Comprehensive understanding of glioblastoma molecular phenotypes:classification,characteristics,and transition

Among central nervous system-associated malignancies,glioblastoma(GBM)is the most common and has the highest mortality rate.The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide.In precision medicine,research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity,as well as the refractory nature of GBM toward therapy.Deep understanding of the different molecular expression patterns of GBM subtypes is critical.Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes.The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors.These subtypes also exhibit high plasticity in their regulatory pathways,oncogene expression,tumor microenvironment alterations,and differential responses to standard therapy.Herein,we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype.Furthermore,we review the mesenchymal transition mechanisms of GBM under various regulators.

Identification of clinical subphenotypes of sepsis after laparoscopic surgery

Objective:Some patients exhibit septic symptoms following laparoscopic surgery,leading to a poor prognosis.Effective clinical subphenotyping is critical for guiding tailored therapeutic strategies in these cases.By identifying predisposing factors for postoperative sepsis,clinicians can implement targeted interventions,potentially improving outcomes.This study outlines a workflow for the subphenotype methodology in the context of laparoscopic surgery,along with its practical application.Methods:This study utilized data routinely available in clinical case systems,enhancing the applicability of our findings.The data included vital signs,such as respiratory rate,and laboratory measures,such as blood sodium levels.The process of categorizing clinical routine data involved technical complexities.A correlation heatmap was used to visually depict the relationships between variables.Ordering points were used to identify the clustering structure and combined with Consensus K clustering methods to determine the optimal categorization.Results:Our study highlighted the intricacies of identifying clinical subphenotypes following laparoscopic surgery,and could thus serve as a valuable resource for clinicians and researchers seeking to explore disease heterogeneity in clinical settings.By simplifying complex methodologies,we aimed to bridge the gap between technical expertise and clinical application,fostering an environment where professional medical knowledge is effectively utilized in subphenotyping research.Conclusion:This tutorial could primarily serve as a guide for beginners.A variety of clustering approaches were explored,and each step in the process contributed to a comprehensive understanding of clinical subphenotypes.

Classification of congenital cataracts based on multidimensional phenotypes and its association with visual outcomes

●AIM:To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes.●METHODS:Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited.Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients’medical records.A hierarchical cluster analysis was performed.The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts.●RESULTS:A total of 164 children(299 eyes)were divided into two clusters based on their ocular features.Cluster 1(96 eyes)had a shorter axial length(mean±SD,19.44±1.68 mm),a low prevalence of macular abnormalities(1.04%),and no retinal abnormalities or posterior cataracts.Cluster 2(203 eyes)had a greater axial length(mean±SD,20.42±2.10 mm)and a higher prevalence of macular abnormalities(8.37%),retinal abnormalities(98.52%),and posterior cataracts(4.93%).Compared with the eyes in Cluster 2(57.14%),those in Cluster 1(71.88%)had a 2.2 times higher chance of good best-corrected visual acuity[<0.7 logMAR;OR(95%CI),2.20(1.25–3.81);P=0.006].●CONCLUSION:This retrospective study categorizes congenital cataracts into two distinct clusters,each associated with a different likelihood of visual outcomes.This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit,thereby making strides toward precision medicine in the field of congenital cataracts.

Association between the Different Phenotypes of Polycystic Ovary Syndrome and the Outcome in in Vitro Fertilization at Human Reproductive Center Paul et Chantal Biya-Yaoundé

Background: In Vitro Fertilization/Intracytoplasmic Sperm Injection (IVF/ICSI) represents the final step in the management of Polycystic Ovarian Syndrome (PCOS). Our objective was to study the association between PCOS phenotypes and IVF/ICSI results in women admitted to Gynaecological Endoscopic Surgery and Human Reproductive Teaching Hospital (CHRACERH). Material and Method: We carried out a cohort study with historical-prospective data collection over a period of seven years (January 2016 to March 2023) at Chracerh. PCOS patients were subdivided into 4 subgroups A, B, C and D. Results: We recruited 128 patients including 64 PCOS patients divided into four phenotypes and 64 non-PCOS patients constituting the control group. Phenotype D without hyperandrogenism had used the lowest dose of gonadotropins, i.e. 1939.7 ± 454.3 IU, and had produced a greater quantity of estradiol on the day ovulation was triggered (6529.8 ± 4324.8 ng/ml). The average number of punctured follicles and mature oocytes were higher in the phenotype D group. Ovarian hyperstimulation syndrome (OHSS) occurred mainly in phenotype D (3/35), with an estimated prevalence of 2.3%. The fertilization rate seemed lower in the hyperandrogenic phenotypes A, B, C compared to the group without hyperandrogenism without significant difference (p = 0.461). The biological pregnancy rate and live birth rate were comparable between the different groups. Conclusion: Phenotype D used less dose of gonadotropins. Biological pregnancy and live birth rates were comparable between the different phenotypes.

LncRNA CACNA1G-AS1 up-regulates FTH1 to inhibit ferroptosis and promote malignant phenotypes in ovarian cancer cells

Previous study revealed that ferritin heavy chain-1(FTH1)could regulate ferritinophagy and affect intracellular Fe^(+)content in various tumors,while its N6-methyladenosine(m6A)RNA methylation was closely related the prognosis of ovarian cancer patients.However,little is known about the role of FTH1 m6A methylation in ovarian cancer(OC)and its possible action mechanisms.In this study we constructed FTH1 m6A methylation regulatory pathway(LncRNA CACNA1G-AS1/IGF2BP1)according to related bioinformatics analysis and research,through clinical sample detections we found that these pathway regulatory factors were significantly up-regulated in ovarian cancer tissues,and their expression levels were closely related to the malignant phenotype of ovarian cancer.In vitro cell experiments showed that LncRNA CACNA1G-AS1 could up-regulate FTH1 expression through IGF2BP1 axis,thus inhibited ferroptosis by regulating ferritinophagy,and finally promoted proliferation and migration in ovarian cancer cells.Tumor-bearing mice studies showed that the knock-down of LncRNA CACNA1G-AS1 could inhibited the tumorigenesis of ovarian cancer cells in vivo condition.Our results demonstrated that LncRNA CACNA1G-AS1 could promote the malignant phenotypes of ovarian cancer cells through FTH1-IGF2BP1 regulated ferroptosis.

Mesenchymal stem cell-derived exosomes regulate microglia phenotypes:a promising treatment for acute central nervous system injury

There is growing evidence that long-term central nervous system(CNS)inflammation exacerbates secondary deterioration of brain structures and functions and is one of the major determinants of disease outcome and progression.In acute CNS injury,brain microglia are among the first cells to respond and play a critical role in neural repair and regeneration.However,microglial activation can also impede CNS repair and amplify tissue damage,and phenotypic transformation may be responsible for this dual role.Mesenchymal stem cell(MSC)-derived exosomes(Exos)are promising therapeutic agents for the treatment of acute CNS injuries due to their immunomodulatory and regenerative properties.MSC-Exos are nanoscale membrane vesicles that are actively released by cells and are used clinically as circulating biomarkers for disease diagnosis and prognosis.MSC-Exos can be neuroprotective in several acute CNS models,including for stroke and traumatic brain injury,showing great clinical potential.This review summarized the classification of acute CNS injury disorders and discussed the prominent role of microglial activation in acute CNS inflammation and the specific role of MSC-Exos in regulating pro-inflammatory microglia in neuroinflammatory repair following acute CNS injury.Finally,this review explored the potential mechanisms and factors associated with MSCExos in modulating the phenotypic balance of microglia,focusing on the interplay between CNS inflammation,the brain,and injury aspects,with an emphasis on potential strategies and therapeutic interventions for improving functional recovery from early CNS inflammation caused by acute CNS injury.

Identification of tolerance to high density and lodging in short petiolate germplasm M657 and the effect of density on yield-related phenotypes of soybean

Soybean yield has traditionally been increased through high planting density,but investigating plant height and petiole traits to select for compact architecture,lodging resistance,and high yield varieties is an underexplored option for further improving yield.We compared the relationships between yield-related traits,lodging resistance,and petioleassociated phenotypes in the short petiole germplasm M657 with three control accessions during 2017–2018 in four locations in the Huang–Huai region,China.The results showed that M657 exhibited stable and high tolerance to high planting density and resistance to lodging,especially at the highest density(8×105 plants ha–1).The regression analysis indicated that a shorter petiole length was significantly associated with increased lodging resistance.The yield analysis showed that M657 achieved higher yields under higher densities,especially in the northern part of the Huang–Huai region.Among the varieties,there were markedly different responses to intra-and inter-row spacing designs with respect to both lodging and yield that were related to location and density.Lodging was positively correlated with planting density,plant height,petiole length,and number of effective branches,but negatively correlated with stem diameter,seed number per plant,and seed weight per plant.The yield of soybean was increased by appropriately increasing the planting density on the basis of the current soybean varieties in the Huang–Huai region.This study provides a valuable new germplasm resource for the introgression of compact architecture traits that are amenable to providing a high yield in high density planting systems,and it establishes a high-yield model of soybean in the Huang–Huai region.

Redefying the therapeutic strategies against cardiorenal morbidity and mortality:Patient phenotypes

Chronic kidney disease(CKD)patients face an unacceptably high morbidity and mortality,mainly from cardiovascular diseases.Diabetes mellitus,arterial hypertension and dyslipidemia are highly prevalent in CKD patients.Established therapeutic protocols for the treatment of diabetes mellitus,arterial hypertension,and dyslipidemia are not as effective in CKD patients as in the general population.The role of non-traditional risk factors(RF)has gained interest in the last decades.These entail the deranged clinical spectrum of secondary hyperparathyroidism involving vascular and valvular calcification,under the term“CKDmineral and bone disorder”(CKD-MBD),uremia per se,inflammation and oxidative stress.Each one of these non-traditional RF have been addressed in various study designs,but the results do not exhibit any applied clinical benefit for CKD-patients.The“crusade”against cardiorenal morbidity and mortality in CKD-patients is in some instances,derailed.We propose a therapeutic paradigm advancing from isolated treatment targets,as practiced today,to precision medicine involving patient phenotypes with distinct underlying pathophysiology.In this regard we propose two steps,based on current stratification management of corona virus disease-19 and sepsis.First,select patients who are expected to have a high mortality,i.e.,a prognostic enrichment.Second,select patients who are likely to respond to a specific therapy,i.e.,a predictive enrichment.

Phenotypic Detection of Enterobacterales Strains Susceptible of Producing OXA-48 Carbapenemase

Background: Nowadays, emergence of Carbapenemase-Producing Enterobacterales (CPE) throughout the world has become a public health problem, especially in countries with limited resources. In recent years, CPE of type OXA-48 (Ambler class D) have been identified in Dakar. The aim of this study was to evaluate the phenotypic detection of OXA-48 CPE using a temocillin disc (30 μg). Methodology: A retrospective study was carried out at Medical Biology Laboratory of Pasteur Institute in Dakar on Ertapenem-Resistant Enterobacterales (ERE) strains isolated from 2015 to 2017. These strains were then tested with a 30 μg temocillin disc. Any strain resistant to temocillin (inhibition diameter Results: Forty-one ERE isolated during the study period were tested, of which 34 (82.9%) were OXA-48 based on phenotypic detection using temocillin disc and confirmed by PCR (100%). OXA-48 CPE strains detected were composed of Klebsiella pneumoniae (n = 14;41.2%), Enterobacter cloacae (n = 8;23.5%), Escherichia coli (n = 7, 20.5%), Citrobacter freundii (n = 3;8.8%), Cronobacter sakazakii (n = 1;3%) and Morganella morganii (n = 1;3%). Conclusion: Temocillin resistance has a good positive predictive value for detecting OXA-48 CPE by phenotypic method, confirmed by PCR. Temocillin is therefore a good marker for detection of OXA-48 CPE except Hafnia alvei.

Phenotypic Characterization and QTL/Gene Identification for Internode Number and Length Related Traits in Maize

Internode number and length are the foundation to constitute plant height, ear height and the above-ground spatial structure of maize plant. In this study, segregating populations were constructed between EHel with extremely low ear height and B73. Through the SNP-based genotyping and phenotypic characterization, 13 QTL distributed on the chromosomes (Chrs) of Chr1, Chr2, Chr5-Chr8 were detected for four traits of internode no. above ear (INa), average internode length above ear (ILaa), internode no. below ear (INb), and average internode length below ear (ILab). Phenotypic variation explained (PVE) by a single QTL ranged from 6.82% (qILab2-2) to 12.99% (qILaa5). Zm00001d016823 within the physical region of qILaa5, the major QTL for ILaa with the largest PVE was determined as the candidate through the genomic annotation and sequence alignment between EHel and B73. Product of Zm00001d016823 was annotated as a WEB family protein homogenous to At1g75720. qRT-PCR assay showed that Zm00001d016823 highly expressed within the tissue of internode, exhibiting statistically higher expression levels among internodes of IN4 to IN7 in EHel than those in B73 (P Zm00001d016823 might provide novel insight into molecular mechanism beyond phytohormones controlling internode development in maize.

Integrating artificial intelligence and high-throughput phenotyping for crop improvement

Crop improvement is crucial for addressing the global challenges of food security and sustainable agriculture.Recent advancements in high-throughput phenotyping(HTP)technologies and artificial intelligence(AI)have revolutionized the field,enabling rapid and accurate assessment of crop traits on a large scale.The integration of AI and machine learning algorithms with HTP data has unlocked new opportunities for crop improvement.AI algorithms can analyze and interpret large datasets,and extract meaningful patterns and correlations between phenotypic traits and genetic factors.These technologies have the potential to revolutionize plant breeding programs by providing breeders with efficient and accurate tools for trait selection,thereby reducing the time and cost required for variety development.However,further research and collaboration are needed to overcome the existing challenges and fully unlock the power of HTP and AI in crop improvement.By leveraging AI algorithms,researchers can efficiently analyze phenotypic data,uncover complex patterns,and establish predictive models that enable precise trait selection and crop breeding.The aim of this review is to explore the transformative potential of integrating HTP and AI in crop improvement.This review will encompass an in-depth analysis of recent advances and applications,highlighting the numerous benefits and challenges associated with HTP and AI.

A Comprehensive Overview of Skeletal Phenotypes Associated with Alterations in Wnt/β-catenin Signaling in Humans and Mice

The Wnt signaling pathway plays key roles in differentiation and development and alterations in this signaling pathway are causally associated with numerous human diseases. While several laboratories were examining roles for Wnt signaling in skeletal development during the 1990s, interest in the pathway rose exponentially when three key papers were published in 2001-2002. One report found that loss of the Wnt co-receptor, Low-density lipoprotein related protein-5 （LRPS）, was the underlying genetic cause of the syndrome Osteoporosis pseudoglioma （OPPG）. OPPG is characterized by early-onset osteoporosis causing increased susceptibility to debilitating fractures. Shortly thereafter, two groups reported that individuals carrying a specific point mutation in LRP5 （G171V） develop high-bone mass. Subsequent to this, the causative mechanisms for these observations heightened the need to understand the mechanisms by which Wnt signaling controlled bone development and homeostasis and encouraged significant investment from biotechnology and pharmaceutical companies to develop methods to activate Wnt signaling to increase bone mass to treat osteoporosis and other bone disease. In this review, we will briefly summarize the cellular mechanisms underlying Wnt signaling and discuss the observations related to OPPG and the high-bone mass disorders that heightened the appreciation of the role of Wnt signaling in normal bone development and homeostasis. We will then present a comprehensive overview of the core components of the pathway with an emphasis on the phenotypes associated with mice carrying genetically engineered mutations in these genes and clinical observations that further link alterations in the pathway to changes in human bone.

Morphological diversity and correlation analysis of phenotypes and quality traits of proso millet(Panicum miliaceum L.)core collections

Genetic diversity and comprehensive performance are the basis for the discovery and efficient use of proso millet(Panicum miliaceum L.) core collections. In this study, 386 proso millet core collections were used as materials to observe inflorescence color, leaf phase, inflorescence density, axis shape, branched spike length, panicle type, trichome, measured area of the top3 leaves, and chlorophyll content of the top3 leaves at filling stage. These core collections were also used to record growth period, plant height, diameter of main stem, plant tiller number, branch number, panicle length, panicle number per plant, and panicle weight per plant at the maturation stage. Starch, fat, protein, and yellow pigment contents in the grain and 1 000-seed weight were also measured after harvest. Then, quantitative traits were used for diversity analysis and comprehensive evaluation of each collection. Correlations between all traits were also analyzed. Results showed that among the 8 quality traits, the Shannon index(H′) of hull color was the highest(1.588) followed by the H′ of inflorescence density(0.984). However, inflorescence color and axis shape were lower. The H′ of 16 quantitative traits were significantly higher than the quality traits with the following traits having the highest indices: fat content(2.092), 1 000-seed weight(2.073), top3 leaves area(2.070), main stem diameter(2.056), and plant height(2.052). Furthermore, all other traits had a diversity higher than 1.900. After a comprehensive evaluation of phenotypic traits, plant height, diameter of main stem, plant tiller number, leaf area of top3 leaves, and 1 000-seed weight were the biggest contributors to the principal components. Six high-fat and high-protein cultivars, including Nuoshu, A75-2, Zhiduoaosizhi, Panlonghuangmi, Xiaobaishu, and Xiaohongshu were also screened. Correlations between the quantitative traits were significant, including the correlation between quality traits and quantitative traits. In conclusion, the core collections can be used as basis for discriminating among proso millet cultivars based on related traits and for further studies on millet with rich genetic diversity, good representation, and significant collection between traits.

Effects of Thermal and Hydric Conditions on Egg Incubation and Hatchling Phenotypes in Two Phrynocephalus Lizards

Flexible-shelled eggs of the lizards Phrynocephalus przewalskii and P. versicolor were incubated under different thermal and hydric conditions to elicit the effects of incubation environment on hatching success, embryonic development and duration as well as hatchling phenotypes. Embryogenesis of the two species was not sensitive to changes in the hydric environment except P. przewalskii incubated in 30°C group. Temperature significantly altered the duration of embryogenesis, with cooler temperatures leading to a longer incubation period. Hatching success was greater at 26 and 30°C than at 34°C. The hatchlings incubated at 26 and 30°C had longer snout-vent length, larger body mass, and better locomotor performance than those incubated at 34°C. Compared to P. przewalskii, P. versicolor had a shorter incubation period and yielded smaller hatchlings, which then had a higher survival rate in cooler and drier habitats. We conclude that an incubation temperature of 30°C would produce the best balance among developmental rate, hatching success, and post-hatching performance. We speculate that the upper temperature limit for incubation of P. versicolor eggs may be slightly higher than 34°C.

Association of the Common Genetic Variant Upstream of INSIG2 Gene with Obesity Related Phenotypes in Chinese Children and Adolescents

Objective To study the association between the rs7566605 variant of INSIG2 and obesity-related phenotypes in Chinese children and adolescents. Methods The study sample consisted of two independent cohorts of Chinese children and adolescents. Anthropometric indices, lipids, blood pressure, fasting glucose, insulin and percentage of fat mass were determined. PCR with restriction fragment length polymorphism analysis was performed for genotyping the rs7566605 variant. Results In each of the two independent cohorts, no significant association was observed between rs7566605 and obesity under additive, dominant or recessive model. We also did not detect any difference in the genotype frequency between all the obese children and controls. Furthermore, we did not find evidence of an association between body composition indices and metabolic phenotypes in all children. However, the triglyceride level of CC homozygotes was significantly higher than that of GG＋GC genotypes in obese children （P=0.022）. Additionally, we observed a non-significant trend of severe obesity in a post-hoc test. Conclusion INSIG2 rs7566605 variant is not associated Chinese childhood obesity in two independent cohorts. Further study is needed to verify the effect of rs7566605 on triglyceride in obese children.

Relationship between clinicopathological features and mucin phenotypes of advanced gastric adenocarcinoma

AIM: To investigate a relationship between the clinicopathological features and mucin phenotypes in advanced gastric adenocarcinoma (AGA). METHODS: Immunohistochemical staining was performed to determine the mucin phenotypes in 38 patients with differentiated adenocarcinomas (DACs), 9 with signet-ring cell carcinomas (SIGs), and 48 with other diffuse-type adenocarcinomas (non-SIGs) of AGA. The mucin phenotypes were classified into 4 types: gastric (G), gastrointestinal (GI), intestinal, and unclassified. RESULTS: The G-related mucin phenotypes were highly expressed in all the histological subtypes of AGA. The expression of the GI phenotype in SIG patients was lower than that in DAC patients (P = 0.02), and this phenotype was observed in 56% of the non-SIG patients in the intramucosal layer. Among non-SIG cases, the expression of the GI phenotype was significantly higherin patients with extended adenocarcinomas and those with positive rates of lymph node metastasis. There was no difference between the expressions of the G and other GI phenotypes factors. Among DAC and non-SIG patients, there were no differences between the survival rates of the corresponding patient groups. CONCLUSION: The GI phenotype might possess more invasive characteristics than the G phenotype in nonSIG. Neither of the phenotypes indicated a poor prognosis of DAC and non-SIG.

Immunogenetic phenotypes in inflammatory bowel disease

The currently accepted etiopathogenic hypothesis suggests that the chronic intestinal inflammation and related systemic manifestations characteristic of inflammatory bowel disease （IBD） are due to an overly aggressive or pathologic immune response to resident luminal bacterial constituents. Predisposing factors are genetic dysregulation of mucosal immune responses and/ or barrier function, with onset triggered by environmental stimuli. These factors and their interactions may also be important determinants of disease phenotype and disease progression. The emergence of immunogenetic phenotypes lends support to the proposed hypothesis that susceptibility genes regulate distinct immune processes, driven by luminal antigens, expressed as specific immune phenotypes which in turn influence clinical phenotypes in IBD patient.

Non-classical phenotypes of autoimmune hepatitis and advances in diagnosis and treatment

Non-classical manifestations of autoimmune hepatitis can delay diagnosis and treatment. Our aims were to describe the clinical phenotypes that can confound the diagnosis, detail scoring systems that can ensure their recognition, and outline advances in treatment that can improve their outcome. Prime source and review articles in English were selected throuqh Medline from 1970-2008 and assimilated into personal libraries spanning 32 years. Acute severe or asymptomatic presentations and atypical histological findings,including centrilobular zone 3 necrosis and concurrent bile duct changes, are compatible with the diagnosis. Cholangiographic abnormalities may be present in children and adults with the disease, and autoimmune hepatitis must be considered in patients without autoantibodies or with antimitochondrial antibodies and no other cholestatic features. Asymptomatic patients frequently become symptomatic; mild disease can progress; and there are no confident indices that justify withholding treatment. Two diagnostic scoring systems with complementary virtues have been developed to evaluate patients with confusing features. Normal liver tests and tissue constitute the optimal end point of treatment, and the first relapse is an indication for long- term azathioprine therapy. Cyclosporine, tacrolimus and mycophenolate mofetil are promising salvage therapies,and budesonide with azathioprine may be a superior frontline treatment. We conclude that the non-classical phenotypes of autoimmune hepatitis can be recognized promptly, diagnosed accurately, and treated effectively.

Relationship Between Blast Resistance Phenotypes and Resistance Gene Analogue Profiles in Rice

A total of 21 rice varieties were assayed based on RGA-PCR using six pairs of RGA primers and evaluated for leaf blast resistance in the nursery as well. Cluster analysis showed that the varieties could be classified into five groups either at the similarity threshold of 0.72 for RGA profiles or at 0.80 for leaf blast severities. Although there did not exist a complete parallel relationship between RGA-based groups and blast resistance-based groups, five out of six varieties with broad spectrum or durable resistance repeatedly fell into same group. This result suggested that application of three primer pairs, viz. RGA1 and RGA2 （both designed from the LRR region of rice Xa21 gene） and RGA3 （designed from the LRR region of tobacco N gene） contributed to better evaluation of the germplasms for their resistance responses to rice blast.

Pathway-based analysis of genome-wide association study of circadian phenotypes

Sleepiness affects normal social life, which attracts more and more attention. Circadian phenotypes contribute to obvious individual differences in susceptibility to sleepiness. We aimed to identify candidate single nucleotide polymorphisms（SNPs） which may cause circadian phenotypes, elucidate the potential mechanisms, and generate corresponding SNP-gene-pathways. A genome-wide association studies（GWAS） dataset of circadian phenotypes was utilized in the study. Then, the Identify Candidate Causal SNPs and Pathways analysis was employed to the GWAS dataset after quality control filters. Furthermore, genotype-phenotype association analysis was performed with HapMap database. Four SNPs in three different genes were determined to correlate with usual weekday bedtime,totally providing seven hypothetical mechanisms. Eleven SNPs in six genes were identified to correlate with usual weekday sleep duration, which provided six hypothetical pathways. Our results demonstrated that fifteen candidate SNPs in eight genes played vital roles in six hypothetical pathways implicated in usual weekday bedtime and six potential pathways involved in usual weekday sleep duration.