title: 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 x 10(-8)) and rs7832552 (p = 7.58 x 10(-8)), 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 x 10(-9) for rs16892496 and 3.88 x 10(-10) 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.
authors.affiliation: The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an Shaanxi, P R China.
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Liu
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Tan
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Lei
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Guo
authors.forename: Dong-Hai
authors.initials: DH
authors.lastname: Xiong
authors.forename: Xiang-Ding
authors.initials: XD
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.forename: Tie-Lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Yin-Ping
authors.initials: YP
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Tang
authors.forename: Xue-Zhen
authors.initials: XZ
authors.lastname: Zhu
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Deng
authors.forename: Shawn
authors.initials: S
authors.lastname: Levy
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Papasian
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000328:Adult; D000368:Aged; D001213:Asian; D001823:Body Composition / Q000235:genetics*; D001835:Body Weight / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D013851:Thinness; D044465:White People
chemical_list: D018025:Receptors, Thyrotropin-Releasing Hormone