Biomedical subjects

Hong-Wen Deng

Publications and source records attributed to Hong-Wen Deng.

At least 19 recordsLinked to original sources

PubMed2026

ResSAT: enhancing spatial transcriptomics prediction from H&E-stained histology images with an interactive spot transformer.

Spatial transcriptomics has revolutionized RNA quantification with spatial resolution. Hematoxylin and eosin (H&E) images, the gold standard in medical diagnosis, offer insights into tissue structure, correlating with gene expression patterns. We introduce ResSAT (Residual networks with Spatial encoding-self-Attention Transformer), a framework for predicting spatially resolved transcriptomic profiles from H&E images by integrating image features, spatial locations, and self-attention transformer-based spot interactions. Benchmarking on 10 × Visium datasets, ResSAT outperforms existing methods and preserved biologically meaningful spatial patterns, promising reduced spatial transcriptomics profiling costs and rapid acquisition of numerous profiles.

Spatial Transcriptomics↗

PubMed2025

Phenotypic and Genetic Associations Between Cardiovascular Disease Subtypes and Alzheimer's Disease.

BACKGROUND: Cardiovascular disease (CVD) and Alzheimer's disease (AD) are major public health concerns that share overlapping risk factors and potential mechanistic pathways. While vascular contributions to cognitive decline are well-documented, the specific relationships between AD and different CVD subtypes remain poorly understood. METHODS: We examined associations between AD and 11 CVD subtypes using logistic regression models in two large biobanks: the UK Biobank (n = 502,133) and the All of Us Research Program (n = 287,011). Models were adjusted for demographic, lifestyle, and clinical covariates. We also explored genetic overlap between AD and CVD traits through colocalization of significant single nucleotide polymorphisms (SNPs) (p < 5×10-8) using genome-wide association study (GWAS) data. RESULTS: Most CVD subtypes were significantly associated with AD in both cohorts. Hypotension had the strongest and most consistent association, followed by hypertension and cerebral infarction. Acute myocardial infarction was the only subtype not significantly linked to AD. Genetic analyses revealed shared loci between AD and CVD-related traits, particularly in regions near APOE, MAPT, and genes influencing myocardial structure and vascular function. CONCLUSIONS: This study identifies subtype-specific CVD associations with AD across two diverse cohorts and highlights shared genetic architecture underlying heart-brain interactions. These findings underscore the importance of vascular health in AD risk and suggest that certain CVD subtypes, especially hypotension, may play underrecognized roles in cognitive decline.

Alzheimer’s disease↗

PubMed2007

Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass.

UNLABELLED: Several genome-wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta-analysis of genome-wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site-specific and sex-specific manner. INTRODUCTION: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome-wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta-analysis of genome-wide linkage scans in which femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied. MATERIALS AND METHODS: Data were accumulated from nine genome-wide scans involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD and by sex. For each study, genomic bins of 30 cM were defined and ranked according to the maximum LOD score they contained. While various densitometers were used in different studies, the ranking approach that we used means that the results are not confounded by the fact that different measurement devices were used. Significance for high average rank and heterogeneity was obtained through Monte Carlo testing. RESULTS: For LS-BMD, the quantitative trait locus (QTL) with greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this exhibited high heterogeneity and the effect was specific for women. Other significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12-q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3 (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33, 14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in average ranks of bins between men and women and the loci that regulated BMD in men and women and at different sites were largely distinct. CONCLUSIONS: This large-scale meta-analysis provided evidence for replication of several QTLs identified in previous studies and also identified a QTL on chromosome 18p11-q12.3, which had not been detected by individual studies. However, despite the large sample size, none of the individual loci identified reached genome-wide significance.

Bone Density↗

PubMed2006

A genome-wide linkage scan for quantitative trait loci underlying obesity related phenotypes in 434 Caucasian families.

To identify quantitative trait loci (QTLs) that contribute to obesity, we performed a large-scale whole genome linkage scan (WGS) involving 4,102 individuals from 434 Caucasian families. The most pronounced linkage evidence was found at the genomic region 20p11-12 for fat mass (LOD = 3.31) and percentage fat mass (PFM) (LOD = 2.92). We also identified several regions showing suggestive linkage signals (threshold LOD = 1.9) for obesity phenotypes, including 5q35, 8q13, 10p12, and 17q11.

Family↗

PubMed2006

Evaluating the correlation and prediction of trunk fat mass with five anthropometric indices in Chinese females aged 20-40 years.

BACKGROUND AND AIMS: Obesity is a worldwide problem, and excess trunk fat mass (FM(trunk)) has been associated with an increased risk of diseases. The early measurement of FM(trunk) has potential importance to evaluate trunk obesity. We sought to evaluate the correlation and predication of FM(trunk) with five anthropometric indices in Chinese females. METHODS AND RESULTS: A sample of 850 China females aged 20-40 years were recruited and divided into four age groups with a 5-year range in each group. Five anthropometric indices were measured or calculated. FM(trunk) in kg was measured using a dual-energy X-ray absorptiometry scanner. Principal component analysis (PCA) and multiple regression analysis were performed to develop prediction equations. There was an increasing trend of FM(trunk) and five anthropometric indices in successively older age groups. Four formed principal components (PCs) interpreted over 99% of the total variation of five relative anthropometric indices in all age groups. Regression analyses showed that four PCs combined explained a greater variance (R(2)=45.2-81.6%) in FM(trunk) than did each of the five indices alone (R(2)=2.4-72.2%). CONCLUSIONS: Our results suggested that there is an increasing trend of FM(trunk) and five anthropometric indices with aging; that age obviously influences the relationship of FM(trunk) and the anthropometric indices studied; and that the accuracy of predicting the FM(trunk) using five anthropometric indices combined is greater than using the five indices alone.

Absorptiometry, Photon↗

PubMed2006

Is a gene important for bone resorption a candidate for obesity? An association and linkage study on the RANK (receptor activator of nuclear factor-kappaB) gene in a large Caucasian sample.

In light of findings that osteoporosis and obesity may share some common genetic determination and previous reports that RANK (receptor activator of nuclear factor-kappaB) is expressed in skeletal muscles which are important for energy metabolism, we hypothesize that RANK, a gene essential for osteoclastogenesis, is also important for obesity. In order to test the hypothesis with solid data we first performed a linkage analysis around the RANK gene in 4,102 Caucasian subjects from 434 pedigrees, then we genotyped 19 SNPs in or around the RANK gene. A family-based association test (FBAT) was performed with both a quantitative measure of obesity [fat mass, lean mass, body mass index (BMI), and percentage fat mass (PFM)] and a dichotomously defined obesity phenotype-OB (OB if BMI > or = 30 kg/m(2)). In the linkage analysis, an empirical P = 0.004 was achieved at the location of the RANK gene for BMI. Family-based association analysis revealed significant associations of eight SNPs with at least one obesity-related phenotype (P < 0.05). Evidence of association was obtained at SNP10 (P = 0.002) and SNP16 (P = 0.001) with OB; SNP1 with fat mass (P = 0.003); SNP1 (P = 0.003) and SNP7 (P = 0.003) with lean mass; SNP1 (P = 0.002) and SNP7 (P = 0.002) with BMI; SNP1 (P = 0.003), SNP4 (P = 0.007), and SNP7 (P = 0.002) with PFM. In order to deal with the complex multiple testing issues, we performed FBAT multi-marker test (FBAT-MM) to evaluate the association between all the 18 SNPs and each obesity phenotype. The P value is 0.126 for OB, 0.033 for fat mass, 0.021 for lean mass, 0.016 for BMI, and 0.006 for PFM. The haplotype data analyses provide further association evidence. In conclusion, for the first time, our results suggest that RANK is a novel candidate for determination of obesity.

Adult↗

PubMed2006

Genetic determination and correlation of body weight and body mass index (BMI) and cross-sectional geometric parameters of the femoral neck.

INTRODUCTION: This study aimed to examine the genetic determination of body weight, body mass index (BMI) and cross-sectional geometric parameters of the femoral neck including cross-sectional area (CSA), cortical thickness (CT), sectional modulus (Z), and buckling ratio (BR), and to test the genetic correlation between body weight/BMI and the femoral neck geometric parameters. METHODS: A total of 929 healthy subjects from 292 Chinese nuclear families was included. Femoral neck geometric parameters were estimated from bone mineral density (BMD) and bone area which were measured by dual energy X-ray absorptiometry (DXA). RESULTS: The heritability (h(2)) estimate values were 0.643, 0.626, 0.626, 0.674, 0.405, and 0.615 for body weight, BMI, CSA, CT, Z, and BR, respectively. Body weight was significantly correlated with bone geometric parameters (p</=0.001) with genetic correlation (rho(G)) values of 0.551, 0.457, 0.571, and -0.385, and bivariate heritability (rho2G) values of 0.304, 0.209, 0.326, and 0.148 for CSA, CT, Z, and BR, respectively. Similar correlations (p</=0.001) were observed between BMI and bone geometric parameters, with rho(G) values of 0.446, 0.432, 0.334, and -0.362, and (rho2G) values of 0.199, 0.187, 0.112, and 0.131 for CSA, CT, Z, and BR, respectively. CONCLUSION: In summary, our study suggested that body weight, BMI, and femoral neck geometry were under strong genetic determination. The strong genetic correlations suggested that the genetic factors of bone geometry may be overlapped with those of body weight and BMI.

Absorptiometry, Photon↗

PubMed2006

HDC gene polymorphisms are associated with age at natural menopause in Caucasian women.

Histidine decarboxylase gene (HDC) encodes histidine decarboxylase which is the crucial enzyme for the biosynthesis of histidine. Studies have shown that histamine is likely to be involved in the regulation of reproduction system. To find the possible correlation between HDC gene and AANM (age at natural menopause), we selected 265 postmenopausal women from 131 nuclear families and performed a transmission disequilibrium test. Significant within-family associations with AANM for SNP rs854163 and SNP rs854158 of HDC gene were observed (P values=0.0018 and 0.0197, respectively). After 1000 permutations, SNP rs854163 still remained significant within-family association with AANM. Consistently, we also detected a significant within-family association between haplotype block 2 (defined by SNP rs854163 and rs860526) and AANM in the haplotype analyses (P value=0.0397). Our results suggest that the HDC gene polymorphisms are significantly associated with AANM in Caucasian women.

Age Factors↗

PubMed2006

Receiver-operating characteristic analyses of body mass index, waist circumference and waist-to-hip ratio for obesity: Screening in young adults in central south of China.

BACKGROUND & AIMS: Recent data suggest that current obesity diagnostic criterion based on body mass index (BMI) above 30 in Caucasians may not be appropriate for Asian populations. Our aim was to identify the usefulness of BMI, waist circumference (WC) and waist-to-hip ratio (WHR) in screening for obesity in an Asian population. METHODS: A cross-sectional sample of 1109 males and 879 females aged 20-45-yr were recruited. Height, weight, WC, hip circumference and percentage body fat (PBF) were measured in all subjects. Then receiver-operating characteristic analyses were used to evaluate the performances of the three anthropometric indices. RESULTS: BMI, WC and WHR showed strong positive correlation with PBF (r=0.47-0.75) in both males and females within both age groups. True-positive rates ranged from 82.4% to 94.1% and 68.8% to 86.3% in males and females, respectively. True-negative rates ranged from 64.1% to 84.7% and from 56.9% to 79.0%, respectively. The areas under the curves (AUCs) for WC and BMI were high (0.76-0.92) in both sexes and divided age groups (20-30-yr and 31-45-yr), and those for WHR were a little lower (0.74-0.88). CONCLUSIONS: BMI and WC are two important predictors for obesity in Chinese, and WHR is an alternative.

Adipose Tissue↗

PubMed2006

Genetic and environmental correlations between bone geometric parameters and body compositions.

The purpose of this study was to determine the genetic and environmental correlations between weight, lean mass and bone geometric parameters (sub-periosteal diameter, W; cross-sectional area, CSA; cortical thickness, CT; section modulus, Z; and buckling ratio, BR) of femoral neck. The sample was composed of 512 Caucasian pedigrees, including 2667 females and 1822 males. Bivariate quantitative genetic analyses were performed to evaluate the genetic (rho(G)), environmental (rho(E)) and phenotypic (rho(P)) correlations between the study traits. Univariate genetic analyses showed that the heritabilities (h(2)) for bone geometric parameters were significant (P < 0.001) ranging from 0.50 to 0.60. The significant common household effects indicated the common environment shared by household members for W, CSA, CT, Z and BR (P < 0.05), but the magnitude was small compared with heritabilities. rho(E), rho(G) and rho(P) between bone geometric parameters and weight, lean mass were generally significant. Interestingly, lean mass showed both stronger genetic and environmental correlations with the bone geometric parameters than weight. In addition, according to the magnitude of correlation coefficients, the rho(G) between body compositions and bone geometric parameters were generally stronger than rho(E) (except for that between BR and body compositions). These data suggested that the geometric parameters of femoral neck are under strong genetic control. Furthermore, some common genetic and environmental factors are shared by bone geometric parameters and weight, lean mass. The results may help understand the intertwined relationships between bone metabolisms, mechanical loading and body compositions.

Absorptiometry, Photon↗

PubMed2006

Epistasis between loci on chromosomes 2 and 6 influences human height.

CONTEXT: Human height is a typical and important complex trait, which is determined by both actions and interactions of multiple genes. Although an increasing number of genes or genomic regions have been discovered for their independent effects on height variation, no study has been performed to identify genes or loci that interact to control the trait. OBJECTIVE: This study aimed to search for potential genomic regions that harbor interactive genes underlying human height. METHODS: Here with a sample containing 3726 Caucasians, the largest one ever obtained from a single population of the same ethnicity among genetic linkage studies of human complex traits, we performed variance component linkage analyses of height based on a two-locus epistatic model. We examined pairwise genetic interaction among three regions, 9q22, 6p21, and 2q21, which achieved significant or suggestive linkage signals for height in our recent whole genome scan. RESULTS: Significant genetic interaction between 6p21 and 2q21 was detected, with 2q21 achieving a maximum LOD score of 3.21 (P = 0.0035) under the epistatic model, compared with a maximum LOD score of 1.63 under a two-locus additive model. Interestingly, 6p21 contains a cluster of candidate genes for skeletal growth, suggesting a mechanism whereby 2q21 regulates height through 6p21. CONCLUSION: By providing the first evidence for genetic interaction underlying human height variation, this study further delineated the genetic architecture of human height and contributed to the genetic dissection of human complex traits in general.

Adult↗

PubMed2006

Accurate haplotype inference for multiple linked single-nucleotide polymorphisms using sibship data.

Sibships are commonly used in genetic dissection of complex diseases, particularly for late-onset diseases. Haplotype-based association studies have been advocated as powerful tools for fine mapping and positional cloning of complex disease genes. Existing methods for haplotype inference using data from relatives were originally developed for pedigree data. In this study, we proposed a new statistical method for haplotype inference for multiple tightly linked single-nucleotide polymorphisms (SNPs), which is tailored for extensively accumulated sibship data. This new method was implemented via an expectation-maximization (EM) algorithm without the usual assumption of linkage equilibrium among markers. Our EM algorithm does not incur extra computational burden for haplotype inference using sibship data when compared with using unrelated parental data. Furthermore, its computational efficiency is not affected by increasing sibship size. We examined the robustness and statistical performance of our new method in simulated data created from an empirical haplotype data set of human growth hormone gene 1. The utility of our method was illustrated with an application to the analyses of haplotypes of three candidate genes for osteoporosis.

Algorithms↗

PubMed2006

Polymorphisms of estrogen-biosynthesis genes CYP17 and CYP19 may influence age at menarche: a genetic association study in Caucasian females.

Variation in age at menarche (AAM) is known to be substantially influenced by genetic factors, but the true causal genes remain largely unidentified. Because the increased amplitude of estrogen exposure of tissues initiates the onset of menarche, the genes involved in estrogen biosynthesis are natural candidate genes underlying AAM. Our study aimed to identify whether the CYP17 and CYP19, the two key genes involved in the biosynthesis of estrogen, are associated with AAM variation in 1048 females from 354 Caucasian nuclear families. We genotyped 38 SNPs and established the linkage disequilibrium blocks and haplotype structures that covered the full transcript length of those two genes. Family-based and population-based statistical analyses were used to test for associations with all of the single SNPs and haplotypes. Both methods consistently detected significant associations for five SNPs of CYP19 with AAM. Haplotype analyses corroborated our single-SNP results by showing that the haplotypes in block 1 were highly significant to AAM in population-based analyses. However, we could not find any association of CYP17 with AAM. Our study is the first to suggest the important effect of CYP19 on AAM variation in Caucasian females. It will be valuable to replicate and confirm these findings in other independent studies, aiming at eventually finding the hidden genetic mechanisms underlying the variation in AAM.

Adolescent↗

PubMed2006

Association analyses of CYP19 gene polymorphisms with height variation in a large sample of Caucasian nuclear families.

Human height is a complex trait regulated by multiple genetic and environmental factors. CYP19 (cytochrome P450 19) encodes aromatase, which catalyses the rate-limiting step in the conversion of androgens to estrogens. Deleterious mutations in CYP19 can result in estrogen deficiency that will influence adult height to certain extent. In the present study, we aimed to test the associations between the CYP19 gene polymorphisms with adult height variation, using family-based association methods, such as QTDT (quantitative transmission disequilibrium test) and FBAT (family-based association test) in 1,873 subjects from 405 Caucasian nuclear families. We found one SNP (rs730154) significantly associated with height by both QTDT (P=0.0030) and FBAT (P=0.0016) analyses. Haplotype analyses corroborated our single-marker results by showing that the haplotypes in block 4 containing rs730154 were significantly associated with height variation. We thus concluded that CYP19 could be one of the genetic factors influencing adult height in Caucasians. Further studies are required to identify the causal functional variants responsible for Caucasian height within the CYP19 gene.

Adult↗

PubMed2006

Genetic linkage of human height is confirmed to 9q22 and Xq24.

Human height is an important and heritable trait. Our previous two genome-wide linkage studies using 630 (WG1 study) and an extended sample of 1,816 Caucasians (WG2 study) identified 9q22 [maximum LOD score (MLS)=2.74 in the WG2 study] and preliminarily confirmed Xq24 (two-point LOD score=1.91 in the WG1 study, 2.64 in the WG2 study) linked to height. Here, with a much further extended large sample containing 3,726 Caucasians, we performed a new genome-wide linkage scan and confirmed, in high significance, the two regions' linkage to height. An MLS of 4.34 was detected on 9q22 and a two-point LOD score of 5.63 was attained for Xq24. In an independent sub-sample (i.e., the subjects not involved in the WG1 and WG2 studies), the two regions also achieved significant empirical P values (0.002 and 0.004, respectively) for "region-wise" linkage confirmation. Importantly, the two regions were replicated on a genotyping platform different from the WG1 and WG2 studies (i.e., a different set of markers and different genotyping instruments). Interestingly, 9q22 harbors the ROR2 gene, which is required for growth plate development, and Xq24 was linked to short stature. With the largest sample from a single population of the same ethnicity in the field of linkage studies for complex traits, our current study, together with two previous ones, provided overwhelming evidence substantiating 9q22 and Xq24 for height variation. In particular, our three consecutive whole genome studies are uniquely valuable as they represent the first practical (rather than simulated) example of how significant increase in sample size may improve linkage detection for human complex traits.

Adult↗

PubMed2006

Genomewide linkage scan for quantitative trait loci underlying variation in age at menarche.

CONTEXT: Age at menarche (AAM) is an important anthropological variable that has major implications for a woman's health later in life. Genetic influence has been shown to contribute greatly to AAM, but the specific genetic determinants are largely unknown. OBJECTIVE: The objective of this study was to identify the quantitative trait loci (QTL) underlying the variations in AAM. METHODS: We performed a large-scale, genomewide, linkage scan in 2461 Caucasian women from 402 pedigrees. All subjects were genotyped with 410 microsatellite markers spaced approximately 8.9 cM apart across the human genome. Using the variance component method, we conducted multipoint linkage analyses and two-locus tests for epistatic interaction. RESULTS: The strongest linkage signal was obtained at the genomic region of 22q13 (LOD, 3.70); the other two suggestive linkages were on 22q11 (LOD, 2.68) and 11q23 (LOD, 1.98), respectively. We also detected significant epistatic interaction between genomic regions 22q13 and 3q13. CONCLUSIONS: The identification of QTL and epistatic interaction in a large female sample laid a foundation for independent replication and fine-mapping studies as well as positional and functional candidate gene studies aimed at finding the causal genetic variants and hidden mechanisms concerning the variations in AAM.

Age Factors↗

PubMed2006

Paternal uniparental isodisomy of the entire chromosome 3 revealed in a person with no apparent phenotypic disorders.

Uniparental disomy (UPD) is a rare genetic abnormality. During a whole genome linkage study we identified a case of paternal uniparental isodisomy 3 serendipitously. This is the first ascertained human paternal UPD for chromosome 3 (UPD3pat). The finding of this paternal UPD case of the entire chromosome 3 with no apparent phenotypic disorders suggests that there are no paternal imprinted genes causing rare genetic disorders on chromosome 3.

Alleles↗

PubMed2006

Tests of linkage and association of PTH/PTHrP receptor type 1 gene with bone mineral density and height in Caucasians.

Parathyroid hormone/parathyroid hormone-related peptide receptor type 1 (PTHR1) plays an important role in calcium metabolism. It was previously shown to influence variation in bone mineral density (BMD). To investigate its importance in a typical U.S. Caucasian population, we tested linkage or association of the PTHR1 gene with BMD and height. Altogether, 1873 subjects from 405 Caucasian nuclear families were studied. BMD was measured at the lumbar spine (L1-L4) and total hip (femoral neck, trochanter, and intertrochanter regions). Four single nucleotide polymorphisms (SNPs) in the PTHR1 gene were genotyped. Sixteen haplotypes were reconstructed. Only two major haplotypes had frequencies >3% and were thus used for the analysis. Analyses were performed for BMD and height in the total sample and for peak BMD (PBMD) achieved in offspring subjects aged 20-50 in a subsample of 387 nuclear families. We found suggestive evidence for total association between haplotype 13 (AATG) and hip PBMD (P = 0.031). For height, evidence of within-family association was suggested for SNP1, SNP2, and haplotype 4 (GGCA) (P < or = 0.05). Our findings suggest that the PTHR1 gene may be important for PBMD, height variation, or both, although the significance is dampened by correction for multiple testing.

Absorptiometry, Photon↗