H Yan

Publications (5)29.97 Total impact

• Article: A family-based association study identified CYP17 as a candidate gene for obesity susceptibility in Caucasians.

  H Yan, Y Guo, T-L Yang, L-J Zhao, H-W Deng
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  ABSTRACT: The cytochrome P450c17α gene (CYP17) encodes a key biosynthesis enzyme of estrogen, which is critical in regulating adipogenesis and adipocyte development in humans. We therefore hypothesized that CYP17 is a candidate gene for predicting obesity. In order to test this hypothesis, we performed a family-based association test to investigate the relationship between the CYP17 gene and obesity phenotypes in a large sample comprising 1873 subjects from 405 Caucasian nuclear families of European origin recruited by the Osteoporosis Research Center of Creighton University, USA. Both single SNPs and haplotypes were tested for associations with obesity-related phenotypes, including body mass index (BMI) and fat mass. We identified three SNPs to be significantly associated with BMI, including rs3740397, rs6163, and rs619824. We further characterized the linkage disequilibrium structure for CYP17 and found that the whole CYP17 gene was located in a single-linkage disequilibrium block. This block was observed to be significantly associated with BMI. A major haplotype in this block was significantly associated with both BMI and fat mass. 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.
  Genetics and molecular research: GMR 05/2012; 11(3):1967-74. · 1.18 Impact Factor
• Article: Erratum to: Genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians.

  F-Y Deng, L J Zhao, Y-F Pei, B-Y Sha, X-G Liu, H Yan, L Wang, T L Yang, R R Recker, C J Papasian, H W Deng
  Osteoporosis International 04/2010; · 4.58 Impact Factor
• Source

  Available from: PubMed Central

  Article: Genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians.

  F-Y Deng, L-J Zhao, Y-F Pei, B-Y Sha, X-G Liu, H Yan, L Wang, T-L Yang, R R Recker, C J Papasian, H-W Deng
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  ABSTRACT: Osteoporotic fracture (OF) is a serious outcome of osteoporosis. 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. Bone mineral density (BMD) and femoral neck cross-sectional geometric parameters (FNCSGPs) are under strong genetic control. DNA copy number variation (CNV) is an important source of genetic diversity for human diseases. This study aims to identify CNVs associated with BMD and FNCSGPs. Genome-wide CNV association analyses were conducted in 1,000 unrelated Caucasian subjects for BMD at the spine, hip, femoral neck, and for three FNCSGPs -cortical thickness (CT), cross-section area (CSA), and buckling ratio (BR). BMD was measured by dual energy X-ray absorptiometry (DEXA). CT, CSA, and BR were estimated using DEXA measurements. Affymetrix 500K arrays and copy number analysis tool was used to identify CNVs. A CNV in VPS13B gene was significantly associated with spine, hip and FN BMDs, and CT, CSA, and BR (p < 0.05). Compared to subjects with two copies of the CNV, carriers of one copy had an average of 14.6%, 12.4%, and 13.6% higher spine, hip, and FN BMD, 20.0% thicker CT, 10.6% larger CSA, and 12.4% lower BR. Thus, a decrease of the CNV consistently produced stronger bone, thereby reducing osteoporotic fracture risk. VPS13B gene, via affecting BMD and FNCSGPs, is a novel osteoporosis risk gene.
  Osteoporosis International 09/2009; 21(4):579-87. · 4.58 Impact Factor
• Article: Genome-wide association analyses suggested a novel mechanism for smoking behavior regulated by IL15.

  Y-Z Liu, Y-F Pei, Y-F Guo, L Wang, X-G Liu, H Yan, D-H Xiong, Y-P Zhang, S Levy, J Li, C K Haddock, C J Papasian, Q Xu, J Z Ma, T J Payne, R R Recker, M D Li, H-W Deng
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  ABSTRACT: Cigarette smoking is the leading preventable cause of death in the United States. Although smoking behavior has a significant genetic determination, the specific genes and associated mechanisms underlying the smoking behavior are largely unknown. Here, we carried out a genome-wide association study on smoking behavior in 840 Caucasians, including 417 males and 423 females, in which we examined approximately 380,000 single nucleotide polymorphisms (SNPs). We found that a cluster of nine SNPs upstream from the IL15 gene were associated with smoking status in males, with the most significant SNP, rs4956302, achieving a P-value (8.80 x 10(-8)) of genome-wide significance. Another SNP, rs17354547 that is highly conserved across multiple species achieved a P-value of 5.65 x 10(-5). These two SNPs, together with two additional SNPs (rs1402812 and rs4956396) were selected from the above nine SNPs for replication in an African-American sample containing 1251 subjects, including 412 males and 839 females. The SNP rs17354547 was replicated successfully in the male subgroup of the replication sample; it was associated with smoking quantity (SQ), the Heaviness of Smoking Index (HSI) and the Fagerstrom Test for Nicotine Dependence (FTND), with P-values of 0.031, 0.0046 and 0.019, respectively. In addition, a haplotype formed by rs17354547, rs1402812 and rs4956396 was also associated with SQ, HSI and FTND, achieving P-values of 0.039, 0.0093 and 0.0093, respectively. To further confirm our findings, we carried out an in silico replication study of the nine SNPs in a Framingham Heart Study sample containing 7623 Caucasians from 1731 families, among which, 3491 subjects were males and 4132 were females. Again, the male-specific association with smoking status was observed, for which seven of the nine SNPs achieved significant P-values (P<0.05) and two achieved marginally significant P-values (P<0.10) in males. Several of the nine SNPs, including the highly conserved one across species, rs17354547, are located at potential transcription factor binding sites, suggesting transcription regulation as a possible function for these SNPs. Through this function, the SNPs may modulate the gene expression of IL15, a key cytokine regulating immune function. As the immune system has long been recognized to influence drug addiction behavior, our association findings suggest a novel mechanism for smoking addiction involving immune modulation through the IL15 pathway.
  Molecular psychiatry 02/2009; 14(7):668-80. · 15.05 Impact Factor
• Source

  Available from: cof.org.cn

  Article: Comparison of whole genome linkage scans in premenopausal and postmenopausal women: no bone-loss-specific QTLs were implicated.

  H Yan, Y-J Liu, Q Zhou, P Xiao, R R Recker, H-W Deng
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  ABSTRACT: This study was conducted to investigate if there exist bone-loss-specific quantitative trait loci (QTLs) for females. Genome-wide linkage scans were conducted in total, premenopausal, and postmenopausal women, respectively. No QTLs exclusively were found in postmenopausal women, suggesting that no bone-loss-specific QTL was implicated independent of BMD in our sample. Bone mineral density (BMD) in elderly women is determined jointly by peak bone mass achieved before menopause and by subsequent bone loss upon and after menopause. Peak bone mass is under strong genetic control, but whether bone loss has genetic determination independent of peak BMD is unknown. To investigate if there exist bone-loss-specific quantitative trait loci (QTLs) for females, we conducted genome-wide linkage scans in 2,582 Caucasian females from 451 pedigrees including 1,486 premenopausal and 1,096 postmenopausal women. Linkage analyses were performed in the total sample and premenopausal and postmenopausal women subgroups, respectively, and the results were compared. No linkage evidence was found exclusively in postmenopausal women. Linkage signals identified are largely consistent in the total, premenopausal, and postmenopausal samples. For example, for spine BMD, for the total sample, a significant linkage was obtained on 15q13 (LOD = 3.67), and LOD scores of 1.52 and 2.49 were achieved on 15q13 in premenopausal and postmenopausal women, respectively. We did not find any QTLs exclusively in postmenopausal women; hence, no specific QTL for bone loss was implicated independent of BMD in our female sample.
  Osteoporosis International 10/2008; 20(5):771-7. · 4.58 Impact Factor