAMA Pediatr 2017 12 4;171(12):e173438. Epub 2017 Dec 4.

Department of Pediatrics, Genetics Division, University of Tennessee Health Science Center, Memphis.

Importance: While congenital malformations and genetic diseases are a leading cause of early infant death, to our knowledge, the contribution of single-gene disorders in this group is undetermined.

Objective: To determine the diagnostic yield and use of clinical exome sequencing in critically ill infants.

Design, Setting, And Participants: Clinical exome sequencing was performed for 278 unrelated infants within the first 100 days of life who were admitted to Texas Children's Hospital in Houston, Texas, during a 5-year period between December 2011 and January 2017. Exome sequencing types included proband exome, trio exome, and critical trio exome, a rapid genomic assay for seriously ill infants.

Main Outcomes And Measures: Indications for testing, diagnostic yield of clinical exome sequencing, turnaround time, molecular findings, patient age at diagnosis, and effect on medical management among a group of critically ill infants who were suspected to have genetic disorders.

Results: The mean (SEM) age for infants participating in the study was 28.5 (1.7) days; of these, the mean (SEM) age was 29.0 (2.2) days for infants undergoing proband exome sequencing, 31.5 (3.9) days for trio exome, and 22.7 (3.9) days for critical trio exome. Clinical indications for exome sequencing included a range of medical concerns. Overall, a molecular diagnosis was achieved in 102 infants (36.7%) by clinical exome sequencing, with relatively low yield for cardiovascular abnormalities. The diagnosis affected medical management for 53 infants (52.0%) and had a substantial effect on informed redirection of care, initiation of new subspecialist care, medication/dietary modifications, and furthering life-saving procedures in select patients. Critical trio exome sequencing revealed a molecular diagnosis in 32 of 63 infants (50.8%) at a mean (SEM) of 33.1 (5.6) days of life with a mean (SEM) turnaround time of 13.0 (0.4) days. Clinical care was altered by the diagnosis in 23 of 32 patients (71.9%). The diagnostic yield, patient age at diagnosis, and medical effect in the group that underwent critical trio exome sequencing were significantly different compared with the group who underwent regular exome testing. For deceased infants (n = 81), genetic disorders were molecularly diagnosed in 39 (48.1%) by exome sequencing, with implications for recurrence risk counseling.

Conclusions And Relevance: Exome sequencing is a powerful tool for the diagnostic evaluation of critically ill infants with suspected monogenic disorders in the neonatal and pediatric intensive care units and its use has a notable effect on clinical decision making.
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http://dx.doi.org/10.1001/jamapediatrics.2017.3438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359927PMC
December 2017

The next generation of population-based spinal muscular atrophy carrier screening: comprehensive pan-ethnic SMN1 copy-number and sequence variant analysis by massively parallel sequencing.

Genet Med 2017 08 26;19(8):936-944. Epub 2017 Jan 26.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

Purpose: To investigate pan-ethnic SMN1 copy-number and sequence variation by hybridization-based target enrichment coupled with massively parallel sequencing or next-generation sequencing (NGS).

Methods: NGS reads aligned to SMN1 and SMN2 exon 7 were quantified to determine the total combined copy number of SMN1 and SMN2. The ratio of SMN1 to SMN2 was calculated based on a single-nucleotide difference that distinguishes the two genes. SMN1 copy-number results were compared between the NGS and quantitative polymerase chain reaction and/or multiplex ligation-dependent probe amplification. The NGS data set was also queried for the g.27134T>G single-nucleotide polymorphism (SNP) and other SMN1 sequence pathogenic variants.

Results: The sensitivity of the test to detect spinal muscular atrophy (SMA) carriers with one copy of SMN1 was 100% (95% confidence interval (CI): 95.9-100%; n = 90) and specificity was 99.6% (95% CI: 99.4-99.7%; n = 6,648). Detection of the g.27134T>G SNP by NGS was 100% concordant with an restriction fragment-length polymorphism method (n = 493). Ten single-nucleotide variants in SMN1 were detectable by NGS and confirmed by gene-specific amplicon-based sequencing. This comprehensive approach yielded SMA carrier detection rates of 90.3-95.0% in five ethnic groups studied.

Conclusion: We have developed a novel, comprehensive SMN1 copy-number and sequence variant analysis method by NGS that demonstrated improved SMA carrier detection rates across the entire population examined.Genet Med advance online publication 19 January 2017.
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http://dx.doi.org/10.1038/gim.2016.215DOI Listing
August 2017

Effects of lignin and surfactant on adsorption and hydrolysis of cellulases on cellulose.

Biotechnol Biofuels 2016 26;9:20. Epub 2016 Jan 26.

College of Forestry, Northwest A and F University, 3 Taicheng Road, Yangling, 712100 China.

Background: Considerable works have been reported concerning the obstruction of enzymatic hydrolysis efficiency by lignin. However, there is a lack of information about the influence of lignin on the adsorption of cellulases on cellulose, along with the hydrolytic activity of the cellulases adsorbed on lignin. In addition, limited discovery has been reported about the influence of additives on cellulase desorption from lignin and lignocellulosic materials. In this work, the effects of lignin on cellulase adsorption and hydrolysis of Avicel were investigated and the effects of Tween 80 on cellulases adsorption and desorption on/from lignin and corn stover were explored.

Results: The results showed that the maximum adsorption capacity of Avicel reduced from 276.9 to 179.7 and 112.1 mg/g cellulose with the addition of 1 and 10 mg lignin per gram Avicel, which indicated that lignin adsorbed on Avicel reduced surface area of cellulose and lignin available for cellulases. Cellulases adsorbed on lignin could be released by reaching new adsorption equilibrium between lignin and supernatants. In addition, cellulases desorbed from lignin still possess hydrolytic capacity. Tween 80 could adsorb onto both lignin and corn stover, and reduce the cellulase adsorption on them. Furthermore, Tween 80 could enhance desorption of cellulases from both lignin and corn stover, which might be due to the competitive adsorption between cellulases and Tween 80 on them.

Conclusions: The presence of lignin decreased the maximum adsorption capacity of cellulases on cellulose and the cellulases adsorbed on lignin could be released to supernatant, exhibiting hydrolytic activity. Tween 80 could alleviate the adsorption of cellulases and enhanced desorption of cellulases on/from lignin and corn stover. The conclusions of this work help us further understanding the role of lignin in the reduction of adsorption of cellulases on substrates, and the function of additives in cellulases adsorption and desorption on/from lignin and substrates.
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http://dx.doi.org/10.1186/s13068-016-0434-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727347PMC
January 2016

Missense-depleted regions in population exomes implicate ras superfamily nucleotide-binding protein alteration in patients with brain malformation.

NPJ Genom Med 2016 5;1. Epub 2016 Oct 5.

Department of Pediatrics, Division of Medical Genetics, University of California San Francisco, San Francisco, CA, USA.

Genomic sequence interpretation can miss clinically relevant missense variants for several reasons. Rare missense variants are numerous in the exome and difficult to prioritise. Affected genes may also not have existing disease association. To improve variant prioritisation, we leverage population exome data to identify intragenic missense-depleted regions (MDRs) genome-wide that may be important in disease. We then use missense depletion analyses to help prioritise undiagnosed disease exome variants. We demonstrate application of this strategy to identify a novel gene association for human brain malformation. We identified missense variants that affect the GDP/GTP-binding site of in three unrelated patients. Corresponding functional analysis suggests ARF1 GDP/GTP-activation is affected by the specific missense mutations associated with heterotopia. These findings expand the genetic pathway underpinning neurologic disease that classically includes . along with add further evidence implicating ARF/GEFs in the brain. Using functional ontology, top MDR-containing genes were highly enriched for nucleotide-binding function, suggesting these may be candidates for human disease. Routine consideration of MDR in the interpretation of exome data for rare diseases may help identify strong genetic factors for many severe conditions, infertility/reduction in reproductive capability, and embryonic conditions contributing to preterm loss.
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http://dx.doi.org/10.1038/npjgenmed.2016.36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576364PMC
October 2016

[Outcome of acute myeloid leukemia patients with normal karyotype].

Zhonghua Xue Ye Xue Za Zhi 2015 Aug;36(8):692-5

Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.

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http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2015.08.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348263PMC
August 2015

[Efficacy and safety of anagrelide in treatment of essential thrombocythemia: multicenter, randomized controlled clinical trial].

Zhonghua Xue Ye Xue Za Zhi 2015 Jul;36(7):547-52

Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.

Objective: To evaluate the efficacy and safety of anagrelide in essential thrombocythemia (ET).

Methods: Patients who diagnosed as ET according to the World Health Organization classification were enrolled. Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1∶1 ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to (100-400) × 10⁹/L, one month later gradually reduced to maintain dose. The dose of hydroxyurea was 1000 mg/d at beginning, then increased gradually, when platelet counts dropped to (100-400)×10⁹/L and kept for one month, reduced to maintain dose as 10 mg·kg⁻¹·d⁻¹. The observation period was 12 weeks.

Results: A total of 222 patients were enrolled in seventeen centers (including 113 patients treated with anagrelide and 109 with hydroxyurea). Therapy efficacy can be evaluated in 198 patients (including 97 patients administered with anagrelide and 101 with hydroxyurea). At 12th weeks of therapy, the hematologic remission rate was 87.63% (85/97) in anagrelide group and 88.12% (89/107) in hydroxyurea group, the differences between the two groups were not significant (P=0.173). Treatment with anagrelide lowered the platelet counts by a median of 393 (362-1 339) × 10⁹/L from a median of 827 (562-1657) × 109/L at the beginning of the observation to 400(127-1130)×10⁹/L after 12 weeks (P<0.001), which were similar to the treatment result of hydroxyurea by a median drop of 398 (597-1846)× 10⁹/L (P=0.982). The median time to achieving response of anagrelide group was 7 (3-14) days, superior to that of hydroxyurea for 21 (14-28) significantly (P=0.003). Frequency of anagrelide related adverse events was 65.49 % (74/113), including cardiopalmus (36.28% ), headache (21.24% ), fatigue (14.16% ) and dizzy (11.50% ).

Conclusion: Anagrelide was effective in patients with ET which had similar hematologic remission rate to hydroxyurea and could take effect more quickly than hydroxyurea. Incidence of adverse events was undifferentiated between anagrelide and hydroxyurea, but anagrelide treatment had tolerable adverse effects and no hematologic toxicity.
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http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2015.07.00DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342634PMC
July 2015

Effect of additives on adsorption and desorption behavior of xylanase on acid-insoluble lignin from corn stover and wheat straw.

Bioresour Technol 2015 Jun 19;186:316-320. Epub 2015 Mar 19.

College of Forestry, Northwest A&F University, 3 Taicheng Road, Yangling 712100, China. Electronic address:

The competitive adsorption between cellulases and additives on lignin in the hydrolysis of lignocelluloses has been confirmed, whereas the effect of additives on the interaction between xylanase and lignin is not clear. In this work, the effects of additives, poly(ethylene glycol) 2000, poly(ethylene glycol) 6000, Tween 20, and Tween 80, on the xylanase adsorption/desorption onto/from acid-insoluble lignin from corn stover (CS-lignin) and wheat straw (WS-lignin) were investigated. The results indicated that the additives could adsorb onto isolated lignin and reduce the xylanase adsorption onto lignin. Compared to CS-lignin, more additives could adsorb onto WS-lignin, making less xylanase adsorbed onto WS-lignin. In addition, the additives could enhance desorption of xylanase from lignin, which might be due to the competitive adsorption between xylanase and additives on lignin. The released xylanase from lignin still exhibited hydrolytic capacity in the hydrolysis of isolated xylan and xylan in corn stover.
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http://dx.doi.org/10.1016/j.biortech.2015.03.058DOI Listing
June 2015

Competitive inhibition of cellobiohydrolase I by manno-oligosaccharides.

Enzyme Microb Technol 2015 Jan 30;68:62-8. Epub 2014 Sep 30.

College of Forestry, Northwest A&F University, 3 Taicheng Road, Yangling 712100, China. Electronic address:

In the hydrolysis of softwood, significant amounts of manno-oligosaccharides (MOS) are released from mannan, the major hemicelluloses in softwood. However, the impact of MOS on the performance of cellulases is not yet clear. In this work, the effect of mannan and MOS in cellulose hydrolysis by cellulases, especially cellobiohydrolase I (CBHI) from Thermoascus aurantiacus (Ta Cel7A), was studied. The glucose yield of Avicel decreased with an increasing amount of added mannan. Commercial cellulases contained mannan hydrolysing enzymes, and β-glucosidase played an important role in mannan hydrolysis. Addition of 10mg/ml mannan reduced the glucose yield of Avicel (at 20g/l) from 40.1 to 24.3%. No inhibition of β-glucosidase by mannan was observed. The negative effects of mannan and MOS on the hydrolytic action of cellulases indicated that the inhibitory effect was at least partly attributed to the inhibition of Ta Cel7A (CBHI), but not on β-glucosidase. Kinetic experiments showed that MOS were competitive inhibitors of the CBHI from T. aurantiacus, and mannobiose had a stronger inhibitory effect on CBHI than mannotriose or mannotetraose. For efficient hydrolysis of softwood, it was necessary to add supplementary enzymes to hydrolyze both mannan and MOS to less inhibitory product, mannose.
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http://dx.doi.org/10.1016/j.enzmictec.2014.09.009DOI Listing
January 2015

Prioritizing genes for X-linked diseases using population exome data.

Hum Mol Genet 2015 Feb 12;24(3):599-608. Epub 2014 Sep 12.

Division of Medical Genetics, Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA

Many new disease genes can be identified through high-throughput sequencing. Yet, variant interpretation for the large amounts of genomic data remains a challenge given variation of uncertain significance and genes that lack disease annotation. As clinically significant disease genes may be subject to negative selection, we developed a prediction method that measures paucity of non-synonymous variation in the human population to infer gene-based pathogenicity. Integrating human exome data of over 6000 individuals from the NHLBI Exome Sequencing Project, we tested the utility of the prediction method based on the ratio of non-synonymous to synonymous substitution rates (dN/dS) on X-chromosome genes. A low dN/dS ratio characterized genes associated with childhood disease and outcome. Furthermore, we identify new candidates for diseases with early mortality and demonstrate intragenic localized patterns of variants that suggest pathogenic hotspots. Our results suggest that intrahuman substitution analysis is a valuable tool to help prioritize novel disease genes in sequence interpretation.
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http://dx.doi.org/10.1093/hmg/ddu473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291241PMC
February 2015

Four SNPs in the CHRNA3/5 alpha-neuronal nicotinic acetylcholine receptor subunit locus are associated with COPD risk based on meta-analyses.

PLoS One 2014 22;9(7):e102324. Epub 2014 Jul 22.

School of Public Health, Liaoning Medical University, Jinzhou, Liaoning, P.R. China.

Background: Several single nucleotide polymorphisms (SNPs) in an α-neuronal nicotinic acetylcholine receptor subunit (CHRNA3/5) were identified to be associated with chronic obstructive pulmonary disease (COPD) in a study based on a Norwegian population. However, results from subsequent studies have been controversial, particularly in studies recruiting Asians. In the present study, we conducted a comprehensive search and meta-analyses to identify susceptibility SNPs for COPD in the CHRNA3/5 locus.

Methods: A comprehensive literature search was conducted to find studies that have reported an association between SNPs in the CHRNA3/5 locus and COPD risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for each SNP were calculated with the major allele or genotype as the reference group. The influence of individual studies on pooled measures was assessed, in addition to publication bias.

Results: A total of 12 articles with 14 eligible studies were included in this analysis. Association between 4 SNPs in the CHRNA3/5 locus and COPD was evaluated and included rs1051730, rs8034191, rs6495309, and rs16969968. Significant associations between the 4 SNPs and COPD were identified under allele (rs1051730: OR = 1.14, 95%CI = 1.10-1.18; rs8034191: OR = 1.29, 95%CI = 1.18-1.41; rs6495309: OR = 1.26, 95%CI = 1.09-1.45; rs16969968: OR = 1.27, 95%CI = 1.17-1.39) and genotype models. Subgroup analysis conducted for rs1051730 showed a significant association between this SNP and COPD risk in non-Asians (OR = 1.14, 95%CI = 1.10-1.18), but not Asians (OR = 1.23, 95%CI = 0.91-1.67). Rs1051730 and rs6495309 were also significantly associated with COPD after adjusting for multiple variables, including age and smoking status.

Conclusion: Our results indicate that 4 SNPs in the CHRNA3/5 locus are associated with COPD risk. Rs1051730 was particularly associated with COPD in non-Asians, but its role in Asians still needs to be verified. Additional studies will be necessary to assess the effect of rs6495309 on COPD. Although rs1051730 and rs6495309 were shown to be independent risk factors for COPD, validation studies should be performed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102324PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106784PMC
March 2016
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