当前位置： SCI文献检索 > NATURE GENETICS期刊下所有文献 > Meta-analysis of gene-level tests for rare variant association.

Meta-analysis of gene-level tests for rare variant association.

Abstract：

:The majority of reported complex disease associations for common genetic variants have been identified through meta-analysis, a powerful approach that enables the use of large sample sizes while protecting against common artifacts due to population structure and repeated small-sample analyses sharing individual-level data. As the focus of genetic association studies shifts to rare variants, genes and other functional units are becoming the focus of analysis. Here we propose and evaluate new approaches for performing meta-analysis of rare variant association tests, including burden tests, weighted burden tests, variable-threshold tests and tests that allow variants with opposite effects to be grouped together. We show that our approach retains useful features from single-variant meta-analysis approaches and demonstrate its use in a study of blood lipid levels in ∼18,500 individuals genotyped with exome arrays.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Liu DJ,Peloso GM,Zhan X,Holmen OL,Zawistowski M,Feng S,Nikpay M,Auer PL,Goel A,Zhang H,Peters U,Farrall M,Orho-Melander M,Kooperberg C,McPherson R,Watkins H,Willer CJ,Hveem K,Melander O,Kathiresan S,Abecasis GR

doi

10.1038/ng.2852

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

200-4

issue

2

eissn

1061-4036

issn

1546-1718

pii

ng.2852

journal_volume

46

pub_type

杂志文章,meta分析

相关文献

NATURE GENETICS文献大全
  • Iron on the brain.

    abstract：:Accumulations of iron are often detected in the brains of people suffering from neurodegenerative diseases. But it is often not known whether such accumulations contribute directly to disease progression. The identification of the genes mutated in two such disorders suggests that errors in iron metabolism do indeed ha...

    journal_title：Nature genetics

    pub_type： 评论,新闻

    doi：10.1038/91036

    authors： Rouault TA

    更新日期：2001-08-01 00:00:00

  • SGS1, the Saccharomyces cerevisiae homologue of BLM and WRN, suppresses genome instability and homeologous recombination.

    abstract：:The Escherichia coli gene recQ was identified as a RecF recombination pathway gene. The gene SGS1, encoding the only RecQ-like DNA helicase in Saccharomyces cerevisiae, was identified by mutations that suppress the top3 slow-growth phenotype. Relatively little is known about the function of Sgs1p because single mutati...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/83673

    authors： Myung K,Datta A,Chen C,Kolodner RD

    更新日期：2001-01-01 00:00:00

  • Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer.

    abstract：:Many genes associated with CpG islands undergo de novo methylation in cancer. Studies have suggested that the pattern of this modification may be partially determined by an instructive mechanism that recognizes specifically marked regions of the genome. Using chromatin immunoprecipitation analysis, here we show that g...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1950

    authors： Schlesinger Y,Straussman R,Keshet I,Farkash S,Hecht M,Zimmerman J,Eden E,Yakhini Z,Ben-Shushan E,Reubinoff BE,Bergman Y,Simon I,Cedar H

    更新日期：2007-02-01 00:00:00

  • Next-generation association studies for complex traits.

    abstract：:A new study successfully applies complementary whole-genome sequencing and imputation approaches to establish robust disease associations in an isolated population. This strategy is poised to help elucidate the role of variants at the low end of the allele frequency spectrum in the genetic architecture of complex trai...

    journal_title：Nature genetics

    pub_type： 评论,新闻

    doi：10.1038/ng0411-287

    authors： Zeggini E

    更新日期：2011-03-29 00:00:00

  • Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence.

    abstract：:The homeodomain protein IPF1 (also known as IDX1, STF1 and PDX1; see Methods) is critical for development of the pancreas in mice and is a key factor for the regulation of the insulin gene in the beta-cells of the endocrine pancreas. Targeted disruption of the Ipf1 gene encoding IPF1 in transgenic mice results in a fa...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0197-106

    authors： Stoffers DA,Zinkin NT,Stanojevic V,Clarke WL,Habener JF

    更新日期：1997-01-01 00:00:00

  • Structural forms of the human amylase locus and their relationships to SNPs, haplotypes and obesity.

    abstract：:Hundreds of genes reside in structurally complex, poorly understood regions of the human genome. One such region contains the three amylase genes (AMY2B, AMY2A and AMY1) responsible for digesting starch into sugar. Copy number of AMY1 is reported to be the largest genomic influence on obesity, although genome-wide ass...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3340

    authors： Usher CL,Handsaker RE,Esko T,Tuke MA,Weedon MN,Hastie AR,Cao H,Moon JE,Kashin S,Fuchsberger C,Metspalu A,Pato CN,Pato MT,McCarthy MI,Boehnke M,Altshuler DM,Frayling TM,Hirschhorn JN,McCarroll SA

    更新日期：2015-08-01 00:00:00

  • Mutations in a polycistronic nuclear gene associated with molybdenum cofactor deficiency.

    abstract：:All molybdoenzymes other than nitrogenase require molybdopterin as a metal-binding cofactor. Several genes necessary for the synthesis of the molybdenum cofactor (MoCo) have been characterized in bacteria and plants. The proteins encoded by the Escherichia coli genes moaA and moaC catalyse the first steps in MoCo synt...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/1706

    authors： Reiss J,Cohen N,Dorche C,Mandel H,Mendel RR,Stallmeyer B,Zabot MT,Dierks T

    更新日期：1998-09-01 00:00:00

  • Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets.

    abstract：:Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with human complex traits. However, the genes or functional DNA elements through which these variants exert their effects on the traits are often unknown. We propose a method (called SMR) that integrates summary-level data ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3538

    authors： Zhu Z,Zhang F,Hu H,Bakshi A,Robinson MR,Powell JE,Montgomery GW,Goddard ME,Wray NR,Visscher PM,Yang J

    更新日期：2016-05-01 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

  • Understanding multicellular function and disease with human tissue-specific networks.

    abstract：:Tissue and cell-type identity lie at the core of human physiology and disease. Understanding the genetic underpinnings of complex tissues and individual cell lineages is crucial for developing improved diagnostics and therapeutics. We present genome-wide functional interaction networks for 144 human tissues and cell t...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3259

    authors： Greene CS,Krishnan A,Wong AK,Ricciotti E,Zelaya RA,Himmelstein DS,Zhang R,Hartmann BM,Zaslavsky E,Sealfon SC,Chasman DI,FitzGerald GA,Dolinski K,Grosser T,Troyanskaya OG

    更新日期：2015-06-01 00:00:00

  • Soundbites.

    abstract：:Dentinogenesis imperfecta (DGI) is characterized by discolored teeth with an opalescent sheen and dentin that fails to support enamel, causing it to easily chip. Two new studies show that DGI is associated with mutations in DSPP, a gene encoding dentin sialophosphoprotein that is processed into two proteins: dentin si...

    journal_title：Nature genetics

    pub_type： 评论,杂志文章

    doi：10.1038/84728

    authors： Patel P

    更新日期：2001-02-01 00:00:00

  • Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer.

    abstract：:We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated the top SNP in nine European populations. A missense variant (rs2294008) in the PSCA gene showed consistent association ...

    journal_title：Nature genetics

    pub_type： 信件

    doi：10.1038/ng.421

    authors： Wu X,Ye Y,Kiemeney LA,Sulem P,Rafnar T,Matullo G,Seminara D,Yoshida T,Saeki N,Andrew AS,Dinney CP,Czerniak B,Zhang ZF,Kiltie AE,Bishop DT,Vineis P,Porru S,Buntinx F,Kellen E,Zeegers MP,Kumar R,Rudnai P,Gurzau

    更新日期：2009-09-01 00:00:00

  • Genome-wide association study of PR interval.

    abstract：:The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AG...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.517

    authors： Pfeufer A,van Noord C,Marciante KD,Arking DE,Larson MG,Smith AV,Tarasov KV,Müller M,Sotoodehnia N,Sinner MF,Verwoert GC,Li M,Kao WH,Köttgen A,Coresh J,Bis JC,Psaty BM,Rice K,Rotter JI,Rivadeneira F,Hofman A,Kors

    更新日期：2010-02-01 00:00:00

  • Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing.

    abstract：:We sequenced eight melanoma exomes to identify new somatic mutations in metastatic melanoma. Focusing on the mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) family, we found that 24% of melanoma cell lines have mutations in the protein-coding regions of either MAP3K5 or MAP3K9. Structural modeling predict...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.1041

    authors： Stark MS,Woods SL,Gartside MG,Bonazzi VF,Dutton-Regester K,Aoude LG,Chow D,Sereduk C,Niemi NM,Tang N,Ellis JJ,Reid J,Zismann V,Tyagi S,Muzny D,Newsham I,Wu Y,Palmer JM,Pollak T,Youngkin D,Brooks BR,Lanagan C,S

    更新日期：2011-12-25 00:00:00

  • The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein.

    abstract：:Autosomal recessive polycystic kidney disease (ARPKD) is characterized by dilation of collecting ducts and by biliary dysgenesis and is an important cause of renal- and liver-related morbidity and mortality. Genetic analysis of a rat with recessive polycystic kidney disease revealed an orthologous relationship between...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng833

    authors： Ward CJ,Hogan MC,Rossetti S,Walker D,Sneddon T,Wang X,Kubly V,Cunningham JM,Bacallao R,Ishibashi M,Milliner DS,Torres VE,Harris PC

    更新日期：2002-03-01 00:00:00

  • Ancestry estimation and control of population stratification for sequence-based association studies.

    abstract：:Estimating individual ancestry is important in genetic association studies where population structure leads to false positive signals, although assigning ancestry remains challenging with targeted sequence data. We propose a new method for the accurate estimation of individual genetic ancestry, based on direct analysi...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2924

    authors： Wang C,Zhan X,Bragg-Gresham J,Kang HM,Stambolian D,Chew EY,Branham KE,Heckenlively J,FUSION Study.,Fulton R,Wilson RK,Mardis ER,Lin X,Swaroop A,Zöllner S,Abecasis GR

    更新日期：2014-04-01 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

  • Mutations in SDHC cause autosomal dominant paraganglioma, type 3.

    abstract：:Nonchromaffin paragangliomas (PGLs) are usually benign, neural-crest-derived, slow-growing tumours of parasympathetic ganglia. Between 10% and 50% of cases are familial and are transmitted as autosomal dominant traits with incomplete and age-dependent penetrance. ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/81551

    authors： Niemann S,Müller U

    更新日期：2000-11-01 00:00:00

  • Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types.

    abstract：:We introduce an approach to identify disease-relevant tissues and cell types by analyzing gene expression data together with genome-wide association study (GWAS) summary statistics. Our approach uses stratified linkage disequilibrium (LD) score regression to test whether disease heritability is enriched in regions sur...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-018-0081-4

    authors： Finucane HK,Reshef YA,Anttila V,Slowikowski K,Gusev A,Byrnes A,Gazal S,Loh PR,Lareau C,Shoresh N,Genovese G,Saunders A,Macosko E,Pollack S,Brainstorm Consortium.,Perry JRB,Buenrostro JD,Bernstein BE,Raychaudhuri S,M

    更新日期：2018-04-01 00:00:00

  • Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1).

    abstract：:Hereditary multiple exostoses is an autosomal dominant disorder that is characterized by short stature and multiple, benign bone tumours. In a majority of families, the genetic defect (EXT1) is linked to the Langer-Giedion syndrome chromosomal region in 8q24.1. From this region we have cloned and characterized a cDNA ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1095-137

    authors： Ahn J,Lüdecke HJ,Lindow S,Horton WA,Lee B,Wagner MJ,Horsthemke B,Wells DE

    更新日期：1995-10-01 00:00:00

  • Pancreatic cancer risk variant in LINC00673 creates a miR-1231 binding site and interferes with PTPN11 degradation.

    abstract：:Genome-wide association studies have identified several loci associated with pancreatic cancer risk; however, the mechanisms by which genetic factors influence the development of sporadic pancreatic cancer remain largely unknown. Here, by using genome-wide association analysis and functional characterization, we ident...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3568

    authors： Zheng J,Huang X,Tan W,Yu D,Du Z,Chang J,Wei L,Han Y,Wang C,Che X,Zhou Y,Miao X,Jiang G,Yu X,Yang X,Cao G,Zuo C,Li Z,Wang C,Cheung ST,Jia Y,Zheng X,Shen H,Wu C,Lin D

    更新日期：2016-07-01 00:00:00

  • Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome.

    abstract：:The Polycomb repressive complexes PRC1 and PRC2 maintain embryonic stem cell (ESC) pluripotency by silencing lineage-specifying developmental regulator genes. Emerging evidence suggests that Polycomb complexes act through controlling spatial genome organization. We show that PRC1 functions as a master regulator of mou...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3393

    authors： Schoenfelder S,Sugar R,Dimond A,Javierre BM,Armstrong H,Mifsud B,Dimitrova E,Matheson L,Tavares-Cadete F,Furlan-Magaril M,Segonds-Pichon A,Jurkowski W,Wingett SW,Tabbada K,Andrews S,Herman B,LeProust E,Osborne CS,Kose

    更新日期：2015-10-01 00:00:00

  • Renal disease susceptibility and hypertension are under independent genetic control in the fawn-hooded rat.

    abstract：:Hypertension, diabetes and hyperlipidemia are risk factors for life-threatening complications such as end-stage renal disease, coronary artery disease and stroke. Why some patients develop complications is unclear, but only susceptibility genes may be involved. To test this notion, we studied crosses involving the faw...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0196-44

    authors： Brown DM,Provoost AP,Daly MJ,Lander ES,Jacob HJ

    更新日期：1996-01-01 00:00:00

  • DNA repair mediated by endonuclease-independent LINE-1 retrotransposition.

    abstract：:Long interspersed elements (LINE-1s) are abundant retrotransposons in mammalian genomes that probably retrotranspose by target site-primed reverse transcription (TPRT). During TPRT, the LINE-1 endonuclease cleaves genomic DNA, freeing a 3' hydroxyl that serves as a primer for reverse transcription of LINE-1 RNA by LIN...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng898

    authors： Morrish TA,Gilbert N,Myers JS,Vincent BJ,Stamato TD,Taccioli GE,Batzer MA,Moran JV

    更新日期：2002-06-01 00:00:00

  • An evolutionary framework for measuring epigenomic information and estimating cell-type-specific fitness consequences.

    abstract：:Here we ask the question "How much information do epigenomic datasets provide about human genomic function?" We consider nine epigenomic features across 115 cell types and measure information about function as a reduction in entropy under a probabilistic evolutionary model fitted to human and nonhuman primate genomes....

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-018-0300-z

    authors： Gulko B,Siepel A

    更新日期：2019-02-01 00:00:00

  • Activating ESR1 mutations in hormone-resistant metastatic breast cancer.

    abstract：:Breast cancer is the most prevalent cancer in women, and over two-thirds of cases express estrogen receptor-α (ER-α, encoded by ESR1). Through a prospective clinical sequencing program for advanced cancers, we enrolled 11 patients with ER-positive metastatic breast cancer. Whole-exome and transcriptome analysis showed...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2823

    authors： Robinson DR,Wu YM,Vats P,Su F,Lonigro RJ,Cao X,Kalyana-Sundaram S,Wang R,Ning Y,Hodges L,Gursky A,Siddiqui J,Tomlins SA,Roychowdhury S,Pienta KJ,Kim SY,Roberts JS,Rae JM,Van Poznak CH,Hayes DF,Chugh R,Kunju LP,

    更新日期：2013-12-01 00:00:00

  • A murine model of Menkes disease reveals a physiological function of metallothionein.

    abstract：:Human Menkes disease and the murine Mottled phenotype are X-linked diseases that result from copper deficiency due to mutations in a copper-effluxing ATPase, designated ATP7A. Male mice with the Mottled-Brindled allele (Mo-brJ) accumulate copper in the intestine, fail to export copper to peripheral organs and die a fe...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0696-219

    authors： Kelly EJ,Palmiter RD

    更新日期：1996-06-01 00:00:00

  • Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma.

    abstract：:Pediatric midline high-grade astrocytomas (mHGAs) are incurable with few treatment targets identified. Most tumors harbor mutations encoding p.Lys27Met in histone H3 variants. In 40 treatment-naive mHGAs, 39 analyzed by whole-exome sequencing, we find additional somatic mutations specific to tumor location. Gain-of-fu...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2950

    authors： Fontebasso AM,Papillon-Cavanagh S,Schwartzentruber J,Nikbakht H,Gerges N,Fiset PO,Bechet D,Faury D,De Jay N,Ramkissoon LA,Corcoran A,Jones DT,Sturm D,Johann P,Tomita T,Goldman S,Nagib M,Bendel A,Goumnerova L,Bowers

    更新日期：2014-05-01 00:00:00

  • Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.

    abstract：:Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemo...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.466

    authors： Ganesh SK,Zakai NA,van Rooij FJ,Soranzo N,Smith AV,Nalls MA,Chen MH,Kottgen A,Glazer NL,Dehghan A,Kuhnel B,Aspelund T,Yang Q,Tanaka T,Jaffe A,Bis JC,Verwoert GC,Teumer A,Fox CS,Guralnik JM,Ehret GB,Rice K,Feli

    更新日期：2009-11-01 00:00:00

  • Birc2 (cIap1) regulates endothelial cell integrity and blood vessel homeostasis.

    abstract：:Integrity of the blood vessel wall is essential for vascular homeostasis and organ function. A dynamic balance between endothelial cell survival and apoptosis contributes to this integrity during vascular development and pathological angiogenesis. The genetic and molecular mechanisms regulating these processes in vivo...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2007.8

    authors： Santoro MM,Samuel T,Mitchell T,Reed JC,Stainier DY

    更新日期：2007-11-01 00:00:00