****2篇文章同登《Cell》子刊

　　

生物通报道，最新一期的《Cell》子刊《American Journal of Human Genetics》同期刊发了两篇中国学者的文章，文章标题分别为：Genome-wide Association and Replication Studies Identified TRHR as an Important Gene for Lean Body Mass和Genome-wide Association and Follow-Up Replication Studies Identified ADAMTS18 and TGFBR3 as Bone Mass Candidate Genes in Different Ethnic Groups。

 

两篇文章的通讯作者同为****，特聘教授邓红文博士。

 

Genome-Wide Association and Replication Studies Identified TRHR as an Important Gene for Lean Body Mass文章的第一作者是西安交通大学生命科学院青年教授刘晓刚，刘晓刚在硕士、博士期间师从贺西京教授和邓红文教授，现在是生命科学院生物医学信息工程教育部重点实验室的青年教师。

 

该论文对少肌症（Sarcopenia）这一老年性疾病进行全基因组关联分析，在国际上首次发现促甲状腺激素释放激素受体（TRHR）基因变异，以及与生长激素-胰岛素样生长因子I基因变异之间的互作，对人群肌肉量变化具有显著影响，这个发现对揭示少肌症的发病机理具有重要的意义。

 

Genome-wide Association and Follow-Up Replication Studies Identified ADAMTS18 and TGFBR3 as Bone Mass Candidate Genes in Different Ethnic Groups文章的第一作者是密苏里大学基础医学与骨科学系的Dong-Hai Xiong，文章第二作者是刘晓刚。

 

该论文对骨质疏松症（bone mineral density，BMD）进行全基因组关联分析，同时选取了不同种族人群的骨样本，分别选取了美国白人，中国人，和非洲人的样本进行检测，结果发现ADAMTS18与TGFBR3与不同种族人群的骨质疏松症有很大的关联，这些成果为骨质疏松症疾病带来指导意义。

（生物通 小茜）

生物通推荐原文检索：Genome-Wide Association and Replication Studies Identified TRHR as an Important Gene for Lean Body Mass

【Abstract】

Low lean body mass (LBM) is related to a series of health problems, such as osteoporotic fracture and sarcopenia. Here we report a genome-wide association (GWA) study on LBM variation, by using Affymetrix 500K single-nucleotide polymorphism (SNP) arrays. In the GWA scan, we tested 379,319 eligible SNPs in 1,000 unrelated US whites and found that two SNPs, rs16892496 (p = 7.55  108) andrs7832552 (p = 7.58  108), within the thyrotropin-releasing hormone receptor (TRHR) gene were significantly associated with LBM. Subjects carrying unfavorable genotypes at rs16892496 and rs7832552 had, on average, 2.70 and 2.55 kg lower LBM, respectively, compared to those with alternative genotypes. We replicated the significant associations in three independent samples: (1) 1488 unrelated US whites, (2) 2955 Chinese unrelated subjects, and (3) 593 nuclear families comprising 1972 US whites. Meta-analyses of the GWA scan and the replication studies yielded p values of 5.53  109 for rs16892496 and 3.88  1010 for rs7832552. In addition, we found significant interactions between rs16892496 and polymorphisms of several other genes involved in the hypothalamic-pituitary-thyroid and the growth hormone-insulin-like growth factor-I axes. Results of this study, together with the functional relevance of TRHR in muscle metabolism, support the TRHR gene as an important gene for LBM variation.

 

生物通推荐原文检索：Genome-wide Association and Follow-Up Replication Studies Identified ADAMTS18 and TGFBR3 as Bone Mass Candidate Genes in Different Ethnic Groups

【Abstract】

To identify and validate genes associated with bone mineral density (BMD), which is a prominent osteoporosis risk factor, we tested 379,319 SNPs in 1000 unrelated white U.S. subjects for associations with BMD. For replication, we genotyped the most significant SNPs in 593 white U.S. families (1972 subjects), a Chinese hip fracture (HF) sample (350 cases, 350 controls), a Chinese BMD sample (2955 subjects), and a Tobago cohort of African ancestry (908 males). Publicly available Framingham genome-wide association study (GWAS) data (2953 whites) were also used for in silico replication. The GWAS detected two BMD candidate genes, ADAMTS18 (ADAM metallopeptidase with thrombospondin type 1 motif, 18) and TGFBR3 (transforming growth factor, beta receptor III). Replication studies verified the significant findings by GWAS. We also detected significant associations with hip fracture for ADAMTS18 SNPs in the Chinese HF sample. Meta-analyses supported the significant associations of ADAMTS18 and TGFBR3 with BMD (p values: 2.56  105 to 2.13  108; total sample size: n = 5925 to 9828). Electrophoretic mobility shift assay suggested that the minor allele of one significant ADAMTS18 SNP might promote binding of the TEL2 factor, which may repress ADAMTS18 expression. The data from NCBI GEO expression profiles also showed that ADAMTS18 and TGFBR3 genes were differentially expressed in subjects with normal skeletal fracture versus subjects with nonunion skeletal fracture. Overall, the evidence supports that ADAMTS18 and TGFBR3 might underlie BMD determination in the major human ethnic groups.