Background: Receptor activator of nuclear factor- κ B ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162)- b...Background: Receptor activator of nuclear factor- κ B ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162)- binds RANKL with high affinity and specificity and inhibits RANKL action. Methods: The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of- 1.8 to - 4.0 at the lumbar spine or- 1.8 to- 3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open- label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase. Results: Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C- telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent. Conclusions: In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis.展开更多
Background: When applied to trabecular bone X-ray images, a method for analyzing trabecular bone texture based on the initial slope of variogram (ISV) was used to assess the trabecular bone health. Methodology: Data f...Background: When applied to trabecular bone X-ray images, a method for analyzing trabecular bone texture based on the initial slope of variogram (ISV) was used to assess the trabecular bone health. Methodology: Data from more than two hundred subjects were retrospectively studied. For each subject, a DXA (GE Lunar Prodigy) scan of the forearm was performed, and bone mineral density (BMD) value was measured at the location of ultra-distal radius, X-ray digital image of the same forearm was taken on the same day, and ISV value over the same location of ultra-distal radius was calculated. Pearson’s correlation coefficients were calculated to examine the correlation between BMD and ISV of the trabecular bones located at the same ultra-distal radius. ISV values changed with subjects’ age were also reported. Results: The results show that ISV value was highly correlated with the DXA-measured BMD of the same trabecular bone located at the ultra-distal radius. The correlation coefficient between ISV and BMD with the 95% confident was 0.79 ± 0.09. They also demonstrated that the age-related changes in trabecular bone health and differentiated age patterns in males and females, respectively. The results showed that the decrease in BMD was accompanied by a decrease in the initial slope of variogram (ISV). Conclusions: This study suggests that ISV might be used to quantitatively evaluate trabecular health for osteoporosis and bone disease diagnosis.展开更多
Waterpipe(WP),a less common method of tobacco smoking than cigarette smoking(CS),has become increasingly popular over the last decade.Contrary to popular belief,WP smoking is far from harmless and has multiple health ...Waterpipe(WP),a less common method of tobacco smoking than cigarette smoking(CS),has become increasingly popular over the last decade.Contrary to popular belief,WP smoking is far from harmless and has multiple health risks similar to,or even exceeding,those seen in CS[1,2].展开更多
Background Genetic factors are important in the pathogenesis of osteoporosis,but less is known about the genetic determinants of osteoporosis treatment.We aimed to explore the association between the gene polymorphism...Background Genetic factors are important in the pathogenesis of osteoporosis,but less is known about the genetic determinants of osteoporosis treatment.We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase （FDPS） in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China.Methods The study group comprised 639 postmenopausal women aged （62.2＆#177;7.0） years with osteoporosis or osteopenia who had been randomly assigned to low dose group （70 mg/2w） or standard dose group （70 mg/w） of alendronate in this 1-year study.We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul.Before and after treatment,serum levels of calcium,phosphate,alkaline phosphatase （ALP）,cross linked C-telopeptide of type Ⅰ collagen （β-CTX） were detected.Bone mineral density （BMD） at lumbar spine and proximal femur was measured.The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD,bone turnover biomarkers after the treatment.Results The FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck,and patients with CC genotype had significantly higher baseline femoral neck BMD （（733.6＆#177;84.1） mg/cm2） than those with AC genotypes （（703.0＆#177;86.9） mg/cm2） and AA genotypes （（649.8＆#177;62.4） mg/cm2） （P 〈0.01）.No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS.The percentage change of serum ALP level was significantly lower in patients with CC genotype （-22.9%） than that in those with AC genotype （-24.1%） and AA genotype （-29.8%） of FDPS after 12 months of alendronate treatment （P 〈0.05）.Neither percentage change of BMD nor β-CTX level after alendronate treatment had association with FDPS genotype.Conclusions FDPS gene was probably a candidate gene to predict femoral neck BMD at baseline.FDPS gene alleles could predict change percentage of ALP after treatment of alendronate,but possibly had no significant relationship with the responsiveness of BMD to alendronate therapy.展开更多
Background Ethnicity is shown to be one of important factors affacting bone mineral density （BMD）. The present study was performed to compare the association of six markers for five candidate genes with BMD variatio...Background Ethnicity is shown to be one of important factors affacting bone mineral density （BMD）. The present study was performed to compare the association of six markers for five candidate genes with BMD variation in two populations of different ethnicity, Caucasian and Chinese, and the contribution of genotype and ethnicity to this variation in the populations. Methods The studied restriction fragment length polymorphisms were BsaH Ⅰ of the calcium-sensing receptor gene, Sac Ⅰ of the α2HS-glycoprotein （AHSG） gene, Pvu Ⅱ and Xba Ⅰ of the oestrogen receptor α gene, Apa Ⅰ of the vitamin D receptor （VDR） gene and BstB Ⅰ of the parathyroid hormone gene. The association of these markers with BMD was analysed by one-way and two-way ANOVA with adjustment for covariates. Results Two polymorphisms, AHSG-Sac Ⅰ and VDR-Apa Ⅰ , showed no association with BMD, while the others were associated with BMD variation at some skeletal sites in either males or females. The polymorphisms indicated clear distinctions between the associations depending on ethnicity, gender and skeletal site. Similar patterns were observed in their contribution to the total population BMD variation. Ethnicity appears to have a larger effect on the total population BMD variation in females than in males. It may account, on the average, for about 2% total population BMD variation at the spine of females and about 1% at the hip of males and females. Conclusion The results of the present study suggest that significant interethnic differentiation at some loci may contribute to the significant interethnic difference in BMD. However, this contribution apparently is not large.展开更多
Objective： To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. Methods： Microarray data generated from other study aiming...Objective： To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. Methods： Microarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpdng GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection （MCODE） were used to establish the protein-protein interaction （PPI） network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery （DAVID） was used for pathway analysis. Results： A total of 87 genes expressed differentially in D. melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway. Conclusion： Genes and their associated pathways in D. rnelanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curnumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.展开更多
Background Alcohol dependence （AD） is a complex disorder characterized by impaired control over drinking. It is determined by both genetic and environmental factors. The recent approach of genome-wide association st...Background Alcohol dependence （AD） is a complex disorder characterized by impaired control over drinking. It is determined by both genetic and environmental factors. The recent approach of genome-wide association study （GWAS） is a powerful tool for identifying complex disease-associated susceptibility alleles, however, a few GWASs have been conducted for AD, and their results are largely inconsistent. The present study aimed to screen the loci associated with alcohol-related phenotypes using GWAS technology. Methods A genome-wide association study with the behavior of regular alcohol drinking and alcohol consumption was performed to identify susceptibility genes associated with AD, using the Affymetrix 500K SNP array in an initial sample consisting of 904 unrelated Caucasian subjects. Then, the initial results in GWAS were replicated in three independent samples： 1972 Caucasians in 593 nuclear families, 761 unrelated Caucasian subjects, and 2955 unrelated Chinese Hans. Results Several genes were associated with the alcohol-related phenotypes at the genome-wide significance level, with the ankyrin repeat domain 7 gene （ANKRDT） showing the strongest statistical evidence for regular alcohol drinking and suggestive statistical evidence for alcohol consumption. In addition, certain haplotypes within the ANKRD7 and cytokine-likel （CYTL 1） genes were significantly associated with regular drinking behavior, such as one ANKRD7 block composed of the SNPs rs6466686-rs4295599-rs12531066 （P = 6.51×10^-8）. The association of alcohol consumption was successfully replicated with rs4295599 in ANKRD7 gene in independent Caucasian nuclear families and independent unrelated Chinese Hans, and with rs16836497 in CYTL1 gene in independent unrelated Caucasians. Meta-analyses based on both the GWAS and replication samples further supported the observed significant associations between the ANKRDTor CYTL1 gene and alcohol consumption. Conclusion The evidence suggests that ANKRD7 and CYTL 1 genes may play an important role in the variance in AD risk.展开更多
To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic an...To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic analysis and bivariate whole-genome linkage scan were carried out in a large Caucasian population. All the phenotypes studied were significantly controlled by genetic factors （P 〈 0.001） with the heritabilities ranging from 0.45 to 0.68. Significantly genetic correlations were found between TBFM and CSA （cross-section area）, W （sub-periosteal diameter）, Z （section modulus） and CT （cortical thickness） except between TBFM and BR （buckling ratio）. The peak bivariate LOD scores were 3.23 （20q12）, 2.47 （20p11）, 3.19 （6q27）, 1.68 （20p12）, and 2.47 （7q11） for the five pairs of TBFM and BR, CSA, CT, W, and Z in the entire sample, respectively. Gender-specific bivariate linkage evidences were also found for the five pairs. 6p25 had complete pleiotropic effects on the variations of TBFM ＆ Z in the female sub-population, and 6q27 and 17q11 had coincident link- ages for TBFM ＆ CSA and TBFM ＆ Z in the entire population. We identified moderate genetic correlations and several shared genomic regions between TBFM and FNGPs in a large Caucasian population.展开更多
基金supported by grants from the Cancer and Smoking Disease Research Bone Biology Programthe Nebraska Tobacco Settlement Biomedical Research Development Award,NIH grants(3R01CA129488-01A2S2 and AG14683)a grant from State of Nebraska Cancer and Smoking Disease Research Program(LB595)
文摘Background: Receptor activator of nuclear factor- κ B ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162)- binds RANKL with high affinity and specificity and inhibits RANKL action. Methods: The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of- 1.8 to - 4.0 at the lumbar spine or- 1.8 to- 3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open- label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase. Results: Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C- telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent. Conclusions: In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis.
文摘Background: When applied to trabecular bone X-ray images, a method for analyzing trabecular bone texture based on the initial slope of variogram (ISV) was used to assess the trabecular bone health. Methodology: Data from more than two hundred subjects were retrospectively studied. For each subject, a DXA (GE Lunar Prodigy) scan of the forearm was performed, and bone mineral density (BMD) value was measured at the location of ultra-distal radius, X-ray digital image of the same forearm was taken on the same day, and ISV value over the same location of ultra-distal radius was calculated. Pearson’s correlation coefficients were calculated to examine the correlation between BMD and ISV of the trabecular bones located at the same ultra-distal radius. ISV values changed with subjects’ age were also reported. Results: The results show that ISV value was highly correlated with the DXA-measured BMD of the same trabecular bone located at the ultra-distal radius. The correlation coefficient between ISV and BMD with the 95% confident was 0.79 ± 0.09. They also demonstrated that the age-related changes in trabecular bone health and differentiated age patterns in males and females, respectively. The results showed that the decrease in BMD was accompanied by a decrease in the initial slope of variogram (ISV). Conclusions: This study suggests that ISV might be used to quantitatively evaluate trabecular health for osteoporosis and bone disease diagnosis.
基金supported by the National Natural Science Foundation of China[82003401&81972981]the Key Projects of Colleges and Universities of Henan Education Department[21A330006]the Opening Foundation of National Health Commission Key Laboratory of Birth Defects Prevention and Henan Key Laboratory of Population Defects Prevention[ZD202001]。
文摘Waterpipe(WP),a less common method of tobacco smoking than cigarette smoking(CS),has become increasingly popular over the last decade.Contrary to popular belief,WP smoking is far from harmless and has multiple health risks similar to,or even exceeding,those seen in CS[1,2].
基金grants from the National Natural Science Foundation of China，National Key Program of Clinical Science
文摘Background Genetic factors are important in the pathogenesis of osteoporosis,but less is known about the genetic determinants of osteoporosis treatment.We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase （FDPS） in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China.Methods The study group comprised 639 postmenopausal women aged （62.2＆#177;7.0） years with osteoporosis or osteopenia who had been randomly assigned to low dose group （70 mg/2w） or standard dose group （70 mg/w） of alendronate in this 1-year study.We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul.Before and after treatment,serum levels of calcium,phosphate,alkaline phosphatase （ALP）,cross linked C-telopeptide of type Ⅰ collagen （β-CTX） were detected.Bone mineral density （BMD） at lumbar spine and proximal femur was measured.The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD,bone turnover biomarkers after the treatment.Results The FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck,and patients with CC genotype had significantly higher baseline femoral neck BMD （（733.6＆#177;84.1） mg/cm2） than those with AC genotypes （（703.0＆#177;86.9） mg/cm2） and AA genotypes （（649.8＆#177;62.4） mg/cm2） （P 〈0.01）.No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS.The percentage change of serum ALP level was significantly lower in patients with CC genotype （-22.9%） than that in those with AC genotype （-24.1%） and AA genotype （-29.8%） of FDPS after 12 months of alendronate treatment （P 〈0.05）.Neither percentage change of BMD nor β-CTX level after alendronate treatment had association with FDPS genotype.Conclusions FDPS gene was probably a candidate gene to predict femoral neck BMD at baseline.FDPS gene alleles could predict change percentage of ALP after treatment of alendronate,but possibly had no significant relationship with the responsiveness of BMD to alendronate therapy.
文摘Background Ethnicity is shown to be one of important factors affacting bone mineral density （BMD）. The present study was performed to compare the association of six markers for five candidate genes with BMD variation in two populations of different ethnicity, Caucasian and Chinese, and the contribution of genotype and ethnicity to this variation in the populations. Methods The studied restriction fragment length polymorphisms were BsaH Ⅰ of the calcium-sensing receptor gene, Sac Ⅰ of the α2HS-glycoprotein （AHSG） gene, Pvu Ⅱ and Xba Ⅰ of the oestrogen receptor α gene, Apa Ⅰ of the vitamin D receptor （VDR） gene and BstB Ⅰ of the parathyroid hormone gene. The association of these markers with BMD was analysed by one-way and two-way ANOVA with adjustment for covariates. Results Two polymorphisms, AHSG-Sac Ⅰ and VDR-Apa Ⅰ , showed no association with BMD, while the others were associated with BMD variation at some skeletal sites in either males or females. The polymorphisms indicated clear distinctions between the associations depending on ethnicity, gender and skeletal site. Similar patterns were observed in their contribution to the total population BMD variation. Ethnicity appears to have a larger effect on the total population BMD variation in females than in males. It may account, on the average, for about 2% total population BMD variation at the spine of females and about 1% at the hip of males and females. Conclusion The results of the present study suggest that significant interethnic differentiation at some loci may contribute to the significant interethnic difference in BMD. However, this contribution apparently is not large.
基金Supported by the National Natural Science Foundation of China(No.81102680)China Postdoctoral Science Foundation(No.20100470524)
文摘Objective： To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. Methods： Microarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpdng GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection （MCODE） were used to establish the protein-protein interaction （PPI） network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery （DAVID） was used for pathway analysis. Results： A total of 87 genes expressed differentially in D. melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway. Conclusion： Genes and their associated pathways in D. rnelanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curnumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.
基金This work was supported by grants from NIH （No. R21 AA015973, No. R21 AGO27110, No. R01 AR050496-01, No. R01 AG026564, and No. P50 AR055081）, National Science Foundation of China （No. 30771222 and No. 30731160618）, Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry of China （（2010） 609） and Innovative Program of Hunan Province （No. 2011TF1004）.
文摘Background Alcohol dependence （AD） is a complex disorder characterized by impaired control over drinking. It is determined by both genetic and environmental factors. The recent approach of genome-wide association study （GWAS） is a powerful tool for identifying complex disease-associated susceptibility alleles, however, a few GWASs have been conducted for AD, and their results are largely inconsistent. The present study aimed to screen the loci associated with alcohol-related phenotypes using GWAS technology. Methods A genome-wide association study with the behavior of regular alcohol drinking and alcohol consumption was performed to identify susceptibility genes associated with AD, using the Affymetrix 500K SNP array in an initial sample consisting of 904 unrelated Caucasian subjects. Then, the initial results in GWAS were replicated in three independent samples： 1972 Caucasians in 593 nuclear families, 761 unrelated Caucasian subjects, and 2955 unrelated Chinese Hans. Results Several genes were associated with the alcohol-related phenotypes at the genome-wide significance level, with the ankyrin repeat domain 7 gene （ANKRDT） showing the strongest statistical evidence for regular alcohol drinking and suggestive statistical evidence for alcohol consumption. In addition, certain haplotypes within the ANKRD7 and cytokine-likel （CYTL 1） genes were significantly associated with regular drinking behavior, such as one ANKRD7 block composed of the SNPs rs6466686-rs4295599-rs12531066 （P = 6.51×10^-8）. The association of alcohol consumption was successfully replicated with rs4295599 in ANKRD7 gene in independent Caucasian nuclear families and independent unrelated Chinese Hans, and with rs16836497 in CYTL1 gene in independent unrelated Caucasians. Meta-analyses based on both the GWAS and replication samples further supported the observed significant associations between the ANKRDTor CYTL1 gene and alcohol consumption. Conclusion The evidence suggests that ANKRD7 and CYTL 1 genes may play an important role in the variance in AD risk.
基金supported by grants from NIH in USA (No. K01 AR02170-01, R01 AR45349-01, R01 GM60402-01 A1, R01 AG026564-01A2, and R21 AG027110-01A1)the Natural Science Foundation o China (NSFC) (No. 30600364)The genotyping experiment was performed by Marshfield Center for Medical Genetics and supported by NHLB Mammalian Genotyping Service (Contract No. HV48141)
文摘To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic analysis and bivariate whole-genome linkage scan were carried out in a large Caucasian population. All the phenotypes studied were significantly controlled by genetic factors （P 〈 0.001） with the heritabilities ranging from 0.45 to 0.68. Significantly genetic correlations were found between TBFM and CSA （cross-section area）, W （sub-periosteal diameter）, Z （section modulus） and CT （cortical thickness） except between TBFM and BR （buckling ratio）. The peak bivariate LOD scores were 3.23 （20q12）, 2.47 （20p11）, 3.19 （6q27）, 1.68 （20p12）, and 2.47 （7q11） for the five pairs of TBFM and BR, CSA, CT, W, and Z in the entire sample, respectively. Gender-specific bivariate linkage evidences were also found for the five pairs. 6p25 had complete pleiotropic effects on the variations of TBFM ＆ Z in the female sub-population, and 6q27 and 17q11 had coincident link- ages for TBFM ＆ CSA and TBFM ＆ Z in the entire population. We identified moderate genetic correlations and several shared genomic regions between TBFM and FNGPs in a large Caucasian population.
