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Genome-wide association studies: inherent limitations and future challenges

null

《医学前沿（英文）》 2012年 第6卷 第4期   页码 444-450 doi: 10.1007/s11684-012-0225-3

摘要：

Genome-wide association studies (GWAS) have achieved great success in identifying genetic variants related to complex human diseases such as cancer and have provided valuable insights into their genetic architecture. Recently, GWAS is quite the fashion in China. However, there are issues related to its nature. Enormous work needs to be done in the post-GWAS era. Deep sequencing followed by functional studies will be needed to elucidate the underpinning biological mechanisms and further translate GWAS findings into medical practice. Along with pharmacogenomics, the success of GWAS in identifying genetic risk factors and genetic differences in drug response has been gradually enabling personalized medicine. In this article, we used hepatocellular carcinoma (HCC) as an example to demonstrate some of the inherent limitations and summarized future challenges of GWAS.

关键词： genome-wide association studies (GWAS)     genetic variant     cancer     limitation     challenge    

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Advancement in genetic variants conferring obesity susceptibility from genome-wide association studies

null

《医学前沿（英文）》 2015年 第9卷 第2期   页码 146-161 doi: 10.1007/s11684-014-0373-8

摘要：

Obesity prevalence has increased in recent years. Lifestyle change fuels obesity, but genetic factors cause more than 50% of average variations in obesity. The advent of genome-wide association studies (GWAS) has hastened the progress of polygenic obesity research. As of this writing, more than 73 obesity susceptibility loci have been identified in ethnic groups through GWAS. The identified loci explain only 2% to 4% of obesity heritability, thereby indicating that a large proportion of loci remain undiscovered. Thus, the next step is to identify and confirm novel loci, which may exhibit smaller effects and lower allele frequencies than established loci. However, achieving these tasks has been difficult for researchers. GWAS help researchers discover the causal loci. Moreover, numerous biological studies have been performed on the polygenic effects on obesity, such as studies on fat mass- and obesity-associated gene (FTO), but the role of these polygenic effects in the mechanism of obesity remains unclear. Thus, obesity-causing variations should be identified, and insights into the biology of polygenic effects on obesity are needed.

关键词： obesity     genetics     genome-wide association studies     body mass index     fat mass- and obesity-associated gene    

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关联规则挖掘算法综述

毕建欣,张岐山

《中国工程科学》 2005年 第7卷 第4期   页码 88-94

摘要：

介绍了关联规则挖掘算法的基本原理，并按照挖掘中涉及到的变量数目（维数）、数据的抽象层次和处理变量的类别（布尔型和数值型），依次对关联规则挖掘算法的研究进行综述，并对一些典型的算法进行分析和比较，最后展望了关联规则挖掘算法的研究方向。

关键词： 数据挖掘     关联规则     算法     综述    

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Obesity and overweight prevalence and its association with undiagnosed hypertension in Shanghai population

null

《医学前沿（英文）》 2012年 第6卷 第3期   页码 322-328 doi: 10.1007/s11684-012-0204-8

摘要：

The aim of this study was to determine the prevalence of overweight and obese subjects in the Shanghai population of China and its association with undiagnosed hypertension, by taking age, gender and place of residence (urban or suburban) into account. A cross-sectional population-based survey was conducted in 2007. The sample included 13 359 participants aged 15–69 years. Weight, height, and blood pressure were recorded, and information about gender, age and place of residence was obtained. Overweight and obesity prevalence were calculated by the body mass index (BMI) definition recommended by Working Group on Obesity in China (normal weight, 18.5–23.9 kg/m2; overweight, 24–27.9 kg/m2; obesity,≥28 kg/m2). Undiagnosed hypertension was defined by China criteria in accord with that of WHO-ISH (subjects with systolic pressure≥140 mmHg, and/or diastolic pressure≥90 mmHg). Multiple logistic regression analyses were used to assess the association of overweight or obesity with undiagnosed hypertension by adjusting for age, gender and place of residence. The overall overweight, obesity, and undiagnosed hypertension prevalence were 27.6% (95% CI: 26.8–28.4), 6.6% (95% CI: 6.2–7.0), and 15.5% (95% CI: 14.9–16.1), respectively. Compared to normal weight subjects, the odds ratios (OR) for subjects who were overweight and had hypertension was 2.33 (95% CI: 2.10–2.59); that for obesity and hypertension was 4.27 (95% CI: 3.66–4.99). These data suggest that overweight and obesity prevalence and their association with undiagnosed hypertension are high in our study population.

关键词： overweight     obesity     undiagnosed hypertension     prevalence     association    

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Genome-wide association study of the backfat thickness trait in two pig populations

Dandan ZHU,Xiaolei LIU,Rothschild MAX,Zhiwu ZHANG,Shuhong ZHAO,Bin FAN

《农业科学与工程前沿（英文）》 2014年 第1卷 第2期   页码 91-95 doi: 10.15302/J-FASE-2014005

摘要： Backfat thickness is a good predictor of carcass lean content, an economically important trait, and a main breeding target in pig improvement. In this study, the candidate genes and genomic regions associated with the tenth rib backfat thickness trait were identified in two independent pig populations, using a genome-wide association study of porcine 60K SNP genotype data applying the compressed mixed linear model (CMLM) statistical method. For each population, 30 most significant single-nucleotide polymorphisms (SNPs) were selected and SNP annotation implemented using Build 10.2. In the first population, 25 significant SNPs were distributed on seven chromosomes, and SNPs on SSC1 and SSC7 showed great significance for fat deposition. The most significant SNP (ALGA0006623) was located on SSC1, upstream of the gene. In the second population, 27 significant SNPs were recognized by annotation, and 12 SNPs on SSC12 were related to fat deposition. Two haplotype blocks, M1GA0016251-MARC0075799 and ALGA0065251-MARC0014203-M1GA0016298-ALGA0065308, were detected in significant regions where the and genes were identified as contributing to fat metabolism. The results indicated that genetic mechanism regulating backfat thickness is complex, and that genome-wide associations can be affected by populations with different genetic backgrounds.

关键词： backfat thickness     SNP chip     genome-wide association study     compressed mixed linear model     pig    

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How to judge the association of postmenopausal hormone therapy and the risk of breast cancer

Ling XU

《医学前沿（英文）》 2010年 第4卷 第3期   页码 290-293 doi: 10.1007/s11684-010-0093-7

摘要： The relevance of postmenopausal hormone therapy (HT) for breast cancer risk has been long debated, although it is one of the most important barriers for women to accept HT. Various opinions have been reported from recent randomized clinical trials and epidemiological studies. These unanswered questions include: whether HT has a positive impact on breast cancer; whether risks of therapy with unopposed estrogen and combined estrogen-progestin are different; and whether different types and routes of estrogen and progestogens, as well as the duration and cessation of HT use, have different impacts on this disorder. Recently, there has been some good news such as the following: the currently available data do not provide sufficient evidence to prove a causal relationship between postmenopausal HT and breast cancer; breast cancer in postmenopausal women using HT usually has better prognosis than that of nonusers. In conclusion, HT is still the most effective method of relieving climacteric symptoms for many postmenopausal women. However, a possible risk of breast cancer associated with long-term HT usage should not be ignored. With respect to prevention of breast cancer, regular evaluation of individual breast cancer susceptibility and close follow-up through mammography and/or breast sonography are necessary strategies for the safety of HT use.

关键词： breast cancer     postmenopausal hormone therapy     unopposed estrogen therapy     combined estrogen-progestin therapy    

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Abiotic association of phthalic acid esters with humic acid of a sludge landfill

Xiaoli CHAI, Yongxia HAO, Xin ZHAO, Guixiang LIU, Ying ZHU, Rong JI, Jun WU, Huanhuan TONG, Youcai ZHAO

《环境科学与工程前沿（英文）》 2012年 第6卷 第6期   页码 778-783 doi: 10.1007/s11783-012-0434-7

摘要： The abiotic association between phthalic acid esters (PAEs) and humic substances (HS) in sludge landfill plays an important role in the fate and stability of PAEs. An equilibrium dialysis combined with C-labeling was used to study the abiotic association of two abundant PAEs (diethyl phthalate and di- -butyl phthalate) with humic acid (HA) isolated from a sludge landfill with different stabilization times and different molecular weights. Elemental analysis and Fourier Transform Infrared Spectrophotometer (FTIR) suggested that high value of HA was related to the high aromatic content and large molecular weight of HA. The results indicated that the association strength of PAEs with HA depended on both the properties of the PAEs and the characteristics of HA. The values of the association were strongly dependent on solution pH, and decreased dramatically as the pH was increased from 3.0 to 9.0. The results suggested that non-specific hydrophobic interaction between PAEs and HA was the main contributor to the association of the PAEs with HA. The interactive hydrogen-bonds between the HA and the PAEs molecules may also be involved in the association.

关键词： abiotic association     phthalic acid esters (PAEs)     humic acid     sludge     landfill    

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Distribution of antibiotic resistance genes and their association with bacteria and viruses in decentralized

《环境科学与工程前沿（英文）》 2022年 第16卷 第3期 doi: 10.1007/s11783-021-1469-4

摘要：

• Distribution of ARGs in decentralized sewage facilities were investigated.

关键词： Decentralized sewage treatment facilities     Antibiotic resistance genes     Virus     Metagenomics     Network analysis    

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A post-GWAS replication study confirming the association of

Shaohua YANG,Chao QI,Yan XIE,Xiaogang CUI,Yahui GAO,Jianping JIANG,Li JIANG,Shengli ZHANG,Qin ZHANG,Dongxiao SUN

《农业科学与工程前沿（英文）》 2014年 第1卷 第4期   页码 321-330 doi: 10.15302/J-FASE-2014037

摘要： Genome-wide association studies with an Illumina Bovine50K chip have detected 105 SNPs associated with one or multiple milk production traits in the Chinese Holstein population. Of these, 38 significant SNPs detected with high confidence by both L1-TDT and MMRA methods were selected to further mine potential key genes affecting milk yield and milk composition. By blasting the flanking sequences of these 38 SNPs with the bovine genome sequence combined with comparative genomics analysis, 26 genes were found to contain or be near to such SNPs. Among them, the gene is merely 87 bp away from the significant SNP, Hapmap30383-BTC-005848. Hence, we report herein genotype-phenotype associations to further validate the genetic effects of the gene. By pooled DNA sequencing of 14 unrelated Holstein sires, a total of 18 with seven novel SNPs were identified. Among them, nine SNPs were in the 5′ regulatory region, one in exon 6 and the other in the 3′ UTR and 3′ regulatory region. A total of nine of these identified SNPs were successfully genotyped and analyzed by mass spectrometry for association with five milk production traits in an independent resource population. The results showed that these SNPs were statistically significant for more than two traits [ <(0.0001-0.0267)]. In addition, mRNA expression analyses revealed that was ubiquitous in eight different tissues, with a relatively higher expression level in the mammary gland than in other tissues. These findings, therefore, provide strong evidence for association of variants with milk yield and milk composition traits and may be applied in Chinese Holstein breeding programs.

关键词： GWAS     functional annotation     Chinese Holstein     milk production traits     C14H8orf33 gene     single nucleotide polymorphisms     association study    

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Genome-wide association analysis reveals genetic loci and candidate genes associated with intramuscular

Xingwang WANG, Rongrong DING, Jianping QUAN, Linxue YANG, Ming YANG, Enqin ZHENG, Dewu LIU, Gengyuan CAI, Zhenfang WU, Jie YANG

《农业科学与工程前沿（英文）》 2017年 第4卷 第3期   页码 335-341 doi: 10.15302/J-FASE-2017152

摘要： Intramuscular fat (IMF) is a major meat-quality trait in pigs. The content of IMF is directly associated with the taste and flavor of pork. As a complex trait, there could be multiple genes affecting IMF content in pork. Genome-wide association study is a powerful tool to detect genomic regions associated with phenotypic variations. The objectives of the present study were to identify or refine the positions of genomic regions affecting IMF, and to characterize candidate genes and pathways that may influence this trait. Of note, we identified a significant region in longissium dorsi muscle in a Duroc pig population for IMF content with PorcineSNP60 v2 BeadChip. This region spans 1.24 Mb on chromosome 8 and had been identified as a quantitative trait locus for IMF in Pietrain, Large White, Landrace, and Leicoma pigs. In this region, eight SNPs were significantly associated with IMF content. Three genes proximal to these significant SNPs were considered candidate genes, including , and . Our results confirm several previous findings and highlight several genes that may contribute to IMF variation in Duroc pigs.

关键词： Duroc pigs     genome-wide association analysis     intramuscular fat    

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Joint user association and resource partition for downlink-uplink decoupling in multi-tier HetNets Article

Zhi-yong FENG, Ze-bing FENG, T. Aaron GULLIVER

《信息与电子工程前沿（英文）》 2017年 第18卷 第6期   页码 817-829 doi: 10.1631/FITEE.1700031

摘要： 传统蜂窝网络要求移动用户上行和下行连接在相同基站上。然而，由于用户与基站发射功率存在差异，在不同无线环境下，将会导致用户从某基站接收到最强下行信号，但该基站并不能提供最强接收信号的上行链路。而且，由于大量机器设备接入蜂窝网络中，网络上行流量需求增大，从而导致基站下行和上行流量存在严重不对称。在多层异构蜂窝网络环境下，提出了基于上下行解耦的联合用户接入与资源划分模型。区别于现有用户接入异构蜂窝网络的准则，如基于最大用户接收功率和小区范围扩展，提出了基于联合博弈的机制以实现上下行解耦条件下的用户最优接入。对该机制的稳定性和收敛性作了证明，且证明其收敛到纳什均衡点的速率呈几何级数增长。此外，基于上述用户上下行接入的结果，得到了考虑用户公平性条件下的基站下行和上行最优带宽划分。仿真结果显示：相比现有其他用户接入策略，提出的机制有效地提升了网络速率。

关键词： 上下行解耦；用户接入；资源划分；异构蜂窝网络；联合博弈    

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U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control

null

《医学前沿（英文）》 2015年 第9卷 第4期   页码 478-486 doi: 10.1007/s11684-015-0420-0

摘要：

Telomeres play a critical role in biological ageing by maintaining chromosomal integrity and preventing chromosome ends fusion. Epidemiological studies have suggested that inter-individual differences of telomere length could affect predisposition to multiple cancers, but evidence regarding esophageal squamous cell carcinoma (ESCC) was still uncertain. Several telomere length-related single nucleotide polymorphisms (TL-SNPs) in Caucasians have been reported in genome-wide association studies. However, the effects of telomere length and TL-SNPs on ESCC development are unclear. Therefore, we conducted a case-control study (1045 ESCC cases and 1433 controls) to evaluate the associations between telomere length, TL-SNPs, and ESCC risk in Chinese population. As a result, ESCC cases showed overall shorter relative telomere length (RTL) (median: 1.34) than controls (median: 1.50, P<0.001). More interestingly, an evident nonlinear U-shaped association was observed between RTL and ESCC risk (P<0.001), with odds ratios (95% confidence interval) equal to 2.40 (1.84–3.14), 1.36 (1.03–1.79), 1.01 (0.76–1.35), and 1.37 (1.03–1.82) for individuals in the 1st (the shortest), 2nd, 3rd, and 5th (the longest) quintile, respectively, compared with those in the 4th quintile as reference group. No significant associations were observed between the eight reported TL-SNPs and ESCC susceptibility. These findings suggest that either short or extremely long telomeres may be risk factors for ESCC in the Chinese population.

关键词： esophageal squamous cell carcinoma     telomere length     genetic variants     susceptibility     genome-wide association study    

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J-shaped association between dietary zinc intake and new-onset hypertension: a nationwide cohort study

《医学前沿（英文）》 2023年 第17卷 第1期   页码 156-164 doi: 10.1007/s11684-022-0932-3

摘要： We aimed to investigate the relationship of dietary zinc intake with new-onset hypertension among Chinese adults. A total of 12,177 participants who were free of hypertension at baseline from the China Health and Nutrition Survey were included. Dietary intake was assessed by three consecutive 24-h dietary recalls combined with a household food inventory. Participants with systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or diagnosed by a physician or under antihypertensive treatment during the follow-up were defined as having new-onset hypertension. During a median follow-up duration of 6.1 years, 4269 participants developed new-onset hypertension. Overall, the association between dietary zinc intake and new-onset hypertension followed a J-shape (P for non-linearity < 0.001). The risk of new-onset hypertension significantly decreased with the increment of dietary zinc intake (per mg/day: hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.88–0.98) in participants with zinc intake < 10.9 mg/day, and increased with the increment of zinc intake (per mg/day: HR 1.14; 95% CI 1.11–1.16) in participants with zinc intake ≥ 10.9 mg/day. In conclusion, there was a J-shaped association between dietary zinc intake and new-onset hypertension in general Chinese adults, with an inflection point at about 10.9 mg/day.

关键词： dietary zinc intake     new-onset hypertension     general population     CHNS    

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Solution properties and self-association of multi-blocks like copolymer P(AM/AA) prepared by template

ZHANG Yuxi, WU Feipeng, LI Miaozhen, WANG Erjian

《化学科学与工程前沿（英文）》 2007年 第1卷 第1期   页码 68-71 doi: 10.1007/s11705-007-0014-8

摘要： The association and properties of multi-block like copolymers (TP) of acrylamide (AM) and acrylic acid (AA) prepared by template copolymerization in aqueous solution were studied. The results showed that the copolymers of this type exhibited a significant structure effect compared with that of similar random copolymers (CP) obtained by copolymerization in the absence of template. Decreasing the value of pH or adding Ca ion to the copolymer solution will make phase separation occur. The TEM images demonstrated that the phase separation caused by Ca ion was due to the formation of extensively intermolecular cross-linking. With the increase of the pH value of copolymer solution, the changes of the solution viscosity was similar with that of homopolyacrylic acid, which originally increased and then decreased. But the increase range of template copolymer was higher than that of homopolyacrylic acid. TEM images indicated that at the maximal viscosity the copolymer obtained in the presence of template formed coiled aggregates.

关键词： aqueous solution     homopolyacrylic     copolymer solution     significant structure     presence    

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Protein aggregation in association with delayed neuronal death in rat model of brain ischemia

GE Pengfei, FU Shuanglin, LI Wenchen, WANG Chonghao, ZHOU Chuibing, LUO Yinan, LUO Tianfei

《医学前沿（英文）》 2008年 第2卷 第1期   页码 70-74 doi: 10.1007/s11684-008-0013-2

摘要： To investigate the relationship between protein aggregation and delayed neuronal death, we adopted rat models of 20 min ischemia. Brain ischemia was produced using the 2-vessel occlusion (2VO) model in rats Light microscopy, transmission electronic microscopy and Western blot analysis were performed for morphological analysis of neurons, and protein detection. The results showed delayed neuronal death took place at 72 h after ischemia-reperfusion, protein aggregates formed at 4 h after reperfusion and reached the peak at 24 h after reperfusion, and Western blot analysis was consistent with transmission electronic microscopy. We conclude that protein aggregation is one of the important factors leading to delayed neuronal death.
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标题 作者 时间 类型 操作

Genome-wide association studies: inherent limitations and future challenges

null

期刊论文

Advancement in genetic variants conferring obesity susceptibility from genome-wide association studies

null

期刊论文

关联规则挖掘算法综述

毕建欣,张岐山

期刊论文

Obesity and overweight prevalence and its association with undiagnosed hypertension in Shanghai population

null

期刊论文

Genome-wide association study of the backfat thickness trait in two pig populations

Dandan ZHU,Xiaolei LIU,Rothschild MAX,Zhiwu ZHANG,Shuhong ZHAO,Bin FAN

期刊论文

How to judge the association of postmenopausal hormone therapy and the risk of breast cancer

Ling XU

期刊论文

Abiotic association of phthalic acid esters with humic acid of a sludge landfill

Xiaoli CHAI, Yongxia HAO, Xin ZHAO, Guixiang LIU, Ying ZHU, Rong JI, Jun WU, Huanhuan TONG, Youcai ZHAO

期刊论文

Distribution of antibiotic resistance genes and their association with bacteria and viruses in decentralized

期刊论文

A post-GWAS replication study confirming the association of

Shaohua YANG,Chao QI,Yan XIE,Xiaogang CUI,Yahui GAO,Jianping JIANG,Li JIANG,Shengli ZHANG,Qin ZHANG,Dongxiao SUN

期刊论文

Genome-wide association analysis reveals genetic loci and candidate genes associated with intramuscular

Xingwang WANG, Rongrong DING, Jianping QUAN, Linxue YANG, Ming YANG, Enqin ZHENG, Dewu LIU, Gengyuan CAI, Zhenfang WU, Jie YANG

期刊论文

Joint user association and resource partition for downlink-uplink decoupling in multi-tier HetNets

Zhi-yong FENG, Ze-bing FENG, T. Aaron GULLIVER

期刊论文

U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control

null

期刊论文

J-shaped association between dietary zinc intake and new-onset hypertension: a nationwide cohort study

期刊论文

Solution properties and self-association of multi-blocks like copolymer P(AM/AA) prepared by template

ZHANG Yuxi, WU Feipeng, LI Miaozhen, WANG Erjian

期刊论文

Protein aggregation in association with delayed neuronal death in rat model of brain ischemia

GE Pengfei, FU Shuanglin, LI Wenchen, WANG Chonghao, ZHOU Chuibing, LUO Yinan, LUO Tianfei

期刊论文