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Qing-Yang Huang

Publications and source records attributed to Qing-Yang Huang.

18 recordsLinked to original sources
PubMed2006

Identification of two sex-specific quantitative trait loci in chromosome 11q for hip bone mineral density in Chinese.

BACKGROUND: Chromosome 11q has not only been found to contain mutations responsible for the several Mendelian disorders of the skeleton, but it has also been linked to bone mineral density (BMD) variation in several genome-wide linkage studies. Furthermore, quantitative trait loci (QTL) affecting BMD in inbred mice and baboons have been mapped to a region syntenic to human chromosome 11q. The aim of the present study is to determine whether there is a QTL for BMD variation on chromosome 11q in the Chinese population. METHODS: Nineteen microsatellite markers were genotyped for a 75 cM region on 11q13-25 in 306 Chinese families with 1,459 subjects. BMD (g/cm(2)) was measured by DXA. Linkage analyses were performed using the variance component linkage analysis method implemented in Merlin software. RESULTS: For women, a maximum LOD score of 1.62 was achieved at 90.8 cM on 11q21 near the marker D11S4175 for femoral neck BMD; LOD scores greater than 1.0 were observed on 11q13 for trochanter BMD. For men, a maximum LOD score of 1.57 was achieved at 135.8 cM on 11q24 near the marker D11S4126 for total hip BMD. CONCLUSION: We have not only replicated the previous linkage finding on chromosome 11q but also identified two sex-specific QTL that contribute to BMD variation in Chinese women and men.

Bone Density↗
PubMed2006

Confirmation of linkage to chromosome 1q for spine bone mineral density in southern Chinese.

Chromosome 1q has previously been linked to bone mineral density (BMD) variation in the general population in several genome-wide linkage studies in both humans and mouse model. The aim of present study is to replicate and fine map the QTL influencing BMD in chromosome 1q in southern Chinese. Twelve microsatellite markers were genotyped for a 57 cMu region in the chromosome 1q in 306 southern Chinese families with 1,459 subjects. Each of these families was ascertained through a proband with BMD Z-scores less than -1.3 at the hip or spine. BMD (g/cm2) at the L1-4 lumbar spine, femoral neck (FN), trochanter and total hip was measured by dual-energy X-ray absortiometry. Linkage analyses were performed using the variance component linkage analysis method implemented in Merlin software. Four markers (D1S2878, D1S196, D1S452, and D1S218) achieved a LOD score greater than 1.0 with spine BMD, with the maximum multipoint LOD score of 2.36 at the marker D1S196. We did not detect a LOD score greater than 1.0 for BMD at the FN, trochanter, or total hip in multipoint linkage analyses. Our results present the first evidence for the presence of an osteoporosis susceptibility gene on chromosome 1q in non-Caucasian subjects. Further analyses of candidate genes are warranted to identify QTL genes and variants underlying the variations of BMD in this region.

Adult↗
PubMed2006

Genetics of osteoporosis.

Osteoporosis is a common disease with a strong genetic component. In recent years, some progress has been made in understanding the genetic basis of osteoporosis. Genetic factors contribute to osteoporosis by influencing not only bone mineral density but also bone size, bone quality, and bone turnover. Meta-analysis has been used to define the role of several candidate genes in osteoporosis. Some quantitative trait loci that regulate bone mass identified by linkage studies in humans and experimental animals have been replicated in multiple populations. Genes that cause monogenic bone diseases also contribute to regulation of bone mass in the normal population. Genome-wide association studies and functional genomics approaches have recently begun to apply to genetic studies of osteoporosis. In the future, not only single gene but also the entire gene networks involved in osteoporosis and regulation of bone mass will systematically be discovered through integrative genomics.

Animals↗
PubMed2006

CA repeat polymorphism of the TNFR2 gene is not associated with bone mineral density in two independent Caucasian populations.

Osteoporosis has a strong genetic component, but the genes involved are poorly defined. Genome-wide scans in multiple populations have identified chromosome 1p36 as one region linked to bone mineral density (BMD). The tumor necrosis factor receptor 2 (TNFR2) at 1p36 is a positional and functional candidate gene in osteoporosis. In this study, we conducted linkage and association tests between the CA repeat polymorphism of the TNFR2 gene and BMD in two large independent samples using the quantitative transmission disequilibrium test (QTDT) program. The first group of subjects was composed of 1836 individuals from 79 multigeneration pedigrees. The second group was a randomly ascertained set of 636 individuals from 157 nuclear families. We found no evidence of association or linkage for spine or hip BMD in the samples of the multigenerational pedigrees or nuclear families. Through testing for association and for linkage, our data do not support the TNFR2 gene as a QTL underlying hip or spine BMD variation in our Caucasian populations.

Adult↗
PubMed2006

Linkage and association studies of the susceptibility genes for type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is a complex disease characterized by hyperglycemia, insulin resistance, and impaired insulin secretion. T2DM is under strong genetic control. Identification and characterization of genes involved in determining T2DM will contribute to a greater understanding of the pathogenesis of T2DM, and ultimately might lead to the development of better diagnosis, prevention and treatment strategies. Efforts to identify T2DM susceptibility genes have focused on candidate gene approach (association studies) and genome-wide scans (linkage analyses). In this article, we review the current status for mapping and identification of genes for T2DM, with a focus on some promising regions (or genes) and future prospects.

Association↗
PubMed2006

Linkage and association between CA repeat polymorphism of the TNFR2 gene and obesity phenotypes in two independent Caucasian populations.

Previously, our group has reported a suggestive linkage evidence of 1p36 with body mass index (BMI) (LOD = 2.09). The tumor necrosis factor receptor 2 (TNFR2) at 1p36 is an excellent positional and functional candidate gene for obesity. In this study, we have investigated the linkage and association between the TNFR2 gene and obesity phenotypes in two large independent samples, using the quantitative transmission disequilibrium tests (QTDT). The first group was made up of 1,836 individuals from 79 multi-generation pedigrees. The second group was a randomly ascertained set of 636 individuals from 157 US Caucasian nuclear families. Obesity phenotypes tested include BMI, fat mass, and percentage fat mass (PFM). A significant result (P = 0.0056) was observed for linkage with BMI in the sample of the multigenerational pedigrees. Our data support the TNFR2 gene as a quantitative trait locus (QTL) underlying BMI variation in the Caucasian populations.

Adult↗
PubMed2006

[PPARgamma variants and complex diseases].

Peroxisome proliferator-activated receptor gamma is a member of the nuclear hormone receptor superfamily. Mainly expressed in adipose tissue, PPARgamma promotes the differentiation of adipocytes and modulates the expression of many genes involved in the synthesis of adipocytokines in the adipose tissue. It is also the target molecule of the thiazolidinediones. Polymorphisms of the PPARgamma gene may influence pancreatic beta-cell function and result in changes in insulin secretion and insulin sensitivity of the peripheral tissues. They are also associated with risks of type 2 diabetes, obesity, cardiovascular diseases and cancer. Elucidation of its mechanism could be of major importance to the diagnosis, prevention and treatment of complex diseases.

Animals↗
PubMed2004

Genome scan for QTLs underlying bone size variation at 10 refined skeletal sites: genetic heterogeneity and the significance of phenotype refinement.

To identify quantitative trait loci (QTLs) underlying variation in bone size, we conducted a whole-genome linkage scan in 53 pedigrees with 630 subjects using 380 microsatellite markers. Lumbar area 1, 2, 3, and 4 at the spine, femoral neck, trochanter, intertrochanter areas at the hip, ultradistal, mid-distal, and one-third distal areas at the wrist were measured by dual-energy X-ray absorptiometry (DXA), and adjusted for age, height, weight, and sex. Two-point and multipoint linkage analyses were performed for skeletal bone size at each site and their composite measurements using the SOLAR package. Two chromosomal regions (1q22 and 10q21) were identified with significant evidence of linkage (LOD > 4.32) to one-third distal area, and three were identified with suggestive evidence of linkage (LOD > 2.93) to bone size in one skeletal site. Our results indicated that the low power of QTLs mapping for composite phenotypic measurements may result from genetic heterogeneity of complex traits.

Bone and Bones↗
PubMed2004

A follow-up linkage study for bone size variation in an extended sample.

Bone size, which has strong genetic determination, is an important determinant of bone strength and a risk factor of osteoporotic fractures. We previously reported an approximately 10-cm genome-wide linkage scan in 630 subjects from 53 US Caucasian pedigrees. The strongest evidence of linkage was obtained on chromosome 17q22 near the marker D17S787, with a two-point LOD score of 3.98 and a multipoint maximum LOD score (MLS) of 3.01. Additionally, suggestive linkages (1.54 < MLS < 2.83) were found at the other four chromosomal regions. In the present study, with an attempt to further examine our previous findings, we perform a follow-up linkage analysis in an expanded sample of 79 pedigrees with 1816 subjects. The total sample contains >80,000 informative relative pairs for linkage analyses, including 3846 sib pairs. Fifteen markers covering the above five promising regions are genotyped, narrowing the average genomic distance from approximately 10 to 5 cm. In the total 79 pedigrees, support of linkage was achieved for the wrist bone size at 17q22 with a two-point LOD score of 2.27 (P = 0.0006) and MLS of 1.78 (P = 0.002). The genomic region 17q22 includes COL1A1, a strong candidate gene that is significantly associated with osteoporotic fracture risk. Our data suggest that this region is promising for further exploratory studies.

Adult↗
PubMed2004

A follow-up linkage study for quantitative trait loci contributing to obesity-related phenotypes.

We have recently reported a whole-genome scan in a sample of 630 subjects from 53 extended pedigrees, in which several genomic regions that may contain quantitative trait loci (QTLs) for obesity were suggested. In the present study, with an attempt to confirm our previous findings, we performed a follow-up linkage study in an expanded sample of 79 pedigrees with 1816 subjects (including expanded previous 53 pedigrees and 26 newly recruited pedigrees containing 1058 subjects). A new set of microsatellite markers spanning previously identified regions were selected, with the average genomic distance narrowed from approximately 10 cM to approximately 5 cM in this study. Using a variance component method, we performed two- and multipoint linkage analyses in the following three sample sets: expanded previous 53 pedigrees (758 subjects), 26 new pedigrees, and 79 total pedigrees. For body mass index, analyses of the expanded 53 pedigrees attained a LOD score of 2.32 near marker D1S468 in two-point analysis and a maximum LOD score (MLS) of 2.21 in multipoint analysis; 2q14 near marker D2S347 attained a LOD score of 3.42 in two-point analysis and a MLS of 3.93 in multipoint analysis. The linkage peaks at 1p36 and 2q14 were further supported in the analyses of all 79 pedigrees, with multipoint MLS being 1.38 and 0.90, respectively. For fat mass, genomic region 6q27 achieved a LOD score of 1.24 in two-point analysis and an MLS of 0.92 in multipoint analysis in all 79 pedigrees. Our data support that 1p36, 2q14, and 6q27 are promising regions that may harbor QTLs for obesity phenotypes.

Adult↗
PubMed2003

Searching for osteoporosis genes in the post-genome era: progress and challenges.

Osteoporosis is a common skeletal disease characterized by low bone mineral density (BMD), deterioration of bone microarchitecture and increased fracture risk. It is a complex disease that has high social and economic costs. Osteoporosis and its associated phenotypes are under the strong genetic control. Identification and characterization of specific loci or genes involved in determining osteoporosis and its associated phenotypes will contribute to a greater understanding of the pathogenesis of osteoporosis, and ultimately might lead to the development of better diagnosis, prevention and treatment strategies. Efforts to identify osteoporosis genes have focused on three approaches: animal models, candidate gene approach, and genome-wide scans. In this article, we review the current status for mapping and identification of genes for osteoporosis, with a focus on some promising regions and future prospects.

Animals↗
PubMed2003

Linkage and association of the CA repeat polymorphism of the IL6 gene, obesity-related phenotypes, and bone mineral density (BMD) in two independent Caucasian populations.

Genetic factors play an important role in osteoporosis and obesity, two serious public health problems in the world. We investigated the relationships between obesity-related phenotypes, bone mineral density (BMD) and the CA repeat polymorphism of the IL6 gene in two large independent samples using the quantitative transmission disequilibrium test (QTDT). The first sample consisted of 1,816 individuals from 79 multigenerational pedigrees. Each pedigree was identified through a proband with BMD Z-scores </=-1.28 at the hip or spine. The second sample was a randomly ascertained set of 636 individuals from 157 nuclear families. Ten alleles containing 9-18 CA repeats were identified in our Caucasian populations. For body mass index (BMI), fat mass and percentage fat mass (PFM), highly significant (P<0.01) or significant (P<0.05) results were found for linkage in our sample of nuclear families and for association in the multigenerational pedigrees. We also observed weak evidence for linkage (P=0.069) with spine BMD and for association with hip BMD in the sample of multigenerational pedigrees. Our results suggest that genetic variation in or near the IL6 locus may be involved in the etiology of obesity and osteoporosis.

Adult↗
PubMed2003

Several genomic regions potentially containing QTLs for bone size variation were identified in a whole-genome linkage scan.

Bone size is an important determinant of osteoporotic fractures. For a sample of 53 pedigrees that contains more than 10,000 relative pairs informative for linkage analyses, we performed a whole-genome linkage scan using 380 microsatellite markers to identify genomic regions that may contain QTLs of bone size (two dimensional measurement by dual energy X-ray absorptiometry). We conducted two- and multi-point linkage analyses. Several potentially important genomic regions were identified. For example, the genomic region 17q23 may contain a QTL for wrist (ultra distal) bone size variation; a LOD score of 3.98 is achieved at D17S787 in two-point analyses and a maximum LOD score (MLS) of 3.01 is achieved in multi-point analyses in 17q23. 19p13 may contain a QTL for hip bone size variation; a LOD score of 1.99 is achieved at D19S226 in two-point analyses and a MLS of 2.83 is achieved in 19p13 in multi-point analyses. The genomic region identified on chromosome 17 for wrist bone size seems to be consistent with that identified for femur head width variation in an earlier whole-genome scan study. The genomic regions identified in this study and an earlier investigation on one-dimensional bone size measurement by radiography are compared. The two studies may form a basis for further exploration with larger samples and/or denser markers for confirmation and fine mapping studies to eventually identify major functional genes and the associated etiology for osteoporosis.

Age Factors↗
PubMed2002

A whole-genome linkage scan suggests several genomic regions potentially containing QTLs underlying the variation of stature.

Human height is a complex trait under the control of both genetic and environment factors. In order to identify genomic regions underlying the variation of stature, we performed a whole-genome linkage analysis on a sample of 53 human pedigrees containing 1,249 sib pairs, 1,098 grandparent-grandchildren pairs, 1,993 avuncular pairs, and 1,172 first-cousin pairs. Several genomic regions were suggested by our study to be linked with human height variation. These regions include 5q31 at 144 cM from pter on chromosome 5 (with a maximum LOD score of 2.14 in multipoint linkage analyses), Xp22 at the marker DXS1060, and Xq25 at DXS1001 on the X chromosome (with LOD scores of 1.95 and 1.91, respectively, in two-point linkage analyses). Noticeably, Xp22 happens to be the very region where a newly identified gene underlying idiopathic short stature, SHOX, maps. Based on our findings, further confirmation and fine-mapping studies are to be pursued on expanded samples and/or with denser markers for eventual identification of major functional genes involved in human height variation.

Body Height↗
PubMed2002

A genomewide linkage scan for quantitative-trait loci for obesity phenotypes.

Obesity is an increasingly serious health problem in the world. Body mass index (BMI), percentage fat mass, and body fat mass are important indices of obesity. For a sample of pedigrees that contains >10,000 relative pairs (including 1,249 sib pairs) that are useful for linkage analyses, we performed a whole-genome linkage scan, using 380 microsatellite markers to identify genomic regions that may contain quantitative-trait loci (QTLs) for obesity. Each pedigree was ascertained through a proband who has extremely low bone mass, which translates into a low BMI. A major QTL for BMI was identified on 2q14 near the marker D2S347 with a LOD score of 4.04 in two-point analysis and a maximum LOD score (MLS) of 4.44 in multipoint analysis. The genomic region near 2q14 also achieved an MLS >2.0 for percentage of fat mass and body fat mass. For the putative QTL on 2q14, as much as 28.2% of BMI variation (after adjustment for age and sex) may be attributable to this locus. In addition, several other genomic regions that may contain obesity-related QTLs are suggested. For example, 1p36 near the marker D1S468 may contain a QTL for BMI variation, with a LOD score of 2.75 in two-point analysis and an MLS of 2.09 in multipoint analysis. The genomic regions identified in this and earlier reports are compared for further exploration in extension studies that use larger samples and/or denser markers for confirmation and fine-mapping studies, to eventually identify major functional genes involved in obesity.

Adipose Tissue↗
PubMed2002

Mutation patterns at dinucleotide microsatellite loci in humans.

Microsatellites are a major type of molecular markers in genetics studies. Their mutational dynamics are not clear. We investigated the patterns and characteristics of 97 mutation events unambiguously identified, from 53 multigenerational pedigrees with 630 subjects, at 362 autosomal dinucleotide microsatellite loci. A size-dependent mutation bias (in which long alleles are biased toward contraction, whereas short alleles are biased toward expansion) is observed. There is a statistically significant negative relationship between the magnitude (repeat numbers changed during mutation) and direction (contraction or expansion) of mutations and standardized allele size. Contrasting with earlier findings in humans, most mutation events (63%) in our study are multistep events that involve changes of more than one repeat unit. There was no correlation between mutation rate and recombination rate. Our data indicate that mutational dynamics at microsatellite loci are more complicated than the generalized stepwise mutation models.

Alleles↗
PubMed2002

A whole-genome linkage scan suggests several genomic regions potentially containing quantitative trait Loci for osteoporosis.

Osteoporosis is an important health problem, particularly in the elderly women. Bone mineral density (BMD) is a major determinant of osteoporosis. For a sample of 53 pedigrees that contain 1249 sibling pairs, 1098 grandparent-grandchildren pairs, and 2589 first cousin pairs, we performed a whole- genome linkage scan using 380 microsatellite markers to identify genomic regions that may contain quantitative trait loci (QTL) of BMD. Each pedigree was ascertained through a proband with BMD values belonging to the bottom 10% of the population. We conducted two-point and multipoint linkage analyses. Several potentially important genomic regions were suggested. For example, the genomic region near the marker D10S1651 may contain a QTL for hip BMD variation (with two-point analysis LOD score of 1.97 and multipoint analysis LOD score of 2.29). The genomic regions near the markers D4S413 and D12S1723 may contain QTLs for spine BMD variation (with two-point analysis LOD score of 2.12 and 2.17 and multipoint analysis LOD score of 3.08 and 2.96, respectively). The genomic regions identified in this and some earlier reports are compared for exploration in extension studies with larger samples and/or denser markers for confirmation and fine mapping to eventually identify major functional genes involved in osteoporosis.

Bone Density↗