Abstract:
:Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34-52%) for TBLH-BMD, and 39% (95% CI: 30-48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29-56%). We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5. Variants in the TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that SREBF1 is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.Bone mineral density and lean skeletal mass are heritable traits. Here, Medina-Gomez and colleagues perform bivariate GWAS analyses of total body lean mass and bone mass density in children, and show genetic loci with pleiotropic effects on both traits.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Medina-Gomez C,Kemp JP,Dimou NL,Kreiner E,Chesi A,Zemel BS,Bønnelykke K,Boer CG,Ahluwalia TS,Bisgaard H,Evangelou E,Heppe DHM,Bonewald LF,Gorski JP,Ghanbari M,Demissie S,Duque G,Maurano MT,Kiel DP,Hsu YH,C J van ddoi
10.1038/s41467-017-00108-3subject
Has Abstractpub_date
2017-07-25 00:00:00pages
121issue
1issn
2041-1723pii
10.1038/s41467-017-00108-3journal_volume
8pub_type
杂志文章abstract::Anatomical atlases in standard coordinates are necessary for the interpretation and integration of research findings in a common spatial context. However, the two most-used mouse brain atlases, the Franklin-Paxinos (FP) and the common coordinate framework (CCF) from the Allen Institute for Brain Science, have accumula...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-13057-w
更新日期:2019-11-07 00:00:00
abstract::Drugs of abuse, including alcohol, ablate the expression of specific forms of long-term synaptic depression (LTD) at glutamatergic synapses in dorsal striatum (DS), a brain region involved in goal-directed and habitual behaviors. This loss of LTD is associated with altered DS-dependent behavior. Given the role of the ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03683-1
更新日期:2018-04-03 00:00:00
abstract::Genetic screens are powerful tools to identify the genes required for a given biological process. However, for technical reasons, comprehensive screens have been restricted to very few model organisms. Therefore, although deep sequencing is revealing the genes of ever more insect species, the functional studies predom...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms8822
更新日期:2015-07-28 00:00:00
abstract::Microalbuminuria is an important clinical marker of several cardiovascular, metabolic, and other diseases such as diabetes, hypertension, atherosclerosis, and cancer. The accurate detection of microalbuminuria relies on albumin quantification in the urine, usually via an immunoturbidity assay; however, like many antib...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11583-1
更新日期:2019-08-09 00:00:00
abstract::The demand for highly scalable, low-power devices for data storage and logic operations is strongly stimulating research into resistive switching as a novel concept for future non-volatile memory devices. To meet technological requirements, it is imperative to have a set of material design rules based on fundamental m...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9610
更新日期:2015-10-19 00:00:00
abstract::Tumor-associated macrophages affect tumor progression and resistance to immune checkpoint therapy. Here, we identify the chemokine signal regulator FROUNT as a target to control tumor-associated macrophages. The low level FROUNT expression in patients with cancer correlates with better clinical outcomes. Frount-defici...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-14338-5
更新日期:2020-01-30 00:00:00
abstract::Large-scale, unbiased proteomics studies are constrained by the complexity of the plasma proteome. Here we report a highly parallel protein quantitation platform integrating nanoparticle (NP) protein coronas with liquid chromatography-mass spectrometry for efficient proteomic profiling. A protein corona is a protein l...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-17033-7
更新日期:2020-07-22 00:00:00
abstract::Human hnRNP A2/B1 is an RNA-binding protein that plays important roles in many biological processes, including maturation, transport, and metabolism of mRNA, and gene regulation of long noncoding RNAs. hnRNP A2/B1 was reported to control the microRNAs sorting to exosomes and promote primary microRNA processing as a po...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02770-z
更新日期:2018-01-29 00:00:00
abstract::A transcriptional programme initiated by the proneural factors Neurog2 and Ascl1 controls successive steps of neurogenesis in the embryonic cerebral cortex. Previous work has shown that proneural factors also confer a migratory behaviour to cortical neurons by inducing the expression of the small GTP-binding proteins ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4405
更新日期:2014-02-27 00:00:00
abstract::CRISPR-Cas immunity is at the forefront of antivirus defense in bacteria and archaea and specifically targets viruses carrying protospacers matching the spacers catalogued in the CRISPR arrays. Here, we perform deep sequencing of the CRISPRome-all spacers contained in a microbiome-associated with hyperthermophilic arc...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-13205-2
更新日期:2019-11-15 00:00:00
abstract::Recent developments in stem cell biology have enabled the study of cell fate decisions in early human development that are impossible to study in vivo. However, understanding how development varies across individuals and, in particular, the influence of common genetic variants during this process has not been characte...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-14457-z
更新日期:2020-02-10 00:00:00
abstract::Mycobacterium tuberculosis (MTB) infects 30% of all humans and kills someone every 20-30 s. Here we report genome-wide binding for ~80% of all predicted MTB transcription factors (TFs), and assayed global expression following induction of each TF. The MTB DNA-binding network consists of ~16,000 binding events from 154...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms6829
更新日期:2015-01-12 00:00:00
abstract::The role of microglia in spinal cord injury (SCI) remains poorly understood and is often confused with the response of macrophages. Here, we use specific transgenic mouse lines and depleting agents to understand the response of microglia after SCI. We find that microglia are highly dynamic and proliferate extensively ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-08446-0
更新日期:2019-01-31 00:00:00
abstract::Alkaline-urea aqueous solvent system provides a novel and important approach for the utilization of polysaccharide. As one of the most important polysaccharide, chitosan can be well dissolved in this solvent system, and the resultant hydrogel material possesses unique and excellent properties. Thus the sound understan...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12033
更新日期:2016-06-23 00:00:00
abstract::Although the chemistry of uranium-ligand multiple bonding is burgeoning, analogous complexes involving other actinides such as thorium remain rare and there are not yet any terminal thorium nitrides outside of cryogenic matrix isolation conditions. Here, we report evidence that reduction of a thorium-azide produces a ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12206-5
更新日期:2019-09-13 00:00:00
abstract::Whole-genome sequencing using sequencing technologies such as Illumina enables the accurate detection of small-scale variants but provides limited information about haplotypes and variants in repetitive regions of the human genome. Single-molecule sequencing (SMS) technologies such as Pacific Biosciences and Oxford Na...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12493-y
更新日期:2019-10-11 00:00:00
abstract::GFI1 is a transcriptional regulator expressed in lymphoid cells, and an "oncorequisite" factor required for development and maintenance of T-lymphoid leukemia. GFI1 deletion causes hypersensitivity to ionizing radiation, for which the molecular mechanism remains unknown. Here, we demonstrate that GFI1 is required in T...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03817-5
更新日期:2018-04-12 00:00:00
abstract::Large reductions in the thermal conductivity of thin silicon membranes have been demonstrated in various porous structures. However, the role of coherent boundary scattering in such structures has become a matter of some debate. Here we report on the first experimental observation of coherent phonon boundary scatterin...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms8228
更新日期:2015-06-24 00:00:00
abstract::Brain oscillations reflect pattern formation of cell assemblies' activity, which is often disturbed in neurological and psychiatric diseases like depression, schizophrenia and stroke. In the neurobiological analysis and treatment of these conditions, transcranial electric currents applied to the brain proved beneficia...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3032
更新日期:2013-01-01 00:00:00
abstract::Several of the steps in protein synthesis on the ribosome utilize hydrolysis of guanosine triphosphate (GTP) as the driving force. This reaction is catalyzed by translation factors that become activated upon binding to the ribosome. The recently determined crystal structure of an elongation factor-Tu ternary complex b...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2741
更新日期:2013-01-01 00:00:00
abstract::In November 2013, a series of earthquakes began along a mapped ancient fault system near Azle, Texas. Here we assess whether it is plausible that human activity caused these earthquakes. Analysis of both lake and groundwater variations near Azle shows that no significant stress changes were associated with the shallow...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms7728
更新日期:2015-04-21 00:00:00
abstract::Intratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and clonal evolution of papillary renal cell carcinoma (pRCC) and rarer kidney cancer subtypes, integrating whole...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16546-5
更新日期:2020-06-18 00:00:00
abstract::Adoptive immunotherapy using chimeric antigen receptor (CAR) expressing T cells targeting the CD19 B lineage receptor has demonstrated marked success in relapsed pre-B-cell acute lymphoblastic leukaemia (ALL). Persisting CAR-T cells generate sustained pressure against CD19 that may drive unique mechanisms of resistanc...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12320
更新日期:2016-07-27 00:00:00
abstract::Neural responses in the cerebral cortex change dramatically between the 'synchronized' state during sleep and 'desynchronized' state during wakefulness. Our understanding of cortical state emerges largely from experiments performed in sensory areas of head-fixed or tethered rodents due to technical limitations of reco...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15803-x
更新日期:2020-04-23 00:00:00
abstract::Physical properties of multi-orbital materials depend not only on the strength of the effective interactions among the valence electrons but also on their type. Strong correlations are caused by either Mott physics that captures the Coulomb repulsion among charges, or Hund physics that aligns the spins in different or...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-10257-2
更新日期:2019-06-20 00:00:00
abstract::Osteoarthritis (OA), primarily characterized by articular cartilage destruction, is the most common form of age-related degenerative whole-joint disease. No disease-modifying treatments for OA are currently available. Although OA is primarily characterized by cartilage destruction, our understanding of the processes c...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-18208-y
更新日期:2020-08-28 00:00:00
abstract::Mitochondrial quality control is essential in highly structured cells such as neurons and muscles. In skeletal muscle the mitochondrial fission proteins are reduced in different physiopathological conditions including ageing sarcopenia, cancer cachexia and chemotherapy-induced muscle wasting. However, whether mitochon...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-10226-9
更新日期:2019-06-12 00:00:00
abstract::Supercooling of aqueous solutions is a fundamentally and practically important physical phenomenon with numerous applications in biopreservation and beyond. Under normal conditions, heterogeneous nucleation mechanisms critically prohibit the simultaneous long-term (> 1 week), large volume (> 1 ml), and low temperature...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-05636-0
更新日期:2018-08-10 00:00:00
abstract::Cell-based therapy exploits modified human cells to treat diseases but its targeted application in specific tissues, particularly those lying deep in the body where direct injection is not possible, has been problematic. Here we use a magnetic resonance imaging (MRI) system to direct macrophages carrying an oncolytic ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9009
更新日期:2015-08-18 00:00:00
abstract::Photovoltaic devices based on metal halide perovskites are rapidly improving in efficiency. Once the Shockley-Queisser limit is reached, charge-carrier extraction will be limited only by radiative bimolecular recombination of electrons with holes. Yet, this fundamental process, and its link with material stoichiometry...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02670-2
更新日期:2018-01-18 00:00:00