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Kui Zhang

Publications and source records attributed to Kui Zhang.

9 recordsLinked to original sources
PubMed2026

A genome-wide cross-trait analysis characterizes the shared genetic architecture between rheumatoid arthritis and psychiatric disorders.

OBJECTIVES: Patients with RA have a 2- to 3-fold elevated risk of psychiatric disorders, suggesting an underlying genetic link between these phenotypes. However, the shared genetic architectures and pathological mechanisms driving RA-psychiatric disorder comorbidity remain to be fully elucidated. Herein, we performed cross-trait analysis to investigate the shared genetic architecture between RA and psychiatric disorders. METHODS: Leveraging European-ancestry genome-wide association studies (GWASs) datasets of RA (n = 1 026 690) and 10 major psychiatric disorders (n = 14 307-1 222 882), we performed cross-trait pleiotropic analysis to identify the shared pleiotropic loci and genes between RA and psychiatric disorders, followed by functional annotation and Mendelian randomization analysis to explore the pathological mechanisms underlying RA-psychiatric disorder comorbidity. RESULTS: Our analysis revealed significant positive genetic correlations between RA and seven psychiatric disorders, such as major depressive disorder. From these correlations, we identified 61 pleiotropic loci jointly influencing RA and psychiatric disorder risk, along with 208 pleiotropic genes predominantly involved in immune and inflammatory response biological processes. Druggable target exploration identified 21 drug-gene interactions involving pleiotropic genes, with two genes (RHOA and TRAF3) classified in the clinically actionable category, representing potential therapeutic targets for both RA and psychiatric disorders. Mendelian randomization further demonstrated a bidirectional causal relationship between RA and schizophrenia, while supporting the causal roles of attention-deficit/hyperactivity disorder, major depressive disorder and post-traumatic stress disorder in increasing RA risk. CONCLUSION: Our findings elucidate the shared genetic architecture between RA and psychiatric disorders, providing novel insights into the pathological mechanisms underlying their comorbidity and laying the groundwork for improved comorbidity management.

Arthritis, Rheumatoid↗
PubMed2003

[Role of leptin in the pathogenesis of obesity-related hypertension].

OBJECTIVE: To assess the role of leptin in the pathogenesis of obesity-related hypertension and the relationship between blood pressure (BP), and body mass index (BMI), insulin resistance and leptin were examined. METHODS: 560 non-diabetic men, aged 35 - 75, selected from volunteers of health screening test during 2 000 were divided into hypertension group (n = 321, BP >or= 140/90 mm Hg without antihypertensive medication). and normal blood pressure group (n = 239). The body weight, waist hip ratio,BP, plasma glucose, serum lipids, true insulin (TI) and leptin were measured after overnight fast. Insulin sensitivity was assessed by the HOMA insulin resistance index (HOMA-R). RESULTS: Fasting leptin level showed good correlation with BMI, fasting TI, HOMA-R, BP and also triglycerides (all P < 0.01). After adjustment for age, BMI and HOMA-R, serum leptin was still positively correlated to SBP (r = 0.11, P < 0.05), and was significantly higher in hypertensive subjects than in normotensive subjects (geometric mean 6.4 vs 4.7 micro g/L, P < 0.001). Logistic regression analysis demonstrated that leptin remained significantly associated with hypertension after adjustment for potentially confounding factors. CONCLUSION: Leptin may play an important role in the pathogenesis of obesity related hypertension.

Adult↗
PubMed2003

Haplotype block partition with limited resources and applications to human chromosome 21 haplotype data.

Recent studies have shown that the human genome has a haplotype block structure such that it can be decomposed into large blocks with high linkage disequilibrium (LD) and relatively limited haplotype diversity, separated by short regions of low LD. One of the practical implications of this observation is that only a small fraction of all the single-nucleotide polymorphisms (SNPs) (referred as "tag SNPs") can be chosen for mapping genes responsible for human complex diseases, which can significantly reduce genotyping effort, without much loss of power. Algorithms have been developed to partition haplotypes into blocks with the minimum number of tag SNPs for an entire chromosome. In practice, investigators may have limited resources, and only a certain number of SNPs can be genotyped. In the present article, we first formulate this problem as finding a block partition with a fixed number of tag SNPs that can cover the maximal percentage of the whole genome, and we then develop two dynamic programming algorithms to solve this problem. The algorithms are sufficiently flexible to permit knowledge of functional polymorphisms to be considered. We apply the algorithms to a data set of SNPs on human chromosome 21, combining the information of coding and noncoding regions. We study the density of SNPs in intergenic regions, introns, and exons, and we find that the SNP density in intergenic regions is similar to that in introns and is higher than that in exons, results that are consistent with previous studies. We also calculate the distribution of block break points in intergenic regions, genes, exons, and coding regions and do not find any significant differences.

Chromosomes, Human, Pair 21↗
PubMed2002

Haplotype block structure and its applications to association studies: power and study designs.

Recent studies have shown that the human genome has a haplotype block structure, such that it can be divided into discrete blocks of limited haplotype diversity. In each block, a small fraction of single-nucleotide polymorphisms (SNPs), referred to as "tag SNPs," can be used to distinguish a large fraction of the haplotypes. These tag SNPs can potentially be extremely useful for association studies, in that it may not be necessary to genotype all SNPs; however, this depends on how much power is lost. Here we develop a simulation study to quantitatively assess the power loss for a variety of study designs, including case-control designs and case-parental control designs. First, a number of data sets containing case-parental or case-control samples are generated on the basis of a disease model. Second, a small fraction of case and control individuals in each data set are genotyped at all the loci, and a dynamic programming algorithm is used to determine the haplotype blocks and the tag SNPs based on the genotypes of the sampled individuals. Third, the statistical power of tests was evaluated on the basis of three kinds of data: (1) all of the SNPs and the corresponding haplotypes, (2) the tag SNPs and the corresponding haplotypes, and (3) the same number of randomly chosen SNPs as the number of tag SNPs and the corresponding haplotypes. We study the power of different association tests with a variety of disease models and block-partitioning criteria. Our study indicates that the genotyping efforts can be significantly reduced by the tag SNPs, without much loss of power. Depending on the specific haplotype block-partitioning algorithm and the disease model, when the identified tag SNPs are only 25% of all the SNPs, the power is reduced by only 4%, on average, compared with a power loss of approximately 12% when the same number of randomly chosen SNPs is used in a two-locus haplotype analysis. When the identified tag SNPs are approximately 14% of all the SNPs, the power is reduced by approximately 9%, compared with a power loss of approximately 21% when the same number of randomly chosen SNPs is used in a two-locus haplotype analysis. Our study also indicates that haplotype-based analysis can be much more powerful than marker-by-marker analysis.

Algorithms↗
PubMed2002

A dynamic programming algorithm for haplotype block partitioning.

We develop a dynamic programming algorithm for haplotype block partitioning to minimize the number of representative single nucleotide polymorphisms (SNPs) required to account for most of the common haplotypes in each block. Any measure of haplotype quality can be used in the algorithm and of course the measure should depend on the specific application. The dynamic programming algorithm is applied to analyze the chromosome 21 haplotype data of Patil et al. [Patil, N., Berno, A. J., Hinds, D. A., Barrett, W. A., Doshi, J. M., Hacker, C. R., Kautzer, C. R., Lee, D. H., Marjoribanks, C., McDonough, D. P., et al. (2001) Science 294, 1719-1723], who searched for blocks of limited haplotype diversity. Using the same criteria as in Patil et al., we identify a total of 3,582 representative SNPs and 2,575 blocks that are 21.5% and 37.7% smaller, respectively, than those identified using a greedy algorithm of Patil et al. We also apply the dynamic programming algorithm to the same data set based on haplotype diversity. A total of 3,982 representative SNPs and 1,884 blocks are identified to account for 95% of the haplotype diversity in each block.

Algorithms↗
PubMed2002

On a family-based haplotype pattern mining method for linkage disequilibrium mapping.

Linkage disequilibrium mapping is an important tool in disease gene mapping. Recently, Toivonen et al. [1] introduced a haplotype mining (HPM) method that is applicable to data consisting of unrelated high-risk and normal haplotypes. The HPM method orders haplotypes by their strength of association with trait values, and uses all haplotypes exceeding a given threshold of strength of association to predict the gene location. In this study, we extend the HPM method to pedigree data by measuring the strength of association between a haplotype and quantitative traits of interest using the Quantitative Pedigree Disequilibrium Test proposed by Zhang et al. [2]. This family-based HPM (F-HPM) method can incorporate haplotype information across a set of markers and allow both missing marker data and ambiguous haplotype information. We use a simulation procedure to evaluate the statistical significance of the patterns identified from the F-HPM method. When the F-HPM method is applied to analyze the sequence data from the seven candidate genes in the simulated data sets in the 12th Genetic Analysis Workshop, the association between genes and traits can be detected with high power, and the estimated locations of the trait loci are close to the true sites.

Chromosome Mapping↗
PubMed2002

[The relationship between serum leptin, proinsulin, true insulin levels and insulin resistance in non-diabetic subjects: a population-based study].

OBJECTIVE: Leptin is involved in the regulation of body weight and metabolism. Previous data have suggested that leptin levels are related to insulin resistance and in a few reports with impaired insulin secretion. Some even revealed the existence of adipoinsular axis. However, little is known of these relations in Chinese population. With the availability of measurements of true insulin (TI), proinsulin (PI) and leptin, we examined the possible correlation of leptin with TI, PI and with insulin resistance (the HOMA model) in non-diabetic subjects of north China. We also evaluated whether leptin levels were associated with impaired insulin secretion, as evaluated by the fasting PI/TI ratio. METHODS: 902 non-diabetic subjects (670 with normal and 232 impaired glucose tolerance, aged 30 - 80 y) from a population of Beijing residents who underwent a diabetes survey in 2000 were studied. Fasting serum leptin, PI and TI levels were detected by sensitive and specific enzyme-linked immunosorbent assays (ELISA) which were all developed in our laboratory. RESULTS: Serum leptin values were higher in women. Correlation analysis showed that leptin levels were significantly correlated with fasting TI, PI and insulin resistance (HOMA-IR) (in men, n = 794, r = 0.345, 0.236 and 0.364 respectively; in women, n = 110, r = 0.574, 0.375 and 0.576 respectively, P < 0.001), but not with PI/TI ratio (r = -0.09, P < 0.01) in both sex. After adjustment for age, body mass index (BMI) and waist-to-hip ratio (WHR), leptin levels remained significantly correlated with TI, PI and HOMA-IR, although the magnitude of the association was considerably attenuated. CONCLUSIONS: TI and PI levels were positively related to leptin levels independent of obesity and body fat distribution. Thus, subjects with increased insulin levels and/or insulin resistance may be relatively resistant to the effects of leptin, suggesting a dysfunction of leptin-insulin axis. However, leptin levels are not significantly associated with the fasting PI/TI ratio suggesting that leptin levels are not associated with an impairment in insulin secretion. The role of association between hyperinsulinemia/insulin resistance and hyperleptinemia/leptin resistance in the pathogenesis of insulin resistance-related diseases needs further study.

Adult↗
PubMed2002

[Management of extensive closed internal degloving injury].

OBJECTIVE: To study the management of extensive closed internal degloving injury (CIDI). METHODS: From September 1987 to October 1999, 18 cases of CIDI were retrospectively reviewed. Of 18 cases, there were 7 cases in thigh, 6 cases in legs and 5 cases in pelvis, ranging from 15 cm x 12 cm to 38 cm x 25 cm in size. Various managements were adopted according to the severity of the injury, including vacuum drainage and adjuvant compression in 5 cases, regrafting of defatting fenestrated full-thickness skin by non-resection in 8 cases, and skin grafting with transfer of myocutaneous flap in 5 cases. Among them, there were 11 cases of bone and articular fixation or repair, 4 cases of principal vessels repair. All of the cases were evaluated clinically and followed up for 6 months to 3 years. RESULTS: In the 8 cases repaired by regrafting of defatting fenestrated full-thickness skin, only one case of skin necrosis, 5 cm x 2 cm in size, recovered after skin grafting; the others healed well. All of the patients recovered normal life and had normal limbs. CONCLUSION: It's crucial to make a careful assessment about the injury severity of CIDI, to stress on importance of management of both CIDI and deep injury, and to choose proper options after comprehensive assessment of the injury.

Adolescent↗