Biomedical subjects

Peng-Yuan Liu

Publications and source records attributed to Peng-Yuan Liu.

At least 19 recordsLinked to original sources

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

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↗

PubMed2006

Impacts of QTL x environment interactions on genetic response to marker-assisted selection.

Genotype x environment (GE) interaction is a common characteristic for quantitative traits, and has been a subject of great concern for breeding programs. Simulation studies were conducted to investigate the effects of GE interaction on genetic response to marker-assisted selection (MAS). In our study we demonstrated that MAS is generally more efficient than phenotypic selection in the presence of GE interaction, and this trend is more pronounced for developing broadly adaptable varieties. The utilization of different QTL information dramatically influences MAS efficiency. When MAS is based on QTLs evaluated in a single environment, the causal QTL x environment (QE) interactions usually reduce general response across environments, and the reduction in the cumulative general response is a function of the proportion of QE interactions for the trait studied. However, MAS using QTL information evaluated in multiple environments not only yields higher general response, but the general response obtained is also reasonably robust to QE interactions. The total response achieved by MAS in a specific environment depends largely on the total heritability of traits and is slightly subject to relative changes between general heritability and GE interaction heritability. Two breeding strategies, breeding experiments conducted in one environment throughout and in two environments alternately, were also examined for the implementation of marker-based selection. It was thus concluded that plant breeders should be cautious to utilize QTL information from only one environment and execute breeding studies in another.

Breeding↗

PubMed2006

Polymorphisms of the vitamin D receptor gene predict the onset of surgical menopause in Caucasian females.

We tested association of four single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene (VDR) with age at surgical and natural menopause in a sample of Caucasians composed of 153 women with surgical and 260 with natural menopause. A significant association was observed between age at surgical menopause and two SNPs, rs1544410 (BsmI) and rs731236 (TaqI) (p < 0.05). For rs1544410, homozygotes of the minor allele, AA, had about two-fold higher risk of surgical menopause than homozygotes of the major allele, GG (95% confidence ratio (CI) 1.09-3.82). For rs731236, the CC subjects had a greater chance of surgical menopause than the TT subjects (odds ratio = 2.01, 95% CI 1.07-3.78). Since rs1544410 and rs731236 are in strong linkage disequilibrium, the haplotypes based on these two loci were also tested. The haplotype AC was highly significantly associated with age at surgical menopause (p = 0.008). Women with this haplotype had surgical menopause on average 2.8 years earlier than non-carriers. These results reveal the potential effect of the VDR gene on ovaries and uterus, and suggest that its SNPs can be used as predictors of genetic susceptibility for early surgical menopause and respective causal health problems.

Age of Onset↗

PubMed2006

A gene expression signature predicts survival of patients with stage I non-small cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer-related death in the United States. Nearly 50% of patients with stages I and II non-small cell lung cancer (NSCLC) will die from recurrent disease despite surgical resection. No reliable clinical or molecular predictors are currently available for identifying those at high risk for developing recurrent disease. As a consequence, it is not possible to select those high-risk patients for more aggressive therapies and assign less aggressive treatments to patients at low risk for recurrence. METHODS AND FINDINGS: In this study, we applied a meta-analysis of datasets from seven different microarray studies on NSCLC for differentially expressed genes related to survival time (under 2 y and over 5 y). A consensus set of 4,905 genes from these studies was selected, and systematic bias adjustment in the datasets was performed by distance-weighted discrimination (DWD). We identified a gene expression signature consisting of 64 genes that is highly predictive of which stage I lung cancer patients may benefit from more aggressive therapy. Kaplan-Meier analysis of the overall survival of stage I NSCLC patients with the 64-gene expression signature demonstrated that the high- and low-risk groups are significantly different in their overall survival. Of the 64 genes, 11 are related to cancer metastasis (APC, CDH8, IL8RB, LY6D, PCDHGA12, DSP, NID, ENPP2, CCR2, CASP8, and CASP10) and eight are involved in apoptosis (CASP8, CASP10, PIK3R1, BCL2, SON, INHA, PSEN1, and BIK). CONCLUSIONS: Our results indicate that gene expression signatures from several datasets can be reconciled. The resulting signature is useful in predicting survival of stage I NSCLC and might be useful in informing treatment decisions.

Algorithms↗

PubMed2005

Association analysis of estrogen receptor alpha gene polymorphisms with cross-sectional geometry of the femoral neck in Caucasian nuclear families.

Bone geometry is a key factor in bone strength, which is the ultimate intrinsic determinant of fracture risk. Though the heritability of bone geometry is high, little effort has been spent on searching for the underlying genes. In this study, employing a sample of 1,873 subjects from 405 Caucasian nuclear families, we studied seven single nucleotide polymorphisms (SNPs) and their haplotypes of the ER-alpha gene for association with six hip geometric variables, namely, cross-sectional area (CSA), cortical thickness (CT), endocortical diameter (ED), subperiosteal width (W), sectional modulus (Z) and buckling ratio (BR). The major method used was the quantitative transmission disequilibrium test (QTDT). Our major findings were summarized below. The within-family association between SNP4 (rs1801132) in exon 4 with endocortical diameter and subperiosteal width was detected in single locus analyses (P=0.008 and 0.021, respectively) and verified in haplotype analyses (P=0.034 and 0.058, respectively). The total association of SNP4 with these two diameters was also observed in both single locus and haplotype analyses (P=0.005 and 0.031 for ED, plus P=0.003 and 0.070 for W). In addition, the total association between SNP5 (rs932477) in intron 4 with cortical thickness and buckling ratio was detected (single locus analyses: P=0.035 and 0.041, respectively). Haplotype analyses further supported the above association (P=0.010 and 0.004, respectively). Similar patterns of associations with the studied SNPs and their haplotypes were present in subsamples stratified by sex, too. However, after permutation tests, the empirical significance level was set as P<0.011, which renders most associations insignificant. Therefore, we concluded that polymorphisms in the ER-alpha gene were nominally associated with femoral neck (FN) geometry variables estimated from DXA. Such genetic effects on hip geometry were not sex specific.

Adult↗

PubMed2005

Predictive factors for age at menopause in Caucasian females.

OBJECTIVE: Early onset of menopause results in the premature exposure to low estrogen levels and is associated with a number of postmenopausal health problems and higher risk of mortality. The aim of this study was to determine genetic and environmental factors associated with age at natural and surgical menopause. METHODS: Multiple regression analysis using a sample of Caucasians composed of 154 females with surgical and 248 with natural menopause. RESULTS: Breastfeeding is a significant predictor of earlier natural menopause (P<0.05). Use of oral contraceptives and smoking were not significantly associated with age at menopause. Females who did not have history of pregnancies are at significantly higher risk (P<0.001) of getting early surgical menopause than those who did. We also tested the association of seven single nucleotide polymorphisms (SNPs) of the estrogen receptor alpha (ER-alpha) gene with age at menopause. No association was observed with age at menopause but the PvuII p allele was overrepresented in women with surgical menopause and associated with menopause per se (P=0.029; OR=1.8, 95% CI=1.1-3.0). CONCLUSIONS: Breastfeeding and alcohol consumption are significantly associated with earlier natural menopause. No significant effects of the ER-alpha genotypes were observed on the age of menopause. Given the important role of the ER-alpha in estrogen signaling, which directly influences the menopausal process, further studies are required to better define the relationship between this gene and age at menopause.

Age of Onset↗

PubMed2005

Improvement of mapping accuracy by unifying linkage and association analysis.

It is well known that pedigree/family data record information on the coexistence in founder haplotypes of alleles at nearby loci and the cotransmission from parent to offspring that reveal different, but complementary, profiles of the genetic architecture. Either conventional linkage analysis that assumes linkage equilibrium or family-based association tests (FBATs) capture only partial information, leading to inefficiency. For example, FBATs will fail to detect even very tight linkage in the case where no allelic association exists, while a violation of the assumption of linkage equilibrium will result in biased estimation and reduced efficiency in linkage mapping. In this article, by using a data augmentation technique and the EM algorithm, we propose a likelihood-based approach that embeds both linkage and association analyses into a unified framework for general pedigree data. Relative to either linkage or association analysis, the proposed approach is expected to have greater estimation accuracy and power. Monte Carlo simulations support our theoretical expectations and demonstrate that our new methodology: (1) is more powerful than either FBATs or classic linkage analysis; (2) can unbiasedly estimate genetic parameters regardless of whether association exists, thus remedying the bias and less precision of traditional linkage analysis in the presence of association; and (3) is capable of identifying tight linkage alone. The new approach also holds the theoretical advantage that it can extract statistical information to the maximum extent and thereby improve mapping accuracy and power because it integrates multilocus population-based association study and pedigree-based linkage analysis into a coherent framework. Furthermore, our method is numerically stable and computationally efficient, as compared to existing parametric methods that use the simplex algorithm or Newton-type methods to maximize high-order multidimensional likelihood functions, and also offers the computation of Fisher's information matrix. Finally, we apply our methodology to a genetic study on bone mineral density (BMD) for the vitamin D receptor (VDR) gene and find that VDR is significantly linked to BMD at the one-third region of the wrist.

Algorithms↗

PubMed2005

Mapping quantitative trait loci for cross-sectional geometry at the femoral neck.

UNLABELLED: A genome-wide linkage scan was performed in a sample of 79 multiplex pedigrees to identify genomic regions linked to femoral neck cross-sectional geometry. Potential quantitative trait loci were detected at several genomic regions, such as 10q26, 20p12-q12, and chromosome X. INTRODUCTION: Bone geometry is an important determinant of bone strength and osteoporotic fractures. Previous studies have shown that femoral neck cross-sectional geometric variables are under genetic controls. To identify genetic loci underlying variation in femoral neck cross-sectional geometry, we conducted a whole genome linkage scan for four femoral neck cross-sectional geometric variables in 79 multiplex white pedigrees. MATERIALS AND METHODS: A total of 1816 subjects from 79 pedigrees were genotyped with 451 microsatellite markers across the human genome. We performed linkage analyses on the entire data, as well as on men and women separately. RESULTS: Significant linkage evidence was identified at 10q26 for buckling ratio (LOD = 3.27) and Xp11 (LOD = 3.45) for cortical thickness. Chromosome region 20p12-q12 showed suggestive linkage with cross-sectional area (LOD = 2.33), cortical thickness (LOD = 2.09), and buckling ratio (LOD = 1.94). Sex-specific linkage analyses further supported the importance of 20p12-q12 for cortical thickness (LOD = 2.74 in females and LOD = 1.88 in males) and buckling ratio (LOD = 5.00 in females and LOD = 3.18 in males). CONCLUSIONS: This study is the first genome-wide linkage scan searching for quantitative trait loci underlying femoral neck cross-sectional geometry in humans. The identification of the genes responsible for bone geometric variation will improve our knowledge of bone strength and aid in development of diagnostic approaches and interventions for osteoporotic fractures.

Absorptiometry, Photon↗

PubMed2005

Association tests of interleukin-6 (IL-6) and type II tumor necrosis factor receptor (TNFR2) genes with bone mineral density in Caucasians using a re-sampling approach.

Interleukin 6 (IL-6) and tumor necrosis factor (TNF) are important cytokines for bone turnover. In this study, a promoter C-174G single-nucleotide polymorphism (SNP) within the IL-6 gene affecting the transcription rate of IL-6 and an exon 6 T676G SNP of the TNF receptor 2 (TNFR2) gene causing an M196R amino-acid change were examined for their relationship with bone mineral density (BMD). Four hundred and five multi-offspring Caucasian families, including 389 male children and 744 female children, were used. One thousand re-samplings were conducted and in each data set, one child was randomly chosen from each family. For each data set, one-way analysis of variance (ANOVA) test was independently implemented using age, age2, sex, height and weight as covariates. There were 523, 288, 204 and 369 significant results out of 1,000-replicate re-samplings of the data of the IL-6 SNP (P<0.05) for one-third, mid-distal, ultradistal radius BMD, and the first principal component (PC1) extracted from the three radial BMDs, respectively, which means that the confidences for associations of the C-174G SNP in the IL-6 gene with one-third, mid-distal, ultradistal radius (totally called distal forearm) BMDs, and PC1, were 52.3, 28.8, 20.4 and 36.9%, respectively. For this SNP with BMD at other skeletal sites and the TNFR2 T676G SNP with BMD at any site, significant results were far less than 200 times out of 1,000 re-sampling replicates. The exceedingly consistent permutation results further improved the confidence of the associations. It may imply that the IL-6 C-174G SNP is associated with distal forearm BMD, but there is no evidence that the TNFR2 T676G SNP is related with BMD in US Caucasians. This is the first attempt to conduct association test utilizing a re-sampling approach. Our results may be more informative than other association analyses that were only based on one sampling result. The results also suggest that different samplings could produce significantly diverse results even for the same population and the results from one sampling are unlikely to be conclusive. Our results have significant implications for association studies and interpretation of non-reproducible association findings.

Body Weights and Measures↗

PubMed2005

Hotelling's T2 multivariate profiling for detecting differential expression in microarrays.

The most widely used statistical methods for finding differentially expressed genes (DEGs) are essentially univariate. In this study, we present a new T(2) statistic for analyzing microarray data. We implemented our method using a multiple forward search (MFS) algorithm that is designed for selecting a subset of feature vectors in high-dimensional microarray datasets. The proposed T2 statistic is a corollary to that originally developed for multivariate analyses and possesses two prominent statistical properties. First, our method takes into account multidimensional structure of microarray data. The utilization of the information hidden in gene interactions allows for finding genes whose differential expressions are not marginally detectable in univariate testing methods. Second, the statistic has a close relationship to discriminant analyses for classification of gene expression patterns. Our search algorithm sequentially maximizes gene expression difference/distance between two groups of genes. Including such a set of DEGs into initial feature variables may increase the power of classification rules. We validated our method by using a spike-in HGU95 dataset from Affymetrix. The utility of the new method was demonstrated by application to the analyses of gene expression patterns in human liver cancers and breast cancers. Extensive bioinformatics analyses and cross-validation of DEGs identified in the application datasets showed the significant advantages of our new algorithm.

Algorithms↗

PubMed2005

Linkage and association analyses of the UCP3 gene with obesity phenotypes in Caucasian families.

Uncoupling protein 3 (UCP3) uncouples ATP production from mitochondrial respiration, thereby dissipating energy as heat and affecting the efficiency of energy metabolism. Genetic variations in the UCP3 gene have been conceived to affect body weight in the general population. In this study, using the quantitative transmission disequilibrium test (QTDT), we assessed linkage and association between the UCP3 gene and obesity phenotypes in a large sample of 1,873 subjects from 405 United States Caucasian nuclear families. Obesity phenotypes tested include body mass index (BMI), fat mass, percent fat mass (PFM), and lean mass, with the latter three measured by dual-energy X-ray absorptiometry. We first selected five single nucleotide polymorphisms (SNPs) and then analyzed three highly polymorphic ones, namely, -55 C/T (promoter), Tyr99Tyr (exon 3), and Tyr210Tyr (exon 5), in the total sample. Significant linkage disequilibria (0.392 <or= D' <or= 0.940, P < 0.0001) were observed between pairs of SNPs. In single-locus analyses, we found statistically significant association (P = 0.034) and linkage (P = 0.031) between -55 C/T and BMI. This polymorphism explains 2.29% of BMI variation, and subjects carrying the T allele had an average of 3.5% lower BMI than those without it (P = 0.003). In haplotype analyses, we also observed evidence of linkage (P = 0.002) and association (P = 0.035) with BMI. In summary, our results suggest that UCP3 gene polymorphisms may contribute to BMI variation in this Caucasian population.

Alleles↗

PubMed2004

Quantifying the relationship between gene expressions and trait values in general pedigrees.

Treating mRNA transcript abundances as quantitative traits and examining their relationships with clinical traits have been pursued by using an analytical approach of quantitative genetics. Recently, Kraft et al. presented a family expression association test (FEXAT) for correlation between gene expressions and trait values with a family-based (sibships) design. This statistic did not account for biological relationships of related subjects, which may inflate type I error rate and/or decrease power of statistical tests. In this article, we propose two new test statistics based on a variance-components approach for analyses of microarray data obtained from general pedigrees. Our methods accommodate covariance between relatives for unmeasured genetic effects and directly model covariates of clinical importance. The efficacy and validity of our methods are investigated by using simulated data under different sample sizes, family sizes, and family structures. The proposed LR method has correct type I error rate with moderate to large sample sizes regardless of family structure and family sizes. It has higher power with complex pedigrees and similar power to the FEXAT with sibships. The other proposed FEXAT(R) method is favorable with large family sizes, regardless of sample sizes and family structure. Our methods, robust to population stratification, are complementary to the FEXAT in expression-trait association studies.

Animals↗

PubMed2004

APOE haplotypes influence bone mineral density in Caucasian males but not females.

Low bone mineral density (BMD) is one of the most important risk factors for osteoporosis. Apolipoprotein E (APOE) has been considered as a candidate gene for osteoporosis because of its influence on osteoblast uptake of lipoprotein-borne vitamin K. Using the quantitative transmission disequilibrium test QTDT, we examined linkage and/or association of APOE and BMD at the lumbar spine and the total hip in a sample of 387 Caucasian nuclear families with 715 parents and 953 children. The children were aged 20-50 years and female offspring were premenopausal as well. Four single nucleotide polymorphisms (SNP1-4) in the APOE gene, 4-locus haplotypes and 2-locus haplotypes (epsilon1, epsilon2, epsilon3, epsilon4 isoforms, reconstructed by SNP3 and SNP4) were analyzed. In the whole sample and the female offspring families we found no evidence of linkage or association for either single SNP or haplotype with BMD at the two studied skeletal sites. In the male offspring families, within-family associations were observed at the haplotypes CGTC (P = 0.001), GGTT (P = 0.002), and GATC (P = 0.006) for the lumbar spine BMD, and GATC (P = 0.008) for the total hip BMD. These data suggested that in our studied Caucasian population, APOE may have effects on BMD variation in males but not females. Further studies with a larger sample size are required to confirm such results.

Absorptiometry, Photon↗

PubMed2004

Tests of linkage and/or association of TGF-beta1 and COL1A1 genes with bone mass.

Transforming growth factor beta 1 (TGF-beta1) is involved in bone metabolism and collagen type I alpha 1 (COL1A1) is the most abundant protein of bone matrix. Both have been considered as candidate genes for osteoporosis. In this study, we employed the transmission disequilibrium test (TDT) to examine the relationship between each of the two genes with bone mineral density (BMD) and bone mineral content (BMC) at the spine and hip in a sample of 1668 subjects from 387 Caucasian nuclear families. For the TGF-beta1 gene, three SNPs, SNP1, SNP2, and SNP4 (located in exon 1, intron 4 and intron 5, respectively) were tested and the minor allele frequencies were 30.9%, 2.1% and 27.0%, respectively. All eight possible haplotypes (TGF1-8) were observed. For the COL1A1 gene, the minor allele frequencies of SNP5, SNP6 and SNP8 (located in exon 1, intron 1, and exon 45, respectively) were 15.2%, 18.7%, 2.0%, respectively, and only six of eight potential haplotypes (COL1-6) were obtained. In the whole sample, total associations were observed between haplotype COL5 with spine BMD (P=0.027), haplotypes COL3 and TGF4 with hip BMC (P=0.002, 0.003, respectively). Within-family associations were found for spine BMD at haplotypes TGF4 (P=0.027) in female offspring families and TGF3 (P=0.021) in male offspring families. Further studies with denser markers and larger sample size are required to eventually define the relationship between these two genes with bone mass at the spine and hip.

Adult↗

PubMed2004

Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes.

BACKGROUND: The adequacy of association studies for complex diseases depends critically on the existence of linkage disequilibrium (LD) between functional alleles and surrounding SNP markers. RESULTS: We examined the patterns of LD and haplotype distribution in eight candidate genes for osteoporosis and/or obesity using 31 SNPs in 1,873 subjects. These eight genes are apolipoprotein E (APOE), type I collagen alpha1 (COL1A1), estrogen receptor-alpha (ER-alpha), leptin receptor (LEPR), parathyroid hormone (PTH)/PTH-related peptide receptor type 1 (PTHR1), transforming growth factor-beta1 (TGF-beta1), uncoupling protein 3 (UCP3), and vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR). Yin yang haplotypes, two high-frequency haplotypes composed of completely mismatching SNP alleles, were examined. To quantify LD patterns, two common measures of LD, D' and r2, were calculated for the SNPs within the genes. The haplotype distribution varied in the different genes. Yin yang haplotypes were observed only in PTHR1 and UCP3. D' ranged from 0.020 to 1.000 with the average of 0.475, whereas the average r2 was 0.158 (ranging from 0.000 to 0.883). A decay of LD was observed as the intermarker distance increased, however, there was a great difference in LD characteristics of different genes or even in different regions within gene. CONCLUSION: The differences in haplotype distributions and LD patterns among the genes underscore the importance of characterizing genomic regions of interest prior to association studies.

Apolipoproteins E↗

PubMed2004

Tests of linkage and/or association of the LEPR gene polymorphisms with obesity phenotypes in Caucasian nuclear families.

Genetic variations in the leptin receptor (LEPR) gene have been conceived to affect body weight in general populations. In this study, using the tests implemented in the statistical package QTDT, we evaluated association and/or linkage of the LEPR gene with obesity phenotypes in a large sample comprising 1,873 subjects from 405 Caucasian nuclear families. Obesity phenotypes tested include body mass index (BMI), fat mass, percentage fat mass (PFM), and lean mass, with the latter three measured by dual-energy X-ray absorptiometry (DXA). Three single nucleotide polymorphisms (SNPs), namely Lys109Arg (A/G), Lys656Asn (G/C), Pro1019Pro (G/A), in the LEPR gene were analyzed. Significant linkage disequilibrium (0.394 < or = |D'| < or = 0.688, P < 0.001) was observed between pairs of the three SNPs. No significant population stratification was found for any SNP/phenotype. In single-locus analyses, evidence of association was observed for Lys656Asn with lean mass (P = 0.002) and fat mass (P = 0.015). The contribution of this polymorphism to the phenotypic variation of lean mass and fat mass was 2.63% and 1.15%, respectively. Subjects carrying allele G at the Lys656Asn site had, on average, 3.16% higher lean mass and 2.71% higher fat mass than those without it. In the analyses for haplotypes defined by the three SNPs, significant associations were detected between haplotype GCA (P = 0.005) and lean mass. In addition, marginally significant evidence of association was observed for this haplotype with fat mass (P = 0.012). No statistically significant linkage was found, largely due to the limited power of the linkage approach to detect small genetic effects in our data sets. Our results suggest that the LEPR gene polymorphisms contribute to variation in obesity phenotypes.

Adult↗

PubMed2004

A major gene model of adult height is suggested in Chinese.

Adult height (stature), as a complex quantitative trait, has been studied in different populations. However, few genetic studies on height were performed on the Chinese, the largest population in the world. In this study, familial correlation and segregation analyses were carried out for adult height in a Chinese sample composed of 385 nuclear families with a total of 1,169 informative individuals. The results suggest that a major gene with a recessive effect accounts for about 17.2% of the total adult height variation in the Chinese. Significant familial residual effects are found. The heritability (+/-SE) of height is estimated to be 0.647 (+/-0.122). This study, for the first time, provides evidence for the high degree of genetic determination of adult height in the Chinese population and furnishes a valuable reference for further mapping and identification of adult height genes in the Chinese.

Adult↗