当前位置： SCI文献检索 > NATURE GENETICS期刊下所有文献 > Flexible statistical methods for estimating and testing effects in genomic studies with multiple conditions.

Flexible statistical methods for estimating and testing effects in genomic studies with multiple conditions.

Abstract：

:We introduce new statistical methods for analyzing genomic data sets that measure many effects in many conditions (for example, gene expression changes under many treatments). These new methods improve on existing methods by allowing for arbitrary correlations in effect sizes among conditions. This flexible approach increases power, improves effect estimates and allows for more quantitative assessments of effect-size heterogeneity compared to simple shared or condition-specific assessments. We illustrate these features through an analysis of locally acting variants associated with gene expression (cis expression quantitative trait loci (eQTLs)) in 44 human tissues. Our analysis identifies more eQTLs than existing approaches, consistent with improved power. We show that although genetic effects on expression are extensively shared among tissues, effect sizes can still vary greatly among tissues. Some shared eQTLs show stronger effects in subsets of biologically related tissues (for example, brain-related tissues), or in only one tissue (for example, testis). Our methods are widely applicable, computationally tractable for many conditions and available online.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Urbut SM,Wang G,Carbonetto P,Stephens M

doi

10.1038/s41588-018-0268-8

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

187-195

issue

1

eissn

1061-4036

issn

1546-1718

pii

10.1038/s41588-018-0268-8

journal_volume

51

pub_type

杂志文章

相关文献

NATURE GENETICS文献大全
  • Urocortin-deficient mice show hearing impairment and increased anxiety-like behavior.

    abstract：:Urocortin is a member of the corticotropin-releasing hormone peptide family and is found in many discrete brain regions. The distinct expression pattern of urocortin suggests that it influences such behaviors as feeding, anxiety and auditory processing. To better define the physiological roles of urocortin, we have ge...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng914

    authors： Vetter DE,Li C,Zhao L,Contarino A,Liberman MC,Smith GW,Marchuk Y,Koob GF,Heinemann SF,Vale W,Lee KF

    更新日期：2002-08-01 00:00:00

  • Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer.

    abstract：:Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,10...

    journal_title：Nature genetics

    pub_type： 杂志文章,多中心研究

    doi：10.1038/s41588-020-0636-z

    authors： Lee HO,Hong Y,Etlioglu HE,Cho YB,Pomella V,Van den Bosch B,Vanhecke J,Verbandt S,Hong H,Min JW,Kim N,Eum HH,Qian J,Boeckx B,Lambrechts D,Tsantoulis P,De Hertogh G,Chung W,Lee T,An M,Shin HT,Joung JG,Jung MH,

    更新日期：2020-06-01 00:00:00

  • Assessing the impact of population stratification on genetic association studies.

    abstract：:Population stratification refers to differences in allele frequencies between cases and controls due to systematic differences in ancestry rather than association of genes with disease. It has been proposed that false positive associations due to stratification can be controlled by genotyping a few dozen unlinked gene...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1333

    authors： Freedman ML,Reich D,Penney KL,McDonald GJ,Mignault AA,Patterson N,Gabriel SB,Topol EJ,Smoller JW,Pato CN,Pato MT,Petryshen TL,Kolonel LN,Lander ES,Sklar P,Henderson B,Hirschhorn JN,Altshuler D

    更新日期：2004-04-01 00:00:00

  • Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma.

    abstract：:Glaucoma is the leading cause of irreversible blindness globally 1 . Despite its gravity, the disease is frequently undiagnosed in the community 2 . Raised intraocular pressure (IOP) is the most important risk factor for primary open-angle glaucoma (POAG)3,4. Here we present a meta-analysis of 139,555 European partici...

    journal_title：Nature genetics

    pub_type： 杂志文章,meta分析

    doi：10.1038/s41588-018-0126-8

    authors： Khawaja AP,Cooke Bailey JN,Wareham NJ,Scott RA,Simcoe M,Igo RP Jr,Song YE,Wojciechowski R,Cheng CY,Khaw PT,Pasquale LR,Haines JL,Foster PJ,Wiggs JL,Hammond CJ,Hysi PG,UK Biobank Eye and Vision Consortium.,NEIGHBORHOOD C

    更新日期：2018-06-01 00:00:00

  • Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia.

    abstract：:The past decade has seen great advances in unraveling the biological basis of hereditary ataxias. Molecular studies of spinocerebellar ataxias (SCA) have extended our understanding of dominant ataxias. Causative genes have been identified for a few autosomal recessive ataxias: Friedreich's ataxia, ataxia with vitamin ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1927

    authors： Gros-Louis F,Dupré N,Dion P,Fox MA,Laurent S,Verreault S,Sanes JR,Bouchard JP,Rouleau GA

    更新日期：2007-01-01 00:00:00

  • A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma.

    abstract：:The molecular mechanisms underlying angioimmunoblastic T cell lymphoma (AITL), a common type of mature T cell lymphoma of poor prognosis, are largely unknown. Here we report a frequent somatic mutation in RHOA (encoding p.Gly17Val) using exome and transcriptome sequencing of samples from individuals with AITL. Further...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2916

    authors： Yoo HY,Sung MK,Lee SH,Kim S,Lee H,Park S,Kim SC,Lee B,Rho K,Lee JE,Cho KH,Kim W,Ju H,Kim J,Kim SJ,Kim WS,Lee S,Ko YH

    更新日期：2014-04-01 00:00:00

  • R-spondin1 is essential in sex determination, skin differentiation and malignancy.

    abstract：:R-spondins are a recently characterized small family of growth factors. Here we show that human R-spondin1 (RSPO1) is the gene disrupted in a recessive syndrome characterized by XX sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. Our data show, for the first time, th...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1907

    authors： Parma P,Radi O,Vidal V,Chaboissier MC,Dellambra E,Valentini S,Guerra L,Schedl A,Camerino G

    更新日期：2006-11-01 00:00:00

  • The human PAX6 gene is mutated in two patients with aniridia.

    abstract：:Aniridia is an inherited ocular disorder of variable expressivity characterized by iris hypoplasia. A candidate aniridia gene, AN, which is the human homologue of the mouse Pax-6 gene, has recently been isolated by positional cloning from the WAGR region of 11p13. Here we describe mutations in this gene in two cases o...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0892-328

    authors： Jordan T,Hanson I,Zaletayev D,Hodgson S,Prosser J,Seawright A,Hastie N,van Heyningen V

    更新日期：1992-08-01 00:00:00

  • Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1.

    abstract：:Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by expansion of a polyglutamine tract in ataxin-1. In affected neurons of SCA1 patients and transgenic mice, mutant ataxin-1 accumulates in a single, ubiquitin-positive nuclear inclusion. In this study, we show that these i...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/502

    authors： Cummings CJ,Mancini MA,Antalffy B,DeFranco DB,Orr HT,Zoghbi HY

    更新日期：1998-06-01 00:00:00

  • Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia.

    abstract：:Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females. We sequenced genes in this region and found heterozygous and ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng2057

    authors： Wang X,Reid Sutton V,Omar Peraza-Llanes J,Yu Z,Rosetta R,Kou YC,Eble TN,Patel A,Thaller C,Fang P,Van den Veyver IB

    更新日期：2007-07-01 00:00:00

  • A double-stranded RNA binding protein required for activation of repressed messages in mammalian germ cells.

    abstract：:Chromatin packaging in mammalian spermatozoa requires an ordered replacement of the somatic histones by two classes of spermatid-specific basic proteins, the transition proteins and the protamines. Temporal expression of transition proteins and protamines during spermatid differentiation is under translational control...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/9684

    authors： Zhong J,Peters AH,Lee K,Braun RE

    更新日期：1999-06-01 00:00:00

  • Genome-wide association study identifies a common variant associated with risk of endometrial cancer.

    abstract：:Endometrial cancer is the most common malignancy of the female genital tract in developed countries. To identify genetic variants associated with endometrial cancer risk, we performed a genome-wide association study involving 1,265 individuals with endometrial cancer (cases) from Australia and the UK and 5,190 control...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.812

    authors： Spurdle AB,Thompson DJ,Ahmed S,Ferguson K,Healey CS,O'Mara T,Walker LC,Montgomery SB,Dermitzakis ET,Australian National Endometrial Cancer Study Group.,Fahey P,Montgomery GW,Webb PM,Fasching PA,Beckmann MW,Ekici AB,Hein A

    更新日期：2011-05-01 00:00:00

  • Systematic assessment of copy number variant detection via genome-wide SNP genotyping.

    abstract：:SNP genotyping has emerged as a technology to incorporate copy number variants (CNVs) into genetic analyses of human traits. However, the extent to which SNP platforms accurately capture CNVs remains unclear. Using independent, sequence-based CNV maps, we find that commonly used SNP platforms have limited or no probe ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.236

    authors： Cooper GM,Zerr T,Kidd JM,Eichler EE,Nickerson DA

    更新日期：2008-10-01 00:00:00

  • Mutations in RNF135, a gene within the NF1 microdeletion region, cause phenotypic abnormalities including overgrowth.

    abstract：:17q11 microdeletions that encompass NF1 cause 5%-10% of cases of neurofibromatosis type 1, and individuals with microdeletions are typically taller than individuals with intragenic NF1 mutations, suggesting that deletion of a neighboring gene might promote human growth. We identified mutations in RNF135, which is with...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng2083

    authors： Douglas J,Cilliers D,Coleman K,Tatton-Brown K,Barker K,Bernhard B,Burn J,Huson S,Josifova D,Lacombe D,Malik M,Mansour S,Reid E,Cormier-Daire V,Cole T,Childhood Overgrowth Collaboration.,Rahman N

    更新日期：2007-08-01 00:00:00

  • Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA).

    abstract：:Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurologic disorder characterized by variable combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis and dementia. By specifically searching published brain cDNA sequences for the presence of CAG repeats we identified uns...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0194-9

    authors： Koide R,Ikeuchi T,Onodera O,Tanaka H,Igarashi S,Endo K,Takahashi H,Kondo R,Ishikawa A,Hayashi T

    更新日期：1994-01-01 00:00:00

  • Accelerated genetic drift on chromosome X during the human dispersal out of Africa.

    abstract：:Comparisons of chromosome X and the autosomes can illuminate differences in the histories of males and females as well as shed light on the forces of natural selection. We compared the patterns of variation in these parts of the genome using two datasets that we assembled for this study that are both genomic in scale....

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.303

    authors： Keinan A,Mullikin JC,Patterson N,Reich D

    更新日期：2009-01-01 00:00:00

  • In vivo selection using a cell-growth switch.

    abstract：:A major obstacle to stem-cell gene therapy rests in the inability to deliver a gene into a therapeutically relevant fraction of stem cells. One way to circumvent this obstacle is to use selection. Vectors containing two linked genes serve as the basis for selection, with one gene encoding a selectable product and the ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/79194

    authors： Jin L,Zeng H,Chien S,Otto KG,Richard RE,Emery DW,Blau CA

    更新日期：2000-09-01 00:00:00

  • Soluble epoxide hydrolase is a susceptibility factor for heart failure in a rat model of human disease.

    abstract：:We aimed to identify genetic variants associated with heart failure by using a rat model of the human disease. We performed invasive cardiac hemodynamic measurements in F2 crosses between spontaneously hypertensive heart failure (SHHF) rats and reference strains. We combined linkage analyses with genome-wide expressio...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.129

    authors： Monti J,Fischer J,Paskas S,Heinig M,Schulz H,Gösele C,Heuser A,Fischer R,Schmidt C,Schirdewan A,Gross V,Hummel O,Maatz H,Patone G,Saar K,Vingron M,Weldon SM,Lindpaintner K,Hammock BD,Rohde K,Dietz R,Cook SA,Sc

    更新日期：2008-05-01 00:00:00

  • Early TP53 alterations engage environmental exposures to promote gastric premalignancy in an integrative mouse model.

    abstract：:Somatic alterations in cancer genes are being detected in normal and premalignant tissue, thus placing greater emphasis on gene-environment interactions that enable disease phenotypes. By combining early genetic alterations with disease-relevant exposures, we developed an integrative mouse model to study gastric prema...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-019-0574-9

    authors： Sethi NS,Kikuchi O,Duronio GN,Stachler MD,McFarland JM,Ferrer-Luna R,Zhang Y,Bao C,Bronson R,Patil D,Sanchez-Vega F,Liu JB,Sicinska E,Lazaro JB,Ligon KL,Beroukhim R,Bass AJ

    更新日期：2020-02-01 00:00:00

  • Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2.

    abstract：:Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR-Cas9-mediated forward genetic screen, we identified MORC2 as an essential gene required for epigenetic silencing b...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3878

    authors： Tchasovnikarova IA,Timms RT,Douse CH,Roberts RC,Dougan G,Kingston RE,Modis Y,Lehner PJ

    更新日期：2017-07-01 00:00:00

  • Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors.

    abstract：:Tumor mutational burden correlates with response to immune checkpoint blockade in multiple solid tumors, although in microsatellite-stable tumors this association is of uncertain clinical utility. Here we uniformly analyzed whole-exome sequencing (WES) of 249 tumors and matched normal tissue from patients with clinica...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-018-0200-2

    authors： Miao D,Margolis CA,Vokes NI,Liu D,Taylor-Weiner A,Wankowicz SM,Adeegbe D,Keliher D,Schilling B,Tracy A,Manos M,Chau NG,Hanna GJ,Polak P,Rodig SJ,Signoretti S,Sholl LM,Engelman JA,Getz G,Jänne PA,Haddad RI,Chouei

    更新日期：2018-09-01 00:00:00

  • Multiple knockout analysis of genetic robustness in the yeast metabolic network.

    abstract：:Genetic robustness characterizes the constancy of the phenotype in face of heritable perturbations. Previous investigations have used comprehensive single and double gene knockouts to study gene essentiality and pairwise gene interactions in the yeast Saccharomyces cerevisiae. Here we conduct an in silico multiple kno...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1856

    authors： Deutscher D,Meilijson I,Kupiec M,Ruppin E

    更新日期：2006-09-01 00:00:00

  • Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53.

    abstract：:The p53 protein can inhibit cell cycling or induce apoptosis, and is thus a critical regulator of tumorigenesis. This protein is negatively regulated by a physical interaction with MDM2, an E3 ubiquitin ligase. This interaction is critical for cell viability; loss of Mdm2 causes cell death in vitro and in vivo in a p5...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng714

    authors： Parant J,Chavez-Reyes A,Little NA,Yan W,Reinke V,Jochemsen AG,Lozano G

    更新日期：2001-09-01 00:00:00

  • The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease.

    abstract：:The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1943

    authors： Rogaeva E,Meng Y,Lee JH,Gu Y,Kawarai T,Zou F,Katayama T,Baldwin CT,Cheng R,Hasegawa H,Chen F,Shibata N,Lunetta KL,Pardossi-Piquard R,Bohm C,Wakutani Y,Cupples LA,Cuenco KT,Green RC,Pinessi L,Rainero I,Sorbi S,

    更新日期：2007-02-01 00:00:00

  • Y chromosome sequence variation and the history of human populations.

    abstract：:Binary polymorphisms associated with the non-recombining region of the human Y chromosome (NRY) preserve the paternal genetic legacy of our species that has persisted to the present, permitting inference of human evolution, population affinity and demographic history. We used denaturing high-performance liquid chromat...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/81685

    authors： Underhill PA,Shen P,Lin AA,Jin L,Passarino G,Yang WH,Kauffman E,Bonné-Tamir B,Bertranpetit J,Francalacci P,Ibrahim M,Jenkins T,Kidd JR,Mehdi SQ,Seielstad MT,Wells RS,Piazza A,Davis RW,Feldman MW,Cavalli-Sforza LL,

    更新日期：2000-11-01 00:00:00

  • Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis.

    abstract：:Animal models indicate that the antimicrobial peptide hepcidin (HAMP; OMIM 606464) is probably a key regulator of iron absorption in mammals. Here we report the identification of two mutations (93delG and 166C-->T) in HAMP on 19q13 in two families with a new type of juvenile hemochromatosis. ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1053

    authors： Roetto A,Papanikolaou G,Politou M,Alberti F,Girelli D,Christakis J,Loukopoulos D,Camaschella C

    更新日期：2003-01-01 00:00:00

  • Identification and characterization of rod-derived cone viability factor.

    abstract：:Retinitis pigmentosa is an untreatable, inherited retinal disease that leads to blindness. The disease initiates with the loss of night vision due to rod photoreceptor degeneration, followed by irreversible, progressive loss of cone photoreceptor. Cone loss is responsible for the main visual handicap, as cones are ess...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1386

    authors： Léveillard T,Mohand-Saïd S,Lorentz O,Hicks D,Fintz AC,Clérin E,Simonutti M,Forster V,Cavusoglu N,Chalmel F,Dollé P,Poch O,Lambrou G,Sahel JA

    更新日期：2004-07-01 00:00:00

  • Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs.

    abstract：:Schizophrenia is a complex disorder caused by both genetic and environmental factors. Using 9,087 affected individuals, 12,171 controls and 915,354 imputed SNPs from the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC-SCZ), we estimate that 23% (s.e. = 1%) of variation in liability to sc...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.1108

    authors： Lee SH,DeCandia TR,Ripke S,Yang J,Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ).,International Schizophrenia Consortium (ISC).,Molecular Genetics of Schizophrenia Collaboration (MGS).,Sullivan PF,Goddard ME

    更新日期：2012-02-19 00:00:00

  • Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning.

    abstract：:1 alpha,25-Dihydroxyvitamin D3[1 alpha,25(OH)2D3], an active form of vitamin D, has roles in many biological phenomena such as calcium homeostasis and bone formation, which are thought to be mediated by the 1 alpha,25(OH)2D3 receptor (VDR), a member of the nuclear hormone receptor superfamily. However, the molecular b...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0897-391

    authors： Yoshizawa T,Handa Y,Uematsu Y,Takeda S,Sekine K,Yoshihara Y,Kawakami T,Arioka K,Sato H,Uchiyama Y,Masushige S,Fukamizu A,Matsumoto T,Kato S

    更新日期：1997-08-01 00:00:00

  • Probabilistic fine-mapping of transcriptome-wide association studies.

    abstract：:Transcriptome-wide association studies using predicted expression have identified thousands of genes whose locally regulated expression is associated with complex traits and diseases. In this work, we show that linkage disequilibrium induces significant gene-trait associations at non-causal genes as a function of the ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-019-0367-1

    authors： Mancuso N,Freund MK,Johnson R,Shi H,Kichaev G,Gusev A,Pasaniuc B

    更新日期：2019-04-01 00:00:00