Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics.

Abstract:

:Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression to compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy and general robustness to misspecified reference sets. We apply this framework to 44 GTEx tissues and 100+ phenotypes from GWAS and meta-analysis studies, creating a growing public catalog of associations that seeks to capture the effects of gene expression variation on human phenotypes. Replication in an independent cohort is shown. Most of the associations are tissue specific, suggesting context specificity of the trait etiology. Colocalized significant associations in unexpected tissues underscore the need for an agnostic scanning of multiple contexts to improve our ability to detect causal regulatory mechanisms. Monogenic disease genes are enriched among significant associations for related traits, suggesting that smaller alterations of these genes may cause a spectrum of milder phenotypes.

journal_name

Nat Commun

journal_title

Nature communications

authors

Barbeira AN,Dickinson SP,Bonazzola R,Zheng J,Wheeler HE,Torres JM,Torstenson ES,Shah KP,Garcia T,Edwards TL,Stahl EA,Huckins LM,GTEx Consortium.,Nicolae DL,Cox NJ,Im HK

doi

10.1038/s41467-018-03621-1

subject

Has Abstract

pub_date

2018-05-08 00:00:00

pages

1825

issue

1

issn

2041-1723

pii

10.1038/s41467-018-03621-1

journal_volume

9

pub_type

杂志文章
  • Fluidity onset in graphene.

    abstract::Viscous electron fluids have emerged recently as a new paradigm of strongly-correlated electron transport in solids. Here we report on a direct observation of the transition to this long-sought-for state of matter in a high-mobility electron system in graphene. Unexpectedly, the electron flow is found to be interactio...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07004-4

    authors: Bandurin DA,Shytov AV,Levitov LS,Kumar RK,Berdyugin AI,Ben Shalom M,Grigorieva IV,Geim AK,Falkovich G

    更新日期:2018-10-31 00:00:00

  • 14-3-3 proteins regulate Tctp-Rheb interaction for organ growth in Drosophila.

    abstract::14-3-3 family proteins regulate multiple signalling pathways. Understanding biological functions of 14-3-3 proteins has been limited by the functional redundancy of conserved isotypes. Here we provide evidence that 14-3-3 proteins regulate two interacting components of Tor signalling in Drosophila, translationally con...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms11501

    authors: Le TP,Vuong LT,Kim AR,Hsu YC,Choi KW

    更新日期:2016-05-06 00:00:00

  • Complex formation of APP with GABAB receptors links axonal trafficking to amyloidogenic processing.

    abstract::GABAB receptors (GBRs) are key regulators of synaptic release but little is known about trafficking mechanisms that control their presynaptic abundance. We now show that sequence-related epitopes in APP, AJAP-1 and PIANP bind with nanomolar affinities to the N-terminal sushi-domain of presynaptic GBRs. Of the three in...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-09164-3

    authors: Dinamarca MC,Raveh A,Schneider A,Fritzius T,Früh S,Rem PD,Stawarski M,Lalanne T,Turecek R,Choo M,Besseyrias V,Bildl W,Bentrop D,Staufenbiel M,Gassmann M,Fakler B,Schwenk J,Bettler B

    更新日期:2019-03-22 00:00:00

  • Global chromatin conformation differences in the Drosophila dosage compensated chromosome X.

    abstract::In Drosophila melanogaster the single male chromosome X undergoes an average twofold transcriptional upregulation for balancing the transcriptional output between sexes. Previous literature hypothesised that a global change in chromosome structure may accompany this process. However, recent studies based on Hi-C faile...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-13350-8

    authors: Pal K,Forcato M,Jost D,Sexton T,Vaillant C,Salviato E,Mazza EMC,Lugli E,Cavalli G,Ferrari F

    更新日期:2019-11-25 00:00:00

  • HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients.

    abstract::Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder due to selective loss of motor neurons (MNs). Mutations in the fused in sarcoma (FUS) gene can cause both juvenile and late onset ALS. We generated and characterized induced pluripotent stem cells (iPSCs) from ALS patients with dif...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-00911-y

    authors: Guo W,Naujock M,Fumagalli L,Vandoorne T,Baatsen P,Boon R,Ordovás L,Patel A,Welters M,Vanwelden T,Geens N,Tricot T,Benoy V,Steyaert J,Lefebvre-Omar C,Boesmans W,Jarpe M,Sterneckert J,Wegner F,Petri S,Bohl D,Vande

    更新日期:2017-10-11 00:00:00

  • Potential regime shift in decreased sea ice production after the Mertz Glacier calving.

    abstract::Variability in dense shelf water formation can potentially impact Antarctic Bottom Water (AABW) production, a vital component of the global climate system. In East Antarctica, the George V Land polynya system (142-150°E) is structured by the local 'icescape', promoting sea ice formation that is driven by the offshore ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms1820

    authors: Tamura T,Williams GD,Fraser AD,Ohshima KI

    更新日期:2012-05-08 00:00:00

  • A majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation.

    abstract::Antiretroviral therapy (ART) suppresses viral replication in people living with HIV. Yet, infected cells persist for decades on ART and viremia returns if ART is stopped. Persistence has been attributed to viral replication in an ART sanctuary and long-lived and/or proliferating latently infected cells. Using ecologic...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-06843-5

    authors: Reeves DB,Duke ER,Wagner TA,Palmer SE,Spivak AM,Schiffer JT

    更新日期:2018-11-16 00:00:00

  • Olfactory specificity regulates lipid metabolism through neuroendocrine signaling in Caenorhabditis elegans.

    abstract::Olfactory and metabolic dysfunctions are intertwined phenomena associated with obesity and neurodegenerative diseases; yet how mechanistically olfaction regulates metabolic homeostasis remains unclear. Specificity of olfactory perception integrates diverse environmental odors and olfactory neurons expressing different...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-15296-8

    authors: Mutlu AS,Gao SM,Zhang H,Wang MC

    更新日期:2020-03-19 00:00:00

  • Photonic integrated field-programmable disk array signal processor.

    abstract::Thanks to the nature of strong programmability, field-programmable gate arrays (FPGAs) have been playing a significant role in signal processing and control. With the explosive growth in digital data, big data analytics becomes an important emerging field, in which FPGAs are a major player. However, the computational ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-14249-0

    authors: Zhang W,Yao J

    更新日期:2020-01-21 00:00:00

  • Recent strengthening of the stratospheric Arctic vortex response to warming in the central North Pacific.

    abstract::The stratospheric Arctic vortex (SAV) plays a critical role in forecasting cold winters in northern mid-latitudes. Its influence on the tropospheric mid- and high-latitudes has attracted growing attention in recent years. However, the trend in the SAV during the recent two decades is still unknown. Here, using three r...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-04138-3

    authors: Hu D,Guan Z,Tian W,Ren R

    更新日期:2018-04-27 00:00:00

  • Resident c-kit(+) cells in the heart are not cardiac stem cells.

    abstract::Identifying a bona fide population of cardiac stem cells (CSCs) is a critical step for developing cell-based therapies for heart failure patients. Previously, cardiac c-kit(+) cells were reported to be CSCs with a potential to become myocardial, endothelial and smooth muscle cells in vitro and after cardiac injury. He...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms9701

    authors: Sultana N,Zhang L,Yan J,Chen J,Cai W,Razzaque S,Jeong D,Sheng W,Bu L,Xu M,Huang GY,Hajjar RJ,Zhou B,Moon A,Cai CL

    更新日期:2015-10-30 00:00:00

  • Benchmarking monolayer MoS2 and WS2 field-effect transistors.

    abstract::Here we benchmark device-to-device variation in field-effect transistors (FETs) based on monolayer MoS2 and WS2 films grown using metal-organic chemical vapor deposition process. Our study involves 230 MoS2 FETs and 160 WS2 FETs with channel lengths ranging from 5 μm down to 100 nm. We use statistical measures to eval...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-20732-w

    authors: Sebastian A,Pendurthi R,Choudhury TH,Redwing JM,Das S

    更新日期:2021-01-29 00:00:00

  • Outlines of the pore in open and closed conformations describe the gating mechanism of ASIC1.

    abstract::The proton-activated sodium channel ASIC1 belongs to the ENaC/Degenerins family of ion channels. Little is known about gating of the pore in any member of this class. Here we outline the shape of the ion pathway of ASIC1 in the open and closed conformations by measuring apparent rates of cysteine modification by thiol...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms1409

    authors: Li T,Yang Y,Canessa CM

    更新日期:2011-07-19 00:00:00

  • Increased prevalence of EPAS1 variant in cattle with high-altitude pulmonary hypertension.

    abstract::High-altitude pulmonary hypertension (HAPH) has heritable features and is a major cause of death in cattle in the Rocky Mountains, USA. Although multiple genes are likely involved in the genesis of HAPH, to date no major gene variant has been identified. Using whole-exome sequencing, we report the high association of ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7863

    authors: Newman JH,Holt TN,Cogan JD,Womack B,Phillips JA 3rd,Li C,Kendall Z,Stenmark KR,Thomas MG,Brown RD,Riddle SR,West JD,Hamid R

    更新日期:2015-04-15 00:00:00

  • Oxide-ion conduction in the Dion-Jacobson phase CsBi2Ti2NbO10-δ.

    abstract::Oxide-ion conductors have found applications in various electrochemical devices, such as solid-oxide fuel cells, gas sensors, and separation membranes. Dion-Jacobson phases are known for their rich magnetic and electrical properties; however, there have been no reports on oxide-ion conduction in this family of materia...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-15043-z

    authors: Zhang W,Fujii K,Niwa E,Hagihala M,Kamiyama T,Yashima M

    更新日期:2020-03-06 00:00:00

  • Abnormal degradation of the neuronal stress-protective transcription factor HSF1 in Huntington's disease.

    abstract::Huntington's Disease (HD) is a neurodegenerative disease caused by poly-glutamine expansion in the Htt protein, resulting in Htt misfolding and cell death. Expression of the cellular protein folding and pro-survival machinery by heat shock transcription factor 1 (HSF1) ameliorates biochemical and neurobiological defec...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms14405

    authors: Gomez-Pastor R,Burchfiel ET,Neef DW,Jaeger AM,Cabiscol E,McKinstry SU,Doss A,Aballay A,Lo DC,Akimov SS,Ross CA,Eroglu C,Thiele DJ

    更新日期:2017-02-13 00:00:00

  • Embedding laser generated nanocrystals in BiVO4 photoanode for efficient photoelectrochemical water splitting.

    abstract::Addressing the intrinsic charge transport limitation of metal oxides has been of significance for pursuing viable PEC water splitting photoelectrodes. Growing a photoelectrode with conductive nanoobjects embedded in the matrix is promising for enhanced charge transport but remains a challenge technically. We herein sh...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-10543-z

    authors: Jian J,Xu Y,Yang X,Liu W,Fu M,Yu H,Xu F,Feng F,Jia L,Friedrich D,van de Krol R,Wang H

    更新日期:2019-06-13 00:00:00

  • Discovery of protein acetylation patterns by deconvolution of peptide isomer mass spectra.

    abstract::Protein post-translational modifications (PTMs) play important roles in the control of various biological processes including protein-protein interactions, epigenetics and cell cycle regulation. Mass spectrometry-based proteomics approaches enable comprehensive identification and quantitation of numerous types of PTMs...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms9648

    authors: Abshiru N,Caron-Lizotte O,Rajan RE,Jamai A,Pomies C,Verreault A,Thibault P

    更新日期:2015-10-15 00:00:00

  • Publisher Correction: Control of laser plasma accelerated electrons for light sources.

    abstract::The original version of this Article contained an error in the last sentence of the first paragraph of the Introduction and incorrectly read 'A proper electron beam control is one of the main challenges towards the Graal of developing a compact alternative of X-ray free-electron lasers by coupling LWFA gigaelectron-vo...

    journal_title:Nature communications

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41467-018-04299-1

    authors: André T,Andriyash IA,Loulergue A,Labat M,Roussel E,Ghaith A,Khojoyan M,Thaury C,Valléau M,Briquez F,Marteau F,Tavakoli K,N'Gotta P,Dietrich Y,Lambert G,Malka V,Benabderrahmane C,Vétéran J,Chapuis L,El Ajjouri T,Se

    更新日期:2018-05-02 00:00:00

  • The landscape of viral expression and host gene fusion and adaptation in human cancer.

    abstract::Viruses cause 10-15% of all human cancers. Massively parallel sequencing has recently proved effective for uncovering novel viruses and virus-tumour associations, but this approach has not yet been applied to comprehensive patient cohorts. Here we screen a diverse landscape of human cancer, encompassing 4,433 tumours ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms3513

    authors: Tang KW,Alaei-Mahabadi B,Samuelsson T,Lindh M,Larsson E

    更新日期:2013-01-01 00:00:00

  • A machine learning-based chemoproteomic approach to identify drug targets and binding sites in complex proteomes.

    abstract::Chemoproteomics is a key technology to characterize the mode of action of drugs, as it directly identifies the protein targets of bioactive compounds and aids in the development of optimized small-molecule compounds. Current approaches cannot identify the protein targets of a compound and also detect the interaction s...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-18071-x

    authors: Piazza I,Beaton N,Bruderer R,Knobloch T,Barbisan C,Chandat L,Sudau A,Siepe I,Rinner O,de Souza N,Picotti P,Reiter L

    更新日期:2020-08-21 00:00:00

  • Photobactericidal activity activated by thiolated gold nanoclusters at low flux levels of white light.

    abstract::The emergence of antibiotic resistant bacteria is a major threat to the practice of modern medicine. Photobactericidal agents have obtained significant attention as promising candidates to kill bacteria, and they have been extensively studied. However, to obtain photobactericidal activity, an intense white light sourc...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-15004-6

    authors: Hwang GB,Huang H,Wu G,Shin J,Kafizas A,Karu K,Toit HD,Alotaibi AM,Mohammad-Hadi L,Allan E,MacRobert AJ,Gavriilidis A,Parkin IP

    更新日期:2020-03-05 00:00:00

  • DNA replication licensing factor Cdc6 and Plk4 kinase antagonistically regulate centrosome duplication via Sas-6.

    abstract::Centrosome number is tightly controlled during the cell cycle to ensure proper spindle assembly and cell division. However, the underlying mechanism that controls centrosome number remains largely unclear. We show herein that the DNA replication licensing factor Cdc6 is recruited to the proximal side of the centrioles...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms15164

    authors: Xu X,Huang S,Zhang B,Huang F,Chi W,Fu J,Wang G,Li S,Jiang Q,Zhang C

    更新日期:2017-04-27 00:00:00

  • Reciprocal regulation of the Il9 locus by counteracting activities of transcription factors IRF1 and IRF4.

    abstract::The T helper 9 (Th9) cell transcriptional network is formed by an equilibrium of signals induced by cytokines and antigen presentation. Here we show that, within this network, two interferon regulatory factors (IRF), IRF1 and IRF4, display opposing effects on Th9 differentiation. IRF4 dose-dependently promotes, wherea...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms15366

    authors: Campos Carrascosa L,Klein M,Kitagawa Y,Lückel C,Marini F,König A,Guralnik A,Raifer H,Hagner-Benes S,Rädler D,Böck A,Kang C,Lohoff M,Garn H,Schaub B,Berberich-Siebelt F,Sakaguchi S,Bopp T,Huber M

    更新日期:2017-05-12 00:00:00

  • Urban areas as hotspots for bees and pollination but not a panacea for all insects.

    abstract::Urbanisation is an important global driver of biodiversity change, negatively impacting some species groups whilst providing opportunities for others. Yet its impact on ecosystem services is poorly investigated. Here, using a replicated experimental design, we test how Central European cities impact flying insects and...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-14496-6

    authors: Theodorou P,Radzevičiūtė R,Lentendu G,Kahnt B,Husemann M,Bleidorn C,Settele J,Schweiger O,Grosse I,Wubet T,Murray TE,Paxton RJ

    更新日期:2020-01-29 00:00:00

  • A pairwise maximum entropy model accurately describes resting-state human brain networks.

    abstract::The resting-state human brain networks underlie fundamental cognitive functions and consist of complex interactions among brain regions. However, the level of complexity of the resting-state networks has not been quantified, which has prevented comprehensive descriptions of the brain activity as an integrative system....

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms2388

    authors: Watanabe T,Hirose S,Wada H,Imai Y,Machida T,Shirouzu I,Konishi S,Miyashita Y,Masuda N

    更新日期:2013-01-01 00:00:00

  • An asymmetric heterodomain interface stabilizes a response regulator-DNA complex.

    abstract::Two-component signal transduction systems consist of pairs of histidine kinases and response regulators, which mediate adaptive responses to environmental cues. Most activated response regulators regulate transcription by binding tightly to promoter DNA via a phosphorylation-triggered inactive-to-active transition. Th...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms4282

    authors: Narayanan A,Kumar S,Evrard AN,Paul LN,Yernool DA

    更新日期:2014-01-01 00:00:00

  • Total synthesis of teixobactin.

    abstract::To cope with the global bacterial multidrug resistance, scientific communities have devoted significant efforts to develop novel antibiotics, particularly those with new modes of actions. Teixobactin, recently isolated from uncultured bacteria, is considered as a promising first-in-class drug candidate for clinical de...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms12394

    authors: Jin K,Sam IH,Po KHL,Lin D,Ghazvini Zadeh EH,Chen S,Yuan Y,Li X

    更新日期:2016-08-03 00:00:00

  • Stripe-like nanoscale structural phase separation in superconducting BaPb(1-x)Bi(x)O3.

    abstract::The phase diagram of BaPb(1-x)Bi(x)O3 exhibits a superconducting dome in the proximity of a charge density wave phase. For the superconducting compositions, the material coexists as two structural polymorphs. Here we show, via high-resolution transmission electron microscopy, that the structural dimorphism is accommod...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms9231

    authors: Giraldo-Gallo P,Zhang Y,Parra C,Manoharan HC,Beasley MR,Geballe TH,Kramer MJ,Fisher IR

    更新日期:2015-09-16 00:00:00

  • Publisher Correction: The mutational impact of culturing human pluripotent and adult stem cells.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature communications

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41467-020-17797-y

    authors: Kuijk E,Jager M,van der Roest B,Locati MD,Van Hoeck A,Korzelius J,Janssen R,Besselink N,Boymans S,van Boxtel R,Cuppen E

    更新日期:2020-08-04 00:00:00