7,846 results match your criteria Nature Genetics [Journal]


Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Authors:
Anne E Justice Tugce Karaderi Heather M Highland Kristin L Young Mariaelisa Graff Yingchang Lu Valérie Turcot Paul L Auer Rebecca S Fine Xiuqing Guo Claudia Schurmann Adelheid Lempradl Eirini Marouli Anubha Mahajan Thomas W Winkler Adam E Locke Carolina Medina-Gomez Tõnu Esko Sailaja Vedantam Ayush Giri Ken Sin Lo Tamuno Alfred Poorva Mudgal Maggie C Y Ng Nancy L Heard-Costa Mary F Feitosa Alisa K Manning Sara M Willems Suthesh Sivapalaratnam Goncalo Abecasis Dewan S Alam Matthew Allison Philippe Amouyel Zorayr Arzumanyan Beverley Balkau Lisa Bastarache Sven Bergmann Lawrence F Bielak Matthias Blüher Michael Boehnke Heiner Boeing Eric Boerwinkle Carsten A Böger Jette Bork-Jensen Erwin P Bottinger Donald W Bowden Ivan Brandslund Linda Broer Amber A Burt Adam S Butterworth Mark J Caulfield Giancarlo Cesana John C Chambers Daniel I Chasman Yii-Der Ida Chen Rajiv Chowdhury Cramer Christensen Audrey Y Chu Francis S Collins James P Cook Amanda J Cox David S Crosslin John Danesh Paul I W de Bakker Simon de Denus Renée de Mutsert George Dedoussis Ellen W Demerath Joe G Dennis Josh C Denny Emanuele Di Angelantonio Marcus Dörr Fotios Drenos Marie-Pierre Dubé Alison M Dunning Douglas F Easton Paul Elliott Evangelos Evangelou Aliki-Eleni Farmaki Shuang Feng Ele Ferrannini Jean Ferrieres Jose C Florez Myriam Fornage Caroline S Fox Paul W Franks Nele Friedrich Wei Gan Ilaria Gandin Paolo Gasparini Vilmantas Giedraitis Giorgia Girotto Mathias Gorski Harald Grallert Niels Grarup Megan L Grove Stefan Gustafsson Jeff Haessler Torben Hansen Andrew T Hattersley Caroline Hayward Iris M Heid Oddgeir L Holmen G Kees Hovingh Joanna M M Howson Yao Hu Yi-Jen Hung Kristian Hveem M Arfan Ikram Erik Ingelsson Anne U Jackson Gail P Jarvik Yucheng Jia Torben Jørgensen Pekka Jousilahti Johanne M Justesen Bratati Kahali Maria Karaleftheri Sharon L R Kardia Fredrik Karpe Frank Kee Hidetoshi Kitajima Pirjo Komulainen Jaspal S Kooner Peter Kovacs Bernhard K Krämer Kari Kuulasmaa Johanna Kuusisto Markku Laakso Timo A Lakka David Lamparter Leslie A Lange Claudia Langenberg Eric B Larson Nanette R Lee Wen-Jane Lee Terho Lehtimäki Cora E Lewis Huaixing Li Jin Li Ruifang Li-Gao Li-An Lin Xu Lin Lars Lind Jaana Lindström Allan Linneberg Ching-Ti Liu Dajiang J Liu Jian'an Luan Leo-Pekka Lyytikäinen Stuart MacGregor Reedik Mägi Satu Männistö Gaëlle Marenne Jonathan Marten Nicholas G D Masca Mark I McCarthy Karina Meidtner Evelin Mihailov Leena Moilanen Marie Moitry Dennis O Mook-Kanamori Anna Morgan Andrew P Morris Martina Müller-Nurasyid Patricia B Munroe Narisu Narisu Christopher P Nelson Matt Neville Ioanna Ntalla Jeffrey R O'Connell Katharine R Owen Oluf Pedersen Gina M Peloso Craig E Pennell Markus Perola James A Perry John R B Perry Tune H Pers Ailith Ewing Ozren Polasek Olli T Raitakari Asif Rasheed Chelsea K Raulerson Rainer Rauramaa Dermot F Reilly Alex P Reiner Paul M Ridker Manuel A Rivas Neil R Robertson Antonietta Robino Igor Rudan Katherine S Ruth Danish Saleheen Veikko Salomaa Nilesh J Samani Pamela J Schreiner Matthias B Schulze Robert A Scott Marcelo Segura-Lepe Xueling Sim Andrew J Slater Kerrin S Small Blair H Smith Jennifer A Smith Lorraine Southam Timothy D Spector Elizabeth K Speliotes Kari Stefansson Valgerdur Steinthorsdottir Kathleen E Stirrups Konstantin Strauch Heather M Stringham Michael Stumvoll Liang Sun Praveen Surendran Karin M A Swart Jean-Claude Tardif Kent D Taylor Alexander Teumer Deborah J Thompson Gudmar Thorleifsson Unnur Thorsteinsdottir Betina H Thuesen Anke Tönjes Mina Torres Emmanouil Tsafantakis Jaakko Tuomilehto André G Uitterlinden Matti Uusitupa Cornelia M van Duijn Mauno Vanhala Rohit Varma Sita H Vermeulen Henrik Vestergaard Veronique Vitart Thomas F Vogt Dragana Vuckovic Lynne E Wagenknecht Mark Walker Lars Wallentin Feijie Wang Carol A Wang Shuai Wang Nicholas J Wareham Helen R Warren Dawn M Waterworth Jennifer Wessel Harvey D White Cristen J Willer James G Wilson Andrew R Wood Ying Wu Hanieh Yaghootkar Jie Yao Laura M Yerges-Armstrong Robin Young Eleftheria Zeggini Xiaowei Zhan Weihua Zhang Jing Hua Zhao Wei Zhao He Zheng Wei Zhou M Carola Zillikens Fernando Rivadeneira Ingrid B Borecki J Andrew Pospisilik Panos Deloukas Timothy M Frayling Guillaume Lettre Karen L Mohlke Jerome I Rotter Zoltán Kutalik Joel N Hirschhorn L Adrienne Cupples Ruth J F Loos Kari E North Cecilia M Lindgren

Nat Genet 2019 Feb 18. Epub 2019 Feb 18.

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Read More

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http://dx.doi.org/10.1038/s41588-018-0334-2DOI Listing
February 2019
29.352 Impact Factor

Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis.

Nat Genet 2019 Feb 18. Epub 2019 Feb 18.

Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, TX, USA.

Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. Although a number of large-scale genomic studies of bacterial pathogens have been published, the relationships among the genome, transcriptome, and virulence in large bacterial populations remain poorly understood. We sequenced the genomes of 2,101 emm28 S. Read More

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http://dx.doi.org/10.1038/s41588-018-0343-1DOI Listing
February 2019

Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases.

Nat Genet 2019 Feb 18. Epub 2019 Feb 18.

Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.

Microbiome-wide association studies on large population cohorts have highlighted associations between the gut microbiome and complex traits, including type 2 diabetes (T2D) and obesity. However, the causal relationships remain largely unresolved. We leveraged information from 952 normoglycemic individuals for whom genome-wide genotyping, gut metagenomic sequence and fecal short-chain fatty acid (SCFA) levels were available, then combined this information with genome-wide-association summary statistics for 17 metabolic and anthropometric traits. Read More

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http://dx.doi.org/10.1038/s41588-019-0350-xDOI Listing
February 2019

Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction.

Nat Genet 2019 Feb 18. Epub 2019 Feb 18.

The State Key Laboratory of Cell Biology, CAS Center for Excellence on Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Characterizing the stem cells responsible for lung repair and regeneration is important for the treatment of pulmonary diseases. Recently, a unique cell population located at the bronchioalveolar-duct junctions has been proposed to comprise endogenous stem cells for lung regeneration. However, the role of bronchioalveolar stem cells (BASCs) in vivo remains debated, and the contribution of such cells to lung regeneration is not known. Read More

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http://www.nature.com/articles/s41588-019-0346-6
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http://dx.doi.org/10.1038/s41588-019-0346-6DOI Listing
February 2019
1 Read

Landscape of B cell immunity and related immune evasion in human cancers.

Nat Genet 2019 Feb 11. Epub 2019 Feb 11.

Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Tumor-infiltrating B cells are an important component in the microenvironment but have unclear anti-tumor effects. We enhanced our previous computational algorithm TRUST to extract the B cell immunoglobulin hypervariable regions from bulk tumor RNA-sequencing data. TRUST assembled more than 30 million complementarity-determining region 3 sequences of the B cell heavy chain (IgH) from The Cancer Genome Atlas. Read More

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http://dx.doi.org/10.1038/s41588-018-0339-xDOI Listing
February 2019
1 Read
29.352 Impact Factor

Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration.

Nat Genet 2019 Feb 11. Epub 2019 Feb 11.

Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Genome-wide association studies (GWAS) have identified genetic variants at 34 loci contributing to age-related macular degeneration (AMD). We generated transcriptional profiles of postmortem retinas from 453 controls and cases at distinct stages of AMD and integrated retinal transcriptomes, covering 13,662 protein-coding and 1,462 noncoding genes, with genotypes at more than 9 million common SNPs for expression quantitative trait loci (eQTL) analysis of a tissue not included in Genotype-Tissue Expression (GTEx) and other large datasets. Cis-eQTL analysis identified 10,474 genes under genetic regulation, including 4,541 eQTLs detected only in the retina. Read More

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http://dx.doi.org/10.1038/s41588-019-0351-9DOI Listing
February 2019
29.352 Impact Factor

The landscape of selection in 551 esophageal adenocarcinomas defines genomic biomarkers for the clinic.

Nat Genet 2019 Feb 4. Epub 2019 Feb 4.

MRC cancer unit, Hutchison/MRC research Centre, University of Cambridge, Cambridge, UK.

Esophageal adenocarcinoma (EAC) is a poor-prognosis cancer type with rapidly rising incidence. Understanding of the genetic events driving EAC development is limited, and there are few molecular biomarkers for prognostication or therapeutics. Using a cohort of 551 genomically characterized EACs with matched RNA sequencing data, we discovered 77 EAC driver genes and 21 noncoding driver elements. Read More

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http://www.nature.com/articles/s41588-018-0331-5
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http://dx.doi.org/10.1038/s41588-018-0331-5DOI Listing
February 2019
1 Read

Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population.

Nat Genet 2019 Feb 4. Epub 2019 Feb 4.

Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

To understand the genetics of type 2 diabetes in people of Japanese ancestry, we conducted A meta-analysis of four genome-wide association studies (GWAS; 36,614 cases and 155,150 controls of Japanese ancestry). We identified 88 type 2 diabetes-associated loci (P < 5.0 × 10) with 115 independent signals (P < 5. Read More

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http://www.nature.com/articles/s41588-018-0332-4
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http://dx.doi.org/10.1038/s41588-018-0332-4DOI Listing
February 2019
2 Reads

Genomics and our future food security.

Authors:

Nat Genet 2019 Feb;51(2):197

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http://dx.doi.org/10.1038/s41588-019-0352-8DOI Listing
February 2019

Author Correction: Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism.

Nat Genet 2019 Jan 29. Epub 2019 Jan 29.

Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, University of Edinburgh, Edinburgh, UK.

In the version of this article initially published, in Table 2, the descriptions of pathways and definitions in the first and last columns did not correctly correspond to the values in the other columns. The error has been corrected in the HTML and PDF versions of the article. Read More

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http://dx.doi.org/10.1038/s41588-019-0357-3DOI Listing
January 2019

Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population.

Nat Genet 2019 Jan 28. Epub 2019 Jan 28.

Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.

To perform detailed fine-mapping of the major-histocompatibility-complex region, we conducted next-generation sequencing (NGS)-based typing of the 33 human leukocyte antigen (HLA) genes in 1,120 individuals of Japanese ancestry, providing a high-resolution allele catalog and linkage-disequilibrium structure of both classical and nonclassical HLA genes. Together with population-specific deep-whole-genome-sequencing data (n = 1,276), we conducted NGS-based HLA, single-nucleotide-variant and indel imputation of large-scale genome-wide-association-study data from 166,190 Japanese individuals. A phenome-wide association study assessing 106 clinical phenotypes identified abundant, significant genotype-phenotype associations across 52 phenotypes. Read More

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http://dx.doi.org/10.1038/s41588-018-0336-0DOI Listing
January 2019
1 Read

EZH2 oncogenic mutations drive epigenetic, transcriptional, and structural changes within chromatin domains.

Nat Genet 2019 Jan 28. Epub 2019 Jan 28.

Swiss Institute for Experimental Cancer Research (ISREC), School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Chromatin is organized into topologically associating domains (TADs) enriched in distinct histone marks. In cancer, gain-of-function mutations in the gene encoding the enhancer of zeste homolog 2 protein (EZH2) lead to a genome-wide increase in histone-3 Lys27 trimethylation (H3K27me3) associated with transcriptional repression. However, the effects of these epigenetic changes on the structure and function of chromatin domains have not been explored. Read More

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http://www.nature.com/articles/s41588-018-0338-y
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http://dx.doi.org/10.1038/s41588-018-0338-yDOI Listing
January 2019
4 Reads

GARFIELD classifies disease-relevant genomic features through integration of functional annotations with association signals.

Nat Genet 2019 Feb 28;51(2):343-353. Epub 2019 Jan 28.

Human Genetics, Wellcome Sanger Institute, Hinxton, UK.

Loci discovered by genome-wide association studies predominantly map outside protein-coding genes. The interpretation of the functional consequences of non-coding variants can be greatly enhanced by catalogs of regulatory genomic regions in cell lines and primary tissues. However, robust and readily applicable methods are still lacking by which to systematically evaluate the contribution of these regions to genetic variation implicated in diseases or quantitative traits. Read More

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http://dx.doi.org/10.1038/s41588-018-0322-6DOI Listing
February 2019

Harnessing the potential of germplasm collections.

Nat Genet 2019 Feb;51(2):200-201

School of Agriculture, Food and Wine, University of Adelaide, Adelaide, South Australia, Australia.

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http://dx.doi.org/10.1038/s41588-018-0340-4DOI Listing
February 2019

Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data.

Nat Genet 2019 Feb 21;51(2):230-236. Epub 2019 Jan 21.

Human Genetics, Wellcome Genome Campus, Wellcome Sanger Institute, Cambridge, UK.

Osteoarthritis is the most common musculoskeletal disease and the leading cause of disability globally. Here, we performed a genome-wide association study for osteoarthritis (77,052 cases and 378,169 controls), analyzing four phenotypes: knee osteoarthritis, hip osteoarthritis, knee and/or hip osteoarthritis, and any osteoarthritis. We discovered 64 signals, 52 of them novel, more than doubling the number of established disease loci. Read More

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http://dx.doi.org/10.1038/s41588-018-0327-1DOI Listing
February 2019
2 Reads

Author Correction: Assembly of a pan-genome from deep sequencing of 910 humans of African descent.

Nat Genet 2019 Feb;51(2):364

Center for Computational Biology, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA.

In the version of this article initially published, the statement "there are no pan-genomes for any other animal or plant species" was incorrect. The statement has been corrected to "there are no reported pan-genomes for any other animal species, to our knowledge." We thank David Edwards for bringing this error to our attention. Read More

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http://www.nature.com/articles/s41588-018-0335-1
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http://dx.doi.org/10.1038/s41588-018-0335-1DOI Listing
February 2019
5 Reads

Publisher Correction: Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments.

Nat Genet 2019 Feb;51(2):364

Gene Expression and Biophysics Group, Division of Chemical, Systems and Synthetic Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

In the version of this article initially published, '+' and '-' labels were missing from the graph keys at the bottom of Fig. 8d. The error has been corrected in the HTML and PDF versions of the article. Read More

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http://dx.doi.org/10.1038/s41588-018-0341-3DOI Listing
February 2019

Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences.

Nat Genet 2019 Feb 14;51(2):245-257. Epub 2019 Jan 14.

Department of Economics, University of Toronto, Toronto, Ontario, Canada.

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. Read More

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http://dx.doi.org/10.1038/s41588-018-0309-3DOI Listing
February 2019
4 Reads
29.352 Impact Factor

Fast and accurate genomic analyses using genome graphs.

Nat Genet 2019 Feb 14;51(2):354-362. Epub 2019 Jan 14.

Seven Bridges Genomics, Inc, Cambridge, MA, USA.

The human reference genome serves as the foundation for genomics by providing a scaffold for alignment of sequencing reads, but currently only reflects a single consensus haplotype, thus impairing analysis accuracy. Here we present a graph reference genome implementation that enables read alignment across 2,800 diploid genomes encompassing 12.6 million SNPs and 4. Read More

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http://dx.doi.org/10.1038/s41588-018-0316-4DOI Listing
February 2019

Multivariate genome-wide analyses of the well-being spectrum.

Nat Genet 2019 Jan 14. Epub 2019 Jan 14.

Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

We introduce two novel methods for multivariate genome-wide-association meta-analysis (GWAMA) of related traits that correct for sample overlap. A broad range of simulation scenarios supports the added value of our multivariate methods relative to univariate GWAMA. We applied the novel methods to life satisfaction, positive affect, neuroticism, and depressive symptoms, collectively referred to as the well-being spectrum (N = 2,370,390), and found 304 significant independent signals. Read More

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http://dx.doi.org/10.1038/s41588-018-0320-8DOI Listing
January 2019
1 Read

Tumor mutational load predicts survival after immunotherapy across multiple cancer types.

Nat Genet 2019 Feb 14;51(2):202-206. Epub 2019 Jan 14.

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in selected cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI. To examine this association more broadly, we analyzed the clinical and genomic data of 1,662 advanced cancer patients treated with ICI, and 5,371 non-ICI-treated patients, whose tumors underwent targeted next-generation sequencing (MSK-IMPACT). Read More

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http://dx.doi.org/10.1038/s41588-018-0312-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365097PMC
February 2019
18 Reads
29.352 Impact Factor

Repurposing large health insurance claims data to estimate genetic and environmental contributions in 560 phenotypes.

Nat Genet 2019 Feb 14;51(2):327-334. Epub 2019 Jan 14.

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.

We analysed a large health insurance dataset to assess the genetic and environmental contributions of 560 disease-related phenotypes in 56,396 twin pairs and 724,513 sibling pairs out of 44,859,462 individuals that live in the United States. We estimated the contribution of environmental risk factors (socioeconomic status (SES), air pollution and climate) in each phenotype. Mean heritability (h = 0. Read More

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http://dx.doi.org/10.1038/s41588-018-0313-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358510PMC
February 2019
1 Read
29.352 Impact Factor

Nuclear positioning and pairing of X-chromosome inactivation centers are not primary determinants during initiation of random X-inactivation.

Nat Genet 2019 Feb 14;51(2):285-295. Epub 2019 Jan 14.

Mammalian Developmental Epigenetics Group, Genetics and Developmental Biology Unit, Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.

During X-chromosome inactivation (XCI), one of the two X-inactivation centers (Xics) upregulates the noncoding RNA Xist to initiate chromosomal silencing in cis. How one Xic is chosen to upregulate Xist remains unclear. Models proposed include localization of one Xic at the nuclear envelope or transient homologous Xic pairing followed by asymmetric transcription factor distribution at Xist's antisense Xite/Tsix locus. Read More

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http://dx.doi.org/10.1038/s41588-018-0305-7DOI Listing
February 2019

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Authors:
Mengzhen Liu Yu Jiang Robbee Wedow Yue Li David M Brazel Fang Chen Gargi Datta Jose Davila-Velderrain Daniel McGuire Chao Tian Xiaowei Zhan Hélène Choquet Anna R Docherty Jessica D Faul Johanna R Foerster Lars G Fritsche Maiken Elvestad Gabrielsen Scott D Gordon Jeffrey Haessler Jouke-Jan Hottenga Hongyan Huang Seon-Kyeong Jang Philip R Jansen Yueh Ling Reedik Mägi Nana Matoba George McMahon Antonella Mulas Valeria Orrù Teemu Palviainen Anita Pandit Gunnar W Reginsson Anne Heidi Skogholt Jennifer A Smith Amy E Taylor Constance Turman Gonneke Willemsen Hannah Young Kendra A Young Gregory J M Zajac Wei Zhao Wei Zhou Gyda Bjornsdottir Jason D Boardman Michael Boehnke Dorret I Boomsma Chu Chen Francesco Cucca Gareth E Davies Charles B Eaton Marissa A Ehringer Tõnu Esko Edoardo Fiorillo Nathan A Gillespie Daniel F Gudbjartsson Toomas Haller Kathleen Mullan Harris Andrew C Heath John K Hewitt Ian B Hickie John E Hokanson Christian J Hopfer David J Hunter William G Iacono Eric O Johnson Yoichiro Kamatani Sharon L R Kardia Matthew C Keller Manolis Kellis Charles Kooperberg Peter Kraft Kenneth S Krauter Markku Laakso Penelope A Lind Anu Loukola Sharon M Lutz Pamela A F Madden Nicholas G Martin Matt McGue Matthew B McQueen Sarah E Medland Andres Metspalu Karen L Mohlke Jonas B Nielsen Yukinori Okada Ulrike Peters Tinca J C Polderman Danielle Posthuma Alexander P Reiner John P Rice Eric Rimm Richard J Rose Valgerdur Runarsdottir Michael C Stallings Alena Stančáková Hreinn Stefansson Khanh K Thai Hilary A Tindle Thorarinn Tyrfingsson Tamara L Wall David R Weir Constance Weisner John B Whitfield Bendik Slagsvold Winsvold Jie Yin Luisa Zuccolo Laura J Bierut Kristian Hveem James J Lee Marcus R Munafò Nancy L Saccone Cristen J Willer Marilyn C Cornelis Sean P David David A Hinds Eric Jorgenson Jaakko Kaprio Jerry A Stitzel Kari Stefansson Thorgeir E Thorgeirsson Gonçalo Abecasis Dajiang J Liu Scott Vrieze

Nat Genet 2019 Feb 14;51(2):237-244. Epub 2019 Jan 14.

Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders. They are heritable and etiologically related behaviors that have been resistant to gene discovery efforts. In sample sizes up to 1. Read More

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http://www.nature.com/articles/s41588-018-0307-5
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http://dx.doi.org/10.1038/s41588-018-0307-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358542PMC
February 2019
7 Reads

Molecular landmarks of tumor hypoxia across cancer types.

Nat Genet 2019 Feb 14;51(2):308-318. Epub 2019 Jan 14.

Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.

Many primary-tumor subregions have low levels of molecular oxygen, termed hypoxia. Hypoxic tumors are at elevated risk for local failure and distant metastasis, but the molecular hallmarks of tumor hypoxia remain poorly defined. To fill this gap, we quantified hypoxia in 8,006 tumors across 19 tumor types. Read More

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http://www.nature.com/articles/s41588-018-0318-2
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http://dx.doi.org/10.1038/s41588-018-0318-2DOI Listing
February 2019
9 Reads

PAX5-driven subtypes of B-progenitor acute lymphoblastic leukemia.

Nat Genet 2019 Feb 14;51(2):296-307. Epub 2019 Jan 14.

Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Recent genomic studies have identified chromosomal rearrangements defining new subtypes of B-progenitor acute lymphoblastic leukemia (B-ALL), however many cases lack a known initiating genetic alteration. Using integrated genomic analysis of 1,988 childhood and adult cases, we describe a revised taxonomy of B-ALL incorporating 23 subtypes defined by chromosomal rearrangements, sequence mutations or heterogeneous genomic alterations, many of which show marked variation in prevalence according to age. Two subtypes have frequent alterations of the B lymphoid transcription-factor gene PAX5. Read More

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http://www.nature.com/articles/s41588-018-0315-5
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http://dx.doi.org/10.1038/s41588-018-0315-5DOI Listing
February 2019
20 Reads

The genetic basis of inbreeding depression in potato.

Nat Genet 2019 Jan 14. Epub 2019 Jan 14.

Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.

Inbreeding depression confers reduced fitness among the offspring of genetic relatives. As a clonally propagated crop, potato (Solanum tuberosum L.) suffers from severe inbreeding depression; however, the genetic basis of inbreeding depression in potato is largely unknown. Read More

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http://www.nature.com/articles/s41588-018-0319-1
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http://dx.doi.org/10.1038/s41588-018-0319-1DOI Listing
January 2019
36 Reads

Author Correction: Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.

Authors:
Fredrick R Schumacher Ali Amin Al Olama Sonja I Berndt Sara Benlloch Mahbubl Ahmed Edward J Saunders Tokhir Dadaev Daniel Leongamornlert Ezequiel Anokian Clara Cieza-Borrella Chee Goh Mark N Brook Xin Sheng Laura Fachal Joe Dennis Jonathan Tyrer Kenneth Muir Artitaya Lophatananon Victoria L Stevens Susan M Gapstur Brian D Carter Catherine M Tangen Phyllis J Goodman Ian M Thompson Jyotsna Batra Suzanne Chambers Leire Moya Judith Clements Lisa Horvath Wayne Tilley Gail P Risbridger Henrik Gronberg Markus Aly Tobias Nordström Paul Pharoah Nora Pashayan Johanna Schleutker Teuvo L J Tammela Csilla Sipeky Anssi Auvinen Demetrius Albanes Stephanie Weinstein Alicja Wolk Niclas Håkansson Catharine M L West Alison M Dunning Neil Burnet Lorelei A Mucci Edward Giovannucci Gerald L Andriole Olivier Cussenot Géraldine Cancel-Tassin Stella Koutros Laura E Beane Freeman Karina Dalsgaard Sorensen Torben Falck Orntoft Michael Borre Lovise Maehle Eli Marie Grindedal David E Neal Jenny L Donovan Freddie C Hamdy Richard M Martin Ruth C Travis Tim J Key Robert J Hamilton Neil E Fleshner Antonio Finelli Sue Ann Ingles Mariana C Stern Barry S Rosenstein Sarah L Kerns Harry Ostrer Yong-Jie Lu Hong-Wei Zhang Ninghan Feng Xueying Mao Xin Guo Guomin Wang Zan Sun Graham G Giles Melissa C Southey Robert J MacInnis Liesel M FitzGerald Adam S Kibel Bettina F Drake Ana Vega Antonio Gómez-Caamaño Robert Szulkin Martin Eklund Manolis Kogevinas Javier Llorca Gemma Castaño-Vinyals Kathryn L Penney Meir Stampfer Jong Y Park Thomas A Sellers Hui-Yi Lin Janet L Stanford Cezary Cybulski Dominika Wokolorczyk Jan Lubinski Elaine A Ostrander Milan S Geybels Børge G Nordestgaard Sune F Nielsen Maren Weischer Rasmus Bisbjerg Martin Andreas Røder Peter Iversen Hermann Brenner Katarina Cuk Bernd Holleczek Christiane Maier Manuel Luedeke Thomas Schnoeller Jeri Kim Christopher J Logothetis Esther M John Manuel R Teixeira Paula Paulo Marta Cardoso Susan L Neuhausen Linda Steele Yuan Chun Ding Kim De Ruyck Gert De Meerleer Piet Ost Azad Razack Jasmine Lim Soo-Hwang Teo Daniel W Lin Lisa F Newcomb Davor Lessel Marija Gamulin Tomislav Kulis Radka Kaneva Nawaid Usmani Sandeep Singhal Chavdar Slavov Vanio Mitev Matthew Parliament Frank Claessens Steven Joniau Thomas Van den Broeck Samantha Larkin Paul A Townsend Claire Aukim-Hastie Manuela Gago-Dominguez Jose Esteban Castelao Maria Elena Martinez Monique J Roobol Guido Jenster Ron H N van Schaik Florence Menegaux Thérèse Truong Yves Akoli Koudou Jianfeng Xu Kay-Tee Khaw Lisa Cannon-Albright Hardev Pandha Agnieszka Michael Stephen N Thibodeau Shannon K McDonnell Daniel J Schaid Sara Lindstrom Constance Turman Jing Ma David J Hunter Elio Riboli Afshan Siddiq Federico Canzian Laurence N Kolonel Loic Le Marchand Robert N Hoover Mitchell J Machiela Zuxi Cui Peter Kraft Christopher I Amos David V Conti Douglas F Easton Fredrik Wiklund Stephen J Chanock Brian E Henderson Zsofia Kote-Jarai Christopher A Haiman Rosalind A Eeles

Nat Genet 2019 Feb;51(2):363

Institute of Cancer Research, London, UK.

In the version of this article initially published, the name of author Manuela Gago-Dominguez was misspelled as Manuela Gago Dominguez. The error has been corrected in the HTML and PDF version of the article. Read More

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http://www.nature.com/articles/s41588-018-0330-6
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http://dx.doi.org/10.1038/s41588-018-0330-6DOI Listing
February 2019
13 Reads
29.352 Impact Factor

Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.

Nat Genet 2019 Jan 7. Epub 2019 Jan 7.

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam, the Netherlands.

Alzheimer's disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). Read More

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http://dx.doi.org/10.1038/s41588-018-0311-9DOI Listing
January 2019
12 Reads
29.352 Impact Factor

GADD45A binds R-loops and recruits TET1 to CpG island promoters.

Nat Genet 2019 Feb 7;51(2):217-223. Epub 2019 Jan 7.

Institute of Molecular Biology (IMB), Mainz, Germany.

R-loops are DNA-RNA hybrids enriched at CpG islands (CGIs) that can regulate chromatin states. How R-loops are recognized and interpreted by specific epigenetic readers is unknown. Here we show that GADD45A (growth arrest and DNA damage protein 45A) binds directly to R-loops and mediates local DNA demethylation by recruiting TET1 (ten-eleven translocation 1). Read More

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http://www.nature.com/articles/s41588-018-0306-6
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http://dx.doi.org/10.1038/s41588-018-0306-6DOI Listing
February 2019
13 Reads

Double-outlet right ventricle is not hypoplastic left heart syndrome.

Nat Genet 2019 Feb;51(2):198

Cardiovascular Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.

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http://dx.doi.org/10.1038/s41588-018-0324-4DOI Listing
February 2019

Reply to 'Double-outlet right ventricle is not hypoplastic left heart syndrome'.

Nat Genet 2019 Feb;51(2):198-199

Pediatric Cardiology, Medical College of Wisconsin, Milwaukee, WI, USA.

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http://dx.doi.org/10.1038/s41588-018-0323-5DOI Listing
February 2019

An atlas of genetic influences on osteoporosis in humans and mice.

Nat Genet 2019 Feb 31;51(2):258-266. Epub 2018 Dec 31.

Department of Human Genetics, McGill University, Montréal, Québec, Canada.

Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1. Read More

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http://dx.doi.org/10.1038/s41588-018-0302-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358485PMC
February 2019
3 Reads
29.352 Impact Factor

Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.

Authors:
Ayush Giri Jacklyn N Hellwege Jacob M Keaton Jihwan Park Chengxiang Qiu Helen R Warren Eric S Torstenson Csaba P Kovesdy Yan V Sun Otis D Wilson Cassianne Robinson-Cohen Christianne L Roumie Cecilia P Chung Kelly A Birdwell Scott M Damrauer Scott L DuVall Derek Klarin Kelly Cho Yu Wang Evangelos Evangelou Claudia P Cabrera Louise V Wain Rojesh Shrestha Brian S Mautz Elvis A Akwo Muralidharan Sargurupremraj Stéphanie Debette Michael Boehnke Laura J Scott Jian'an Luan Jing-Hua Zhao Sara M Willems Sébastien Thériault Nabi Shah Christopher Oldmeadow Peter Almgren Ruifang Li-Gao Niek Verweij Thibaud S Boutin Massimo Mangino Ioanna Ntalla Elena Feofanova Praveen Surendran James P Cook Savita Karthikeyan Najim Lahrouchi Chunyu Liu Nuno Sepúlveda Tom G Richardson Aldi Kraja Philippe Amouyel Martin Farrall Neil R Poulter Markku Laakso Eleftheria Zeggini Peter Sever Robert A Scott Claudia Langenberg Nicholas J Wareham David Conen Colin Neil Alexander Palmer John Attia Daniel I Chasman Paul M Ridker Olle Melander Dennis Owen Mook-Kanamori Pim van der Harst Francesco Cucca David Schlessinger Caroline Hayward Tim D Spector Marjo-Riitta Jarvelin Branwen J Hennig Nicholas J Timpson Wei-Qi Wei Joshua C Smith Yaomin Xu Michael E Matheny Edward E Siew Cecilia Lindgren Karl-Heinz Herzig George Dedoussis Joshua C Denny Bruce M Psaty Joanna M M Howson Patricia B Munroe Christopher Newton-Cheh Mark J Caulfield Paul Elliott J Michael Gaziano John Concato Peter W F Wilson Philip S Tsao Digna R Velez Edwards Katalin Susztak Christopher J O'Donnell Adriana M Hung Todd L Edwards

Nat Genet 2019 Jan 21;51(1):51-62. Epub 2018 Dec 21.

Biomedical Laboratory Research and Development, Tennessee Valley Healthcare System (626)/Vanderbilt University, Nashville, TN, USA.

In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically predicted gene expression of 840 genes in 45 tissues, and mouse renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells. Read More

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http://www.nature.com/articles/s41588-018-0303-9
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http://dx.doi.org/10.1038/s41588-018-0303-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365102PMC
January 2019
11 Reads

The copy number variation landscape of congenital anomalies of the kidney and urinary tract.

Nat Genet 2019 Jan 21;51(1):117-127. Epub 2018 Dec 21.

Division of Nephrology, Department of Medicine, Columbia University, New York, NY, USA.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Read More

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http://www.nature.com/articles/s41588-018-0281-y
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http://dx.doi.org/10.1038/s41588-018-0281-yDOI Listing
January 2019
13 Reads

Deep learning for genomics.

Authors:

Nat Genet 2019 Jan;51(1)

Application of deep learning to genomic datasets is an exciting area that is rapidly developing and is primed to revolutionize genome analysis. We embrace the potential that deep learning holds for understanding genome biology, and we encourage further advances in this area, extending to all aspects of genomics research. Read More

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http://dx.doi.org/10.1038/s41588-018-0328-0DOI Listing
January 2019

Author Correction: Predicting the clinical impact of human mutation with deep neural networks.

Nat Genet 2019 Feb;51(2):364

Illumina Artificial Intelligence Laboratory, Illumina Inc, San Diego, CA, USA.

In the version of this article originally published, the name of author Serafim Batzoglou was misspelled. The error has been corrected in the HTML and PDF versions of the article. Read More

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http://dx.doi.org/10.1038/s41588-018-0329-zDOI Listing
February 2019

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

Nat Genet 2019 Feb 17;51(2):335-342. Epub 2018 Dec 17.

Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.

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. Several epigenomic features yield more information in combination than they do individually. We find that the entropy in human genetic variation predominantly reflects a balance between mutation and neutral drift. Read More

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http://dx.doi.org/10.1038/s41588-018-0300-zDOI Listing
February 2019

Single-cell and single-molecule epigenomics to uncover genome regulation at unprecedented resolution.

Nat Genet 2019 Jan 17;51(1):19-25. Epub 2018 Dec 17.

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Recent advances in single-cell and single-molecule epigenomic technologies now enable the study of genome regulation and dynamics at unprecedented resolution. In this Perspective, we highlight some of these transformative technologies and discuss how they have been used to identify new modes of gene regulation. We also contrast these assays with recent advances in single-cell transcriptomics and argue for the essential role of epigenomic technologies in both understanding cellular diversity and discovering gene regulatory mechanisms. Read More

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http://dx.doi.org/10.1038/s41588-018-0290-xDOI Listing
January 2019

Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity.

Nat Genet 2019 Jan 17;51(1):106-116. Epub 2018 Dec 17.

Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.

We combined de novo mutation (DNM) data from 10,927 individuals with developmental delay and autism to identify 253 candidate neurodevelopmental disease genes with an excess of missense and/or likely gene-disruptive (LGD) mutations. Of these genes, 124 reach exome-wide significance (P < 5 × 10) for DNM. Intersecting these results with copy number variation (CNV) morbidity data shows an enrichment for genomic disorder regions (30/253, likelihood ratio (LR) +1. Read More

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http://dx.doi.org/10.1038/s41588-018-0288-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309590PMC
January 2019
1 Read

Publisher Correction: Cancer genetics, precision prevention and a call to action.

Nat Genet 2019 Jan;51(1):196

Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.

In the version of this article originally published, there was an error in the second-to-last sentence of the abstract. In this sentence, the final phrase "to identify carriers of first-wave gene mutation carriers" should have instead read "to identify carriers of first-wave gene mutation." The error has been corrected in the HTML and PDF versions of the paper. Read More

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http://www.nature.com/articles/s41588-018-0326-2
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http://dx.doi.org/10.1038/s41588-018-0326-2DOI Listing
January 2019
1 Read

Publisher Correction: Selective effects of heterozygous protein-truncating variants.

Nat Genet 2019 Jan;51(1):196

Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.

In the version of this article initially published, reference 10 incorrectly cited Seplyarskiy, V. B. et al. Read More

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http://dx.doi.org/10.1038/s41588-018-0325-3DOI Listing
January 2019

Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments.

Nat Genet 2019 Jan 10;51(1):138-150. Epub 2018 Dec 10.

Gene Expression and Biophysics Group, Division of Chemical, Systems and Synthetic Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

Accumulation of trimethylation of histone H3 at lysine 4 (H3K4me3) on immune-related gene promoters underlies robust transcription during trained immunity. However, the molecular basis for this remains unknown. Here we show three-dimensional chromatin topology enables immune genes to engage in chromosomal contacts with a subset of long noncoding RNAs (lncRNAs) we have defined as immune gene-priming lncRNAs (IPLs). Read More

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http://dx.doi.org/10.1038/s41588-018-0298-2DOI Listing
January 2019

Acquired HER2 mutations in ER metastatic breast cancer confer resistance to estrogen receptor-directed therapies.

Nat Genet 2019 Feb 10;51(2):207-216. Epub 2018 Dec 10.

Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA, USA.

Seventy percent of breast cancers express the estrogen receptor (ER), and agents that target the ER are the mainstay of treatment. However, virtually all people with ER breast cancer develop resistance to ER-directed agents in the metastatic setting. Beyond mutations in the ER itself, which occur in 25-30% of people treated with aromatase inhibitors, knowledge about clinical resistance mechanisms remains incomplete. Read More

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http://dx.doi.org/10.1038/s41588-018-0287-5DOI Listing
February 2019
3 Reads

A map of constrained coding regions in the human genome.

Nat Genet 2019 Jan 10;51(1):88-95. Epub 2018 Dec 10.

Department of Human Genetics, University of Utah, Salt Lake City, UT, USA.

Deep catalogs of genetic variation from thousands of humans enable the detection of intraspecies constraint by identifying coding regions with a scarcity of variation. While existing techniques summarize constraint for entire genes, single gene-wide metrics conceal regional constraint variability within each gene. Therefore, we have created a detailed map of constrained coding regions (CCRs) by leveraging variation observed among 123,136 humans from the Genome Aggregation Database. Read More

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http://dx.doi.org/10.1038/s41588-018-0294-6DOI Listing
January 2019

Opening up a large can of worms.

Authors:
Paul W Sternberg

Nat Genet 2019 Jan;51(1):10-11

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.

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http://dx.doi.org/10.1038/s41588-018-0317-3DOI Listing
January 2019

Discovery of common and rare genetic risk variants for colorectal cancer.

Authors:
Jeroen R Huyghe Stephanie A Bien Tabitha A Harrison Hyun Min Kang Sai Chen Stephanie L Schmit David V Conti Conghui Qu Jihyoun Jeon Christopher K Edlund Peyton Greenside Michael Wainberg Fredrick R Schumacher Joshua D Smith David M Levine Sarah C Nelson Nasa A Sinnott-Armstrong Demetrius Albanes M Henar Alonso Kristin Anderson Coral Arnau-Collell Volker Arndt Christina Bamia Barbara L Banbury John A Baron Sonja I Berndt Stéphane Bézieau D Timothy Bishop Juergen Boehm Heiner Boeing Hermann Brenner Stefanie Brezina Stephan Buch Daniel D Buchanan Andrea Burnett-Hartman Katja Butterbach Bette J Caan Peter T Campbell Christopher S Carlson Sergi Castellví-Bel Andrew T Chan Jenny Chang-Claude Stephen J Chanock Maria-Dolores Chirlaque Sang Hee Cho Charles M Connolly Amanda J Cross Katarina Cuk Keith R Curtis Albert de la Chapelle Kimberly F Doheny David Duggan Douglas F Easton Sjoerd G Elias Faye Elliott Dallas R English Edith J M Feskens Jane C Figueiredo Rocky Fischer Liesel M FitzGerald David Forman Manish Gala Steven Gallinger W James Gauderman Graham G Giles Elizabeth Gillanders Jian Gong Phyllis J Goodman William M Grady John S Grove Andrea Gsur Marc J Gunter Robert W Haile Jochen Hampe Heather Hampel Sophia Harlid Richard B Hayes Philipp Hofer Michael Hoffmeister John L Hopper Wan-Ling Hsu Wen-Yi Huang Thomas J Hudson David J Hunter Gemma Ibañez-Sanz Gregory E Idos Roxann Ingersoll Rebecca D Jackson Eric J Jacobs Mark A Jenkins Amit D Joshi Corinne E Joshu Temitope O Keku Timothy J Key Hyeong Rok Kim Emiko Kobayashi Laurence N Kolonel Charles Kooperberg Tilman Kühn Sébastien Küry Sun-Seog Kweon Susanna C Larsson Cecelia A Laurie Loic Le Marchand Suzanne M Leal Soo Chin Lee Flavio Lejbkowicz Mathieu Lemire Christopher I Li Li Li Wolfgang Lieb Yi Lin Annika Lindblom Noralane M Lindor Hua Ling Tin L Louie Satu Männistö Sanford D Markowitz Vicente Martín Giovanna Masala Caroline E McNeil Marilena Melas Roger L Milne Lorena Moreno Neil Murphy Robin Myte Alessio Naccarati Polly A Newcomb Kenneth Offit Shuji Ogino N Charlotte Onland-Moret Barbara Pardini Patrick S Parfrey Rachel Pearlman Vittorio Perduca Paul D P Pharoah Mila Pinchev Elizabeth A Platz Ross L Prentice Elizabeth Pugh Leon Raskin Gad Rennert Hedy S Rennert Elio Riboli Miguel Rodríguez-Barranco Jane Romm Lori C Sakoda Clemens Schafmayer Robert E Schoen Daniela Seminara Mitul Shah Tameka Shelford Min-Ho Shin Katerina Shulman Sabina Sieri Martha L Slattery Melissa C Southey Zsofia K Stadler Christa Stegmaier Yu-Ru Su Catherine M Tangen Stephen N Thibodeau Duncan C Thomas Sushma S Thomas Amanda E Toland Antonia Trichopoulou Cornelia M Ulrich David J Van Den Berg Franzel J B van Duijnhoven Bethany Van Guelpen Henk van Kranen Joseph Vijai Kala Visvanathan Pavel Vodicka Ludmila Vodickova Veronika Vymetalkova Korbinian Weigl Stephanie J Weinstein Emily White Aung Ko Win C Roland Wolf Alicja Wolk Michael O Woods Anna H Wu Syed H Zaidi Brent W Zanke Qing Zhang Wei Zheng Peter C Scacheri John D Potter Michael C Bassik Anshul Kundaje Graham Casey Victor Moreno Goncalo R Abecasis Deborah A Nickerson Stephen B Gruber Li Hsu Ulrike Peters

Nat Genet 2019 Jan 3;51(1):76-87. Epub 2018 Dec 3.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0. Read More

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http://www.nature.com/articles/s41588-018-0286-6
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http://dx.doi.org/10.1038/s41588-018-0286-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358437PMC
January 2019
27 Reads
29.352 Impact Factor

Error-prone bypass of DNA lesions during lagging-strand replication is a common source of germline and cancer mutations.

Nat Genet 2019 Jan 3;51(1):36-41. Epub 2018 Dec 3.

Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Studies in experimental systems have identified a multitude of mutational mechanisms including DNA replication infidelity and DNA damage followed by inefficient repair or replicative bypass. However, the relative contributions of these mechanisms to human germline mutation remain unknown. Here, we show that error-prone damage bypass on the lagging strand plays a major role in human mutagenesis. Read More

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http://dx.doi.org/10.1038/s41588-018-0285-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317876PMC
January 2019
2 Reads