Identification of Proteins Important for Male Osteoporosis

Summary

Principal Investigator: Hong Wen Deng
Abstract: DESCRIPTION (provided by applicant): Identification of Proteins Important for Male Osteoporosis Osteoporosis is a major public health problem, mainly characterized by low bone mineral density (BMD). Variation of BMD is largely genetically determined (heritability of >60%). Some BMD genes/genomic regions are gender specific. Although women have lower BMD than men, men suffer significantly higher mortality rate upon osteoporotic fractures. However, studies on osteoporosis have largely been focused on women. Few genetic epidemiological studies and no proteomic epidemiological study on osteoporosis have been performed on men. Bone marrow mesenchymal stem cells (BMMSCs) and peripheral blood monocytes (PBMs) are precursors for osteoblasts (bone formation cells) and osteoclasts (bone resorption cells), respectively. Proteomics is a powerful state-of-the-art strategy in genetic dissection of complex diseases, such as osteoporosis. However, a major problem affecting the power of current most proteomic studies is the limited detection of low abundance proteins and proteins with extreme isoelectric point, molecular weight, and hydrophobicity, especially membrane proteins. A NOVEL approach to this problem is subcellular proteome extraction to stepwise isolate proteins from membrane, cytosol, nucleus, and cytoskeleton E fractions followed by sensitive 2D-nanoLC-ESI-MS/MS for fractioning and identifying significant proteins. Our hypothesis is that changes in the protein expression profiles in BMMSCs and PBMs underlie molecular mechanisms of BMD variation and are associated with osteoporosis in men. Our major goals here are to identify proteins differentially expressed in BMMSCs and PBMs in men with high vs. low BMD and thus identify proteins (and their genes) associated with male osteoporosis in BMMSCs and PBMs. We will recruit 120 otherwise healthy Caucasian males at peak bone mass ages of 25-50, including 60 subjects with low and 60 with high BMD (age matched population bottom or top 20% respectively in terms of BMD). Half of the sample (30 low vs. 30 high BMD subjects) will serve as the "discovery cohort" and the other half (30 low vs. 30 high BMD subjects) will serve as the "replication cohort". We will take fresh bone marrow and peripheral blood samples from each male subject, as we do in our ongoing NIH SCOR projects for female subjects. BMMSCs and PBMs will be isolated by subcellular proteome extraction for membrane proteins together with proteins of cytosolic, nuclear, and cytoskeletal fractions. Proteomic profiling experiments and analyses will be performed on the isolated protein samples from the discovery E cohort using 2D-nanoLC-ESI-MS/MS . Significant differentially expressed proteins identified will be verified by Western blotting using samples from the replication cohort. The major results (particularly those obtained from PBMs) of this study may be used to design customary diagnostic protein antibody chips and/or protein markers for prognosis of male osteoporosis. In combination with our ongoing projects for identifying risk genes of osteoporosis through genome-wide DNA association scan and genome-wide mRNA expression study of osteogenic cells, this study will powerfully and efficiently identify genes and some of their functions for male osteoporosis. PUBLIC HEALTH RELEVANCE: Osteoporosis is a disease with severe bone loss and a significantly increased risk of low trauma fractures. Male osteoporosis, compared with female osteoporosis, has higher mortality rate upon fractures. This project aims to identify proteins that are important to male osteoporosis. The findings will provide essential scientific basis for effective prevention, diagnosis and treatment of the disease.
Funding Period: 2009-09-18 - 2014-07-31
more information: NIH RePORT

Top Publications

  1. pmc Mutant ZP1 in familial infertility
    Hua Lin Huang
    From the Institute of Reproduction and Stem Cell Engineering, Central South University H L H, C L, W L, G X L, H M X, Reproductive and Genetic Hospital of CITIC Xiangya W L, G X L, H M X, and the First High School of Changsha X T, Changsha, and Xiamen Maternal and Child Health Care Hospital X M H, P L and PLA Hospital No 174 A G S, Xiamen all in China the Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans H L H, Y C Z, H W D and the School of Medicine, University of Missouri Kansas City, Kansas City C J P
    N Engl J Med 370:1220-6. 2014
  2. pmc Genome-wide pathway association studies of multiple correlated quantitative phenotypes using principle component analyses
    Feng Zhang
    Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Faculty of Public Health, College of Medicine, Xi an Jiaotong University, Xi an, Shaanxi, China
    PLoS ONE 7:e53320. 2012
  3. pmc Genome-wide association study identified UQCC locus for spine bone size in humans
    Fei Yan Deng
    Center of Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, PR China
    Bone 53:129-33. 2013
  4. pmc Copy number variation on chromosome 10q26.3 for obesity identified by a genome-wide study
    Tie Lin Yang
    Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi an Jiaotong University, Xi an 710049, People s Republic of China
    J Clin Endocrinol Metab 98:E191-5. 2013
  5. pmc Suggestion of GLYAT gene underlying variation of bone size and body lean mass as revealed by a bivariate genome-wide association study
    Yan Fang Guo
    School of Basic Medical Science, Institute of Bioinformatics, Southern Medical University, Guangzhou, People s Republic of China
    Hum Genet 132:189-99. 2013
  6. pmc Gene-gene interaction between RBMS3 and ZNF516 influences bone mineral density
    Tie Lin Yang
    Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi an Jiaotong University, Xi an, PR China
    J Bone Miner Res 28:828-37. 2013
  7. ncbi Bivariate genome-wide association study suggests fatty acid desaturase genes and cadherin DCHS2 for variation of both compressive strength index and appendicular lean mass in males
    Yingying Han
    Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Yangpu District, Shanghai, PR China
    Bone 51:1000-7. 2012
  8. pmc Genome-wide association study identified CNP12587 region underlying height variation in Chinese females
    Yin Ping Zhang
    Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, College of Medicine, Xi an Jiaotong University, Xi an, PR China
    PLoS ONE 7:e44292. 2012
  9. pmc Identification of genes for complex diseases using integrated analysis of multiple types of genomic data
    Hongbao Cao
    Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, United States of America
    PLoS ONE 7:e42755. 2012
  10. pmc Genome-wide copy number variation association analyses for age at menarche
    Yao Zhong Liu
    Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana 70112, USA
    J Clin Endocrinol Metab 97:E2133-9. 2012

Research Grants

  1. ROBUST AND POWERFUL TEST OF CANDIDATE GENES TO BONE MASS
    Hong Wen Deng; Fiscal Year: 2013
  2. Economics of Health, Wealth, and Well-Being
    DAVID A WISE; Fiscal Year: 2013
  3. HORMONAL CONTROL OF CALCIUM METABOLISM
    John T Potts; Fiscal Year: 2013
  4. The Role of Podocalyxin in Osteoclast Activity and Bone Metabolism
    Megan M Weivoda; Fiscal Year: 2013
  5. The Virtual Physiological Rat Project
    Daniel A Beard; Fiscal Year: 2013
  6. Epigenomewide DNA Methylation Study for Osteoporosis Risk
    Hong Wen Deng; Fiscal Year: 2013
  7. SPORE in Soft Tissue Sarcoma
    Samuel Singer; Fiscal Year: 2013
  8. Genetics of Bone Structure and Metabolism
    Michael C Mahaney; Fiscal Year: 2013
  9. Signaling in Inflammation, Stress, and Tumorigenesis
    GEORGE ROBERT STARK; Fiscal Year: 2013
  10. DIABETES AND ENDOCRINOLOGY RESEARCH CENTER
    Domenico Accili; Fiscal Year: 2013

Detail Information

Publications64

  1. pmc Mutant ZP1 in familial infertility
    Hua Lin Huang
    From the Institute of Reproduction and Stem Cell Engineering, Central South University H L H, C L, W L, G X L, H M X, Reproductive and Genetic Hospital of CITIC Xiangya W L, G X L, H M X, and the First High School of Changsha X T, Changsha, and Xiamen Maternal and Child Health Care Hospital X M H, P L and PLA Hospital No 174 A G S, Xiamen all in China the Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans H L H, Y C Z, H W D and the School of Medicine, University of Missouri Kansas City, Kansas City C J P
    N Engl J Med 370:1220-6. 2014
    ....
  2. pmc Genome-wide pathway association studies of multiple correlated quantitative phenotypes using principle component analyses
    Feng Zhang
    Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Faculty of Public Health, College of Medicine, Xi an Jiaotong University, Xi an, Shaanxi, China
    PLoS ONE 7:e53320. 2012
    ..We aim to provide a applicable MPPAS approach, which may help to gain deep understanding the potential biological mechanism of association results for complex diseases...
  3. pmc Genome-wide association study identified UQCC locus for spine bone size in humans
    Fei Yan Deng
    Center of Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, PR China
    Bone 53:129-33. 2013
    ..This study identified a novel locus, i.e., the UQCC gene, for spine BS variation in humans. Future functional studies will contribute to elucidating the mechanisms by which UQCC regulates bone growth and development...
  4. pmc Copy number variation on chromosome 10q26.3 for obesity identified by a genome-wide study
    Tie Lin Yang
    Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi an Jiaotong University, Xi an 710049, People s Republic of China
    J Clin Endocrinol Metab 98:E191-5. 2013
    ..However, a large proportion of the heritability of obesity remains unexplained. Copy number variations (CNVs) might contribute to the missing heritability of obesity...
  5. pmc Suggestion of GLYAT gene underlying variation of bone size and body lean mass as revealed by a bivariate genome-wide association study
    Yan Fang Guo
    School of Basic Medical Science, Institute of Bioinformatics, Southern Medical University, Guangzhou, People s Republic of China
    Hum Genet 132:189-99. 2013
    ..Our findings, together with the prior biological evidence, suggest the importance of GLYAT gene in co-regulation of bone phenotypes and body lean mass...
  6. pmc Gene-gene interaction between RBMS3 and ZNF516 influences bone mineral density
    Tie Lin Yang
    Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi an Jiaotong University, Xi an, PR China
    J Bone Miner Res 28:828-37. 2013
    ..043), but the direction of the effect was opposite to that observed in the three Caucasian samples. By providing evidence for genetic interactions underlying BMD, this study further delineates the genetic architecture of osteoporosis...
  7. ncbi Bivariate genome-wide association study suggests fatty acid desaturase genes and cadherin DCHS2 for variation of both compressive strength index and appendicular lean mass in males
    Yingying Han
    Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Yangpu District, Shanghai, PR China
    Bone 51:1000-7. 2012
    ..Our findings provide new insights into our understanding of the genetic basis of bone metabolism and the pathogenesis of osteoporosis...
  8. pmc Genome-wide association study identified CNP12587 region underlying height variation in Chinese females
    Yin Ping Zhang
    Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, College of Medicine, Xi an Jiaotong University, Xi an, PR China
    PLoS ONE 7:e44292. 2012
    ..We aim to identify sequence variants associated with adult height by a genome-wide association study of copy number variants (CNVs) in Chinese...
  9. pmc Identification of genes for complex diseases using integrated analysis of multiple types of genomic data
    Hongbao Cao
    Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, United States of America
    PLoS ONE 7:e42755. 2012
    ....
  10. pmc Genome-wide copy number variation association analyses for age at menarche
    Yao Zhong Liu
    Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana 70112, USA
    J Clin Endocrinol Metab 97:E2133-9. 2012
    ..The genetic basis and the mechanism for AAM are largely unknown. Copy number variation (CNV) is a common type of genetic variation underlying human complex traits. The importance of CNV to AAM variation is unclear...
  11. ncbi Significant association between body composition phenotypes and the osteocalcin genomic region in normative human population
    Michael Korostishevsky
    Human Population Biology Research Unit, Department of Anatomy and Anthropology, Tel Aviv University, Tel Aviv, Israel
    Bone 51:688-94. 2012
    ..Bioinformatics sources suggest that the aforementioned interaction could originate from different genetic loci in this region; however, ascertaining the exact circumstances requires a detailed molecular-genetic study...
  12. ncbi Bivariate genome-wide association study suggests that the DARC gene influences lean body mass and age at menarche
    Rong Hai
    Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai 200093, China
    Sci China Life Sci 55:516-20. 2012
    ..005) was identified. The SNP is located at the upstream of DARC (Duffy antigen receptor for chemokines) gene, suggesting that DARC may play an important role in regulating the metabolisms of both LBM and AAM...
  13. pmc A family-based association study identified CYP17 as a candidate gene for obesity susceptibility in Caucasians
    H Yan
    Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi an Jiaotong University, Xi an, Shaanxi, P R China
    Genet Mol Res 11:1967-74. 2012
    ..In conclusion, we suggest that the CYP17 gene has an effect on obesity in the Caucasian population. Further independent studies will be needed to confirm our findings...
  14. pmc Factors predicting vitamin D response variation in non-Hispanic white postmenopausal women
    Lan Juan Zhao
    Department of Biostatistics and Bioinformatics, Center for Bioinformatics and Genomics, Tulane University, New Orleans, Louisiana 70112, USA
    J Clin Endocrinol Metab 97:2699-705. 2012
    ..Understanding factors affecting the response variation is important for identifying subjects who are susceptible to vitamin D deficiency or toxicity. This study aimed to evaluate potential predictors for vitamin D response variation...
  15. pmc The impact of imputation on meta-analysis of genome-wide association studies
    Jian Li
    School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, United States of America
    PLoS ONE 7:e34486. 2012
    ..Our study may aid in the planning, data analysis, and interpretation of GWAS meta-analysis results when genotype imputation is necessary...
  16. pmc Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture
    Joo Yeon Hwang
    Center for Genome Science, National Institute of Health, Chungcheongbuk Do, Republic of Korea
    J Med Genet 50:212-9. 2013
    ..To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population...
  17. pmc Identification of genes for complex diseases by integrating multiple types of genomic data
    Hongbao Cao
    Department of Biomedical Engineering, Tulane University, New Orleans, USA
    Conf Proc IEEE Eng Med Biol Soc 2012:5541-4. 2012
    ....
  18. pmc Genome-wide association study identified copy number variants important for appendicular lean mass
    Shu Ran
    Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, People s Republic of China
    PLoS ONE 9:e89776. 2014
    ..In summary, our study suggested two novel CNVs and the related genes that may contribute to variation in ALM...
  19. pmc Trps1 differentially modulates the bone mineral density between male and female mice and its polymorphism associates with BMD differently between women and men
    Lishi Wang
    Department of Orthopedic Surgery and Biomedical Engineering, Campbell Clinic, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America Department of Basic Medicine, Inner Mongolia Medical University, Huhhot, Inner Mongolia, P R China
    PLoS ONE 9:e84485. 2014
    ..SNP analysis identified a nonsynonymous SNP (rs32398060) in Trps1 that co-segregated with bone mineral density. Analysis of association between this SNP within TRPS1 and BMD in a human population confirmed its significance. ..
  20. pmc Critical assessment of coalescent simulators in modeling recombination hotspots in genomic sequences
    Tao Yang
    Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street, Suite 2001, New Orleans, LA 70112, USA
    BMC Bioinformatics 15:3. 2014
    ..A plethora of coalescent simulators are developed, but selecting the most appropriate program remains challenging...
  21. pmc Multistage genome-wide association meta-analyses identified two new loci for bone mineral density
    Lei Zhang
    Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, China
    Hum Mol Genet 23:1923-33. 2014
    ....
  22. pmc On individual genome-wide association studies and their meta-analysis
    Yu Fang Pei
    Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, 200093, People s Republic of China
    Hum Genet 133:265-79. 2014
    ....
  23. pmc Meta-analysis of genome-wide association data identifies novel susceptibility loci for obesity
    Yu Fang Pei
    Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai 200093, P R China
    Hum Mol Genet 23:820-30. 2014
    ..Our results provide additional insights into the molecular genetic basis of obesity and may provide future targets for effective prevention and therapeutic intervention. ..
  24. pmc On genome-wide association studies and their meta-analyses: lessons learned from osteoporosis studies
    Yong Jun Liu
    Center for Bioinformatics and Genomics, and Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana 70112, USA
    J Clin Endocrinol Metab 98:E1278-82. 2013
    ..However, inconsistent findings are seen among and between GWASs and meta-analyses, and inconsistencies have even been observed between meta-analyses whose samples overlapped to a large extent...
  25. pmc Characterization of the DNA methylome and its interindividual variation in human peripheral blood monocytes
    Hui Shen
    Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA
    Epigenomics 5:255-69. 2013
    ..However, the DNA methylation landscape in PBMs is largely unknown. In this study, we characterized epigenome-wide DNA methylation profiles in purified PBMs...
  26. pmc SNP rs6265 regulates protein phosphorylation and osteoblast differentiation and influences BMD in humans
    Fei Yan Deng
    Center of Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, PR China Center for Bioinformatics and Genomics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA
    J Bone Miner Res 28:2498-507. 2013
    ..This study represents our first endeavor to dissect the functions of phosSNPs in bone, which might stimulate extended large-scale studies on bone or similar studies on other human complex traits and diseases...
  27. pmc CNV-TV: a robust method to discover copy number variation from short sequencing reads
    Junbo Duan
    Department of Biomedical Engineering, Tulane University, New Orleans, LA, USA
    BMC Bioinformatics 14:150. 2013
    ..However, the performances of these methods are not robust under some conditions, e.g., some of them may fail to detect CNVs of short sizes. There has been a strong demand for reliable detection of CNVs from high resolution NGS data...
  28. pmc Bivariate genome-wide association analyses identified genes with pleiotropic effects for femoral neck bone geometry and age at menarche
    Shu Ran
    Center of System Biomedical Sciences, School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, PR China
    PLoS ONE 8:e60362. 2013
    ..e. NRCAM, IDS and LOC148145), suggesting these three genes may co-regulate FNGPs and AAM. Our findings may help improve the understanding of genetic architecture and pathophysiological mechanisms underlying both osteoporosis and AAM...
  29. pmc Comprehensive characterization of human genome variation by high coverage whole-genome sequencing of forty four Caucasians
    Hui Shen
    Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA
    PLoS ONE 8:e59494. 2013
    ..Our results contribute towards a comprehensive characterization of human genomic variation, especially for less-common and rare variants, and provide an invaluable resource for future genetic studies of human variation and diseases...
  30. pmc Comparative studies of copy number variation detection methods for next-generation sequencing technologies
    Junbo Duan
    Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, United States of America
    PLoS ONE 8:e59128. 2013
    ..The computational demands are also studied. The results of our work provide a comprehensive evaluation on the performances of the selected CNV detection methods, which will help biological investigators choose the best possible method...
  31. pmc On combining reference data to improve imputation accuracy
    Jun Chen
    Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, United States of America
    PLoS ONE 8:e55600. 2013
    ..Our study is helpful in guiding application of imputation methods in next generation association analyses...
  32. pmc Ethnic differentiation of copy number variation on chromosome 16p12.3 for association with obesity phenotypes in European and Chinese populations
    T L Yang
    Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi an Jiaotong University, Xi an, China
    Int J Obes (Lond) 37:188-90. 2013
    ..3, for association with obesity in Europeans. The aim of this study was to directly examine the relationship between the CNV 16p12.3 and obesity phenotypes, including body mass index (BMI) and body fat mass...
  33. pmc Are bone mineral density loci associated with hip osteoporotic fractures? A validation study on previously reported genome-wide association loci in a Chinese population
    Y Guo
    Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Orthopaedics, School of Medicine, School of Life Science and Technology, The First Affiliated Hospital, Xi an Jiaotong University, Xi an, PR China
    Genet Mol Res 11:202-10. 2012
    ....
  34. pmc Genetic variants in the SOX6 gene are associated with bone mineral density in both Caucasian and Chinese populations
    T L Yang
    Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi an Jiaotong University, Xi an 710049, People s Republic of China
    Osteoporos Int 23:781-7. 2012
    ..We identified many single-nucleotide polymorphisms (SNPs) within or near the SOX6 gene to be significantly associated with hip bone mineral density (BMD)...
  35. ncbi Copy number variations at the Prader-Willi syndrome region on chromosome 15 and associations with obesity in whites
    Yuan Chen
    The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi an Jiaotong University, Xi an, Shaanxi, The People s Republic of China
    Obesity (Silver Spring) 19:1229-34. 2011
    ..Further studies are warranted to validate these CNVs and their importance to obesity...
  36. ncbi A genome wide association study between copy number variation (CNV) and human height in Chinese population
    Xi Li
    Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, China
    J Genet Genomics 37:779-85. 2010
    ..Our results expand our knowledge of the genetic factors underlying height variation and the biological regulation of human height...
  37. ncbi A genome-wide association analysis implicates SOX6 as a candidate gene for wrist bone mass
    Lijun Tan
    Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China
    Sci China Life Sci 53:1065-72. 2010
    ..20×10(-6) for rs11023787. Results of this study, together with the functional relevance of SOX6 in cartilage formation, support the SOX6 gene as an important gene for BMD variation...
  38. ncbi Alteration of vitamin D metabolic enzyme expression and calcium transporter abundance in kidney involved in type 1 diabetes-induced bone loss
    Y Zhang
    Center of System Biomedical Sciences, School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, People s Republic of China
    Osteoporos Int 22:1781-8. 2011
    ..The results revealed the alteration of vitamin D metabolic enzyme expression and the downregulation of renal calcium transporter abundance in type 1 diabetic mice...
  39. pmc Polymorphisms in predicted miRNA binding sites and osteoporosis
    Shu Feng Lei
    Laboratory of Molecular and Statistical, College of Life Sciences, Hunan Normal University, Changsha, Hunan, People s Republic of China
    J Bone Miner Res 26:72-8. 2011
    ....
  40. pmc The regulation-of-autophagy pathway may influence Chinese stature variation: evidence from elder adults
    Feng Pan
    The Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi an Jiaotong University, Xi an, Shaanxi, China
    J Hum Genet 55:441-7. 2010
    ..Our findings also implied that multiple-genetic factors may work jointly as a functional unit (pathway), and the traditional GWASs could have missed important genetic information imbedded in those less significant markers...
  41. pmc Biological pathway-based genome-wide association analysis identified the vasoactive intestinal peptide (VIP) pathway important for obesity
    Yong Jun Liu
    University of Missouri Kansas City, School of Medicine, Kansas City, Missouri, USA
    Obesity (Silver Spring) 18:2339-46. 2010
    ..The study also highlights the importance of pathway-based GWA analysis in identification of additional genes/variants for complex human diseases...
  42. pmc Molecular genetic studies of gene identification for osteoporosis: the 2009 update
    Xiang Hong Xu
    Institute of Molecular Genetics, Xi an Jiaotong University, Shaanxi, People s Republic of China
    Endocr Rev 31:447-505. 2010
    ..Comments are made on the notable findings and representative studies for their potential influence and implications on our present understanding of the genetics of osteoporosis...
  43. pmc Impact of female cigarette smoking on circulating B cells in vivo: the suppressed ICOSLG, TCF3, and VCAM1 gene functional network may inhibit normal cell function
    Feng Pan
    The Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi an Jiaotong University, Xi an, Shaanxi, 710049, People s Republic of China
    Immunogenetics 62:237-51. 2010
    ..Our results highlight the potential usage of integrated analyses for unveiling the novel pathogenesis mechanism and emphasized the significance of B cells in the etiology of smoking-induced disease...
  44. pmc Pathway-based genome-wide association analysis identified the importance of regulation-of-autophagy pathway for ultradistal radius BMD
    Lishu Zhang
    Institute of Bioscience and Biotechnology, School of Science, Beijing Jiaotong University, Beijing, People s Republic of China
    J Bone Miner Res 25:1572-80. 2010
    ..Further functional evaluation of this pathway to determine the mechanism by which it regulates wrist BMD should be pursued to provide new insights into the pathogenesis of wrist osteoporosis...
  45. pmc Genome-wide association study for femoral neck bone geometry
    Lan Juan Zhao
    Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, USA
    J Bone Miner Res 25:320-9. 2010
    ..Significant association between a nearby common SNP, rs10514713 of the RTP3 gene, and hip fracture (P = 1.0 x 10(-3)) was found. Our observations suggest that RTP3 may be a novel candidate gene for femoral neck bone geometry...
  46. ncbi Bivariate association analysis for quantitative traits using generalized estimation equation
    Fang Yang
    Hunan Normal University, Changsha, China
    J Genet Genomics 36:733-43. 2009
    ..This method is robust and yields false-positive rates close to the pre-set nominal significance level. Our real data analyses attested to the usefulness of the method...
  47. pmc Genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians
    F Y Deng
    School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USA
    Osteoporos Int 21:579-87. 2010
    ..Important risk factors for OF include reduced bone mineral density and unstable bone structure. This genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians...
  48. pmc Comparative studies of de novo assembly tools for next-generation sequencing technologies
    Yong Lin
    Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai 200093, P R China
    Bioinformatics 27:2031-7. 2011
    ....
  49. ncbi Molecular genetic studies of gene identification for sarcopenia
    Li Jun Tan
    Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, People s Republic of China
    Hum Genet 131:1-31. 2012
    ....
  50. pmc Genome-wide association study of copy number variants suggests LTBP1 and FGD4 are important for alcohol drinking
    Yu Fang Pei
    Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, People s Republic of China
    PLoS ONE 7:e30860. 2012
    ..Our results provide suggestive evidence that the newly identified CNV regions and relevant genes may contribute to the genetic mechanism of alcohol dependence...
  51. pmc A follow-up association study of two genetic variants for bone mineral density variation in Caucasians
    L S Zhang
    College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, 100044, People s Republic of China
    Osteoporos Int 23:1867-75. 2012
    ..We found that variant rs7776725 is consistently associated with hip, spine, wrist and whole-body BMD, which highlights the potential importance of this variant or linked variants for osteoporosis...
  52. pmc The fat mass and obesity associated gene, FTO, is also associated with osteoporosis phenotypes
    Yan Guo
    Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi an Jiaotong University, Xi an, People s Republic of China
    PLoS ONE 6:e27312. 2011
    ..Our findings, together with the prior biological evidence, suggest that the FTO gene might be a new candidate for BMD variation and osteoporosis in Chinese populations...
  53. pmc Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians
    H Li
    Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People s Republic of China
    Diabetologia 55:981-95. 2012
    ..To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians...
  54. pmc Bivariate genome-wide association analyses of femoral neck bone geometry and appendicular lean mass
    Lu Sun
    Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, China
    PLoS ONE 6:e27325. 2011
    ..However, the specific SNPs/genes shared by these phenotypes are largely unknown...
  55. pmc Genome-wide association study of copy number variation identified gremlin1 as a candidate gene for lean body mass
    Rong Hai
    Center of System Biomedical Sciences, University of Shanghai for Science and Technology, 516 Jungong Road, Shanghai, PR China
    J Hum Genet 57:33-7. 2012
    ..Our results suggest that the gremlin1 gene is a potentially important gene for LBM variation. Our findings also show the utility and efficacy of CNV as genetic markers in association studies...
  56. pmc Testing rare variants for association with diseases: a Bayesian marker selection approach
    Lei Zhang
    Center of System Biomedical Sciences, University of Shanghai for Science and Technology, P R China
    Ann Hum Genet 76:74-85. 2012
    ..Simulation studies show that the proposed method has improved power over several existing methods in certain conditions. Analyses of two empirical datasets demonstrate its applicability...
  57. ncbi Genome-wide association study identifies HMGN3 locus for spine bone size variation in Chinese
    Shu Feng Lei
    Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, People s Republic of China
    Hum Genet 131:463-9. 2012
    ..The SNPs in the region of HMGN3 gene formed a tightly combined haplotype block in both Chinese and Caucasians. The results suggest that the genomic region containing HMGN3 gene may be associated with spine BS in Chinese...
  58. pmc Peripheral blood monocyte-expressed ANXA2 gene is involved in pathogenesis of osteoporosis in humans
    Fei Yan Deng
    Center of Bioinformatics and Genomics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA
    Mol Cell Proteomics 10:M111.011700. 2011
    ..In conclusion, this study identified a novel osteoporosis susceptibility gene ANXA2, and suggested a novel pathophysiological mechanism, mediated by ANXA2, for osteoporosis in humans...
  59. pmc Copy number variation in CNP267 region may be associated with hip bone size
    Shan lin Liu
    Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, People s Republic of China
    PLoS ONE 6:e22035. 2011
    ..Our findings suggest that CNP267 region may be associated with hip BS which might influence the FHL2 gene downstream...
  60. pmc An integrative study ascertained SOD2 as a susceptibility gene for osteoporosis in Chinese
    Fei Yan Deng
    Laboratory of Molecular and Statistical Genetics and Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, People s Republic of China
    J Bone Miner Res 26:2695-701. 2011
    ..05), suggesting that they are expression quantitative trait loci (eQTLs) regulating SOD2 gene expression. In conclusion, this integrative evidence from DNA, RNA, and protein levels support SOD2 as a susceptibility gene for osteoporosis...
  61. pmc Mitochondria-wide association study of common variants in osteoporosis
    Yan Guo
    Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Molecular Genetics, School of Life Science and Technology, Xi an Jiaotong University, PR China
    Ann Hum Genet 75:569-74. 2011
    ..Subjects classified as haplogroup X had significantly lower hip BMD values than others (P= 0.040). Our results highlighted the importance of mtDNA variants in osteoporosis...
  62. pmc Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures
    Yin Ping Zhang
    The Key Laboratory of Environment and Genes Related to Diseases, Xi an Jiaotong University College of Medicine, Ministry of Education, Xi an, Shaanxi, People s Republic of China
    PLoS ONE 6:e21835. 2011
    ..This study aims to verify the potential association between hip OF and TRAIL pathway...
  63. pmc Genetic association study of common mitochondrial variants on body fat mass
    Tie Lin Yang
    Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi an Jiaotong University, Xi an, Shaanxi, People s Republic of China
    PLoS ONE 6:e21595. 2011
    ..86 and 6.03, respectively. Our findings suggest that common variants in mitochondria might play a role in variations of body fat mass. Further molecular and functional studies will be needed to clarify the potential mechanism...
  64. pmc Replication study of candidate genes/loci associated with osteoporosis based on genome-wide screening
    Y P Zhang
    Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, College of Medicine, Xi an Jiaotong University, Xi an, People s Republic of China
    Osteoporos Int 21:785-95. 2010
    ..Ten SNPs achieved combined p < 3.6 x 10(-4)...

Research Grants31

  1. ROBUST AND POWERFUL TEST OF CANDIDATE GENES TO BONE MASS
    Hong Wen Deng; Fiscal Year: 2013
    ..abstract_text> ..
  2. Economics of Health, Wealth, and Well-Being
    DAVID A WISE; Fiscal Year: 2013
    ..Subproject 8 explores ways of Improving Health and Health Care for Minority and Aging Populations. ..
  3. HORMONAL CONTROL OF CALCIUM METABOLISM
    John T Potts; Fiscal Year: 2013
    ....
  4. The Role of Podocalyxin in Osteoclast Activity and Bone Metabolism
    Megan M Weivoda; Fiscal Year: 2013
    ..Additionally, studying the role of sex steroids in the Vav/PODXLdel bone phenotype may elucidate mechanisms that contribute to postmenopausal and age-related bone loss. ..
  5. The Virtual Physiological Rat Project
    Daniel A Beard; Fiscal Year: 2013
    ..This proposal targets the grand challenge of understanding complex multi-faceted disease phenotypes through experiments and simulations that capture the complex genotype-environment-phenotype relationship. ..
  6. Epigenomewide DNA Methylation Study for Osteoporosis Risk
    Hong Wen Deng; Fiscal Year: 2013
    ..Therefore, the results will be highly important for understanding the underlying molecular mechanisms, and thus help prevention and treatment, of osteoporosis. ..
  7. SPORE in Soft Tissue Sarcoma
    Samuel Singer; Fiscal Year: 2013
    ..abstract_text> ..
  8. Genetics of Bone Structure and Metabolism
    Michael C Mahaney; Fiscal Year: 2013
    ..risk - in humans in general, as well as those with effects more specific to peoples from an understudied region of the world. ..
  9. Signaling in Inflammation, Stress, and Tumorigenesis
    GEORGE ROBERT STARK; Fiscal Year: 2013
    ..abstract_text> ..
  10. DIABETES AND ENDOCRINOLOGY RESEARCH CENTER
    Domenico Accili; Fiscal Year: 2013
    ....
  11. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013
    ..abstract_text> ..
  12. TOXIC SUBSTANCES IN THE ENVIRONMENT
    Martyn T Smith; Fiscal Year: 2013
    ..The program will be overseen and coordinated by an Administration core (A). ..
  13. Mitochondrial Dysfunction in Neurodegeneration of Aging
    Gary E Gibson; Fiscal Year: 2013
    ..Successful completion of the goals of these projects can be expected to provide new insights into neurodegenerative processes and contribute to novel approaches to ameliorating age-related neurodegenerations. ..
  14. Cellular Senescence and Aging
    James L Kirkland; Fiscal Year: 2013
    ..Our approach will provide timely, innovative, and clinically relevant interventional results based on addressing the fundamental question of the role of cellular senescence that has remained unanswered for many years. ..
  15. UNMC EPPLEY CANCER CENTER SUPPORT GRANT
    Kenneth H Cowan; Fiscal Year: 2013
    ....
  16. PHYSIOLOGY OF BONE METABOLISM IN AN AGING POPULATION
    Sundeep Khosla; Fiscal Year: 2013
    ..Collectively, these studies strive to provide a comprehensive assesment of the pathogenesis and clinical impact of one of the most important disorders facing our aging population. ..
  17. The Role Of Osteoclast PODXL, A Mediator Of Cell Adhesion, In Bone Metabolism
    Merry Jo Oursler; Fiscal Year: 2013
    ....