Nature Genetics Contents: July 2018 Volume 50 Number 7

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Advertisement Adolescence Collection Exploring the science of adolescence and its far-reaching implications for societal challenges  Access the Collection online TABLE OF CONTENTS July 2018 Volume 50, Issue 7 Editorial Correspondence Letters Articles Analysis Technical Reports   Advertisement   Rapidly extract high-quality chromatin from FFPE tissues for ChIP-Seq Formalin-fixed, paraffin-embedded (FFPE) tissues represent a valuable resource for clinical research applications. Samples are routinely fixed in formalin and embedded in paraffin blocks, however, the preservation process makes it difficult to isolate intact biomolecules. The Covaris chromatin extraction workflow is fast, scalable, and reproducible enabling you to accurately profile histone modification and transcription factor binding events. Learn more about how the workflow can make a difference in your lab.    Advertisement Genome Informatics (17-20 September 2018)  This conference will focus on large-scale approaches to understanding the structure and biology of genomes. It will once again bring together computational biologists, human geneticists and others working on comparative and evolutionary genomics. Deadlines: Bursaries: 10 July | Abstracts: 17 July | Registration: 21 August   Advertisement Nature Spotlight on Hong Kong: Building science innovation  Hong Kong is maximising major scientific innovation and commercial benefits through its proximity to the research and development hubs in mainland China. Yet barriers to collaboration remain.  Access the full supplement for more >>    Advertisement nature.com webcasts Nature Research Custom Media presents a webcast on: Practical Considerations for T Cell Receptor (TCR) Therapies Targeting Solid Tumors Date: Tuesday, July 17, 2018 Join the webcast to learn about the advantages of automated cell cloning and methods for rapid cloning and validation of functional TCRs. This webcast has been produced on behalf of the sponsor who retains sole responsibility for content  Register for FREE  Sponsored by: Berkeley Lights Inc    Editorial   Heritable influences on the mind and brain    p905 doi:10.1038/s41588-018-0172-2 Correspondence   Mixed-model association for biobank-scale datasets    pp906 - 908 Po-Ru Loh, Gleb Kichaev, Steven Gazal, Armin P. Schoech & Alkes L. Price doi:10.1038/s41588-018-0144-6 Subfunctionalization versus neofunctionalization after whole-genome duplication    pp908 - 909 Simen R. Sandve, Rori V. Rohlfs & Torgeir R. Hvidsten doi:10.1038/s41588-018-0162-4 Reply to: ‘Subfunctionalization versus neofunctionalization after whole-genome duplication’     pp910 - 911 Ingo Braasch, Julien Bobe, Yann Guiguen & John H. Postlethwait doi:10.1038/s41588-018-0163-3 Nature Genetics JOBS of the week Postdoctoral Fellow - Cancer Research Center Fox Chase Cancer Center (FCCC) Faculty position Sabanci University Post-Doctoral Fellow University of Maryland School of Medicine Postdoctoral Fellow Position Vanderbilt University Medical Center Tenure-Track Faculty Positions Ohio State University More Science jobs from Nature Genetics EVENT The Genetics of Heart and Vascular Disease 12.10.18 Hilton Head Island, USA More science events from Advertisement Do you have a career question?  The Naturejobs podcast features one-on-one Q&As, panel discussions and other exclusive content to help scientists with their careers. Hosted on the Naturejobs blog, the podcast is also available on iTunes and Soundcloud.  Listen today!   Letters   Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence    pp912 - 919 Jeanne E. Savage, Philip R. Jansen, Sven Stringer, Kyoko Watanabe, Julien Bryois et al. doi:10.1038/s41588-018-0152-6 Meta-analysis of genome-wide association studies for cognitive ability identifies 190 new loci and implicates 939 new genes related to neurogenesis, neuron differentiation and synaptic structure.   Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways    pp920 - 927 Mats Nagel, Philip R. Jansen, Sven Stringer, Kyoko Watanabe, Christiaan A. de Leeuw et al. doi:10.1038/s41588-018-0151-7 A meta-analysis of genome-wide association studies for neuroticism identifies novel loci, pathways and potential drug targets. Further analysis implicates specific brain regions and evaluates genetic overlap with other neuropsychiatric traits.   Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci    pp928 - 936 Fredrick R. Schumacher, Ali Amin Al Olama, Sonja I. Berndt, Sara Benlloch, Mahbubl Ahmed et al. doi:10.1038/s41588-018-0142-8 A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.   Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer    pp937 - 943 Srinivas R. Viswanathan, Marina F. Nogueira, Colin G. Buss, John M. Krill-Burger, Mathias J. Wawer et al. doi:10.1038/s41588-018-0155-3 Analysis of paralog gene pairs using data from loss-of-function genetic screens in cancer cells identifies MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types.   Four evolutionary trajectories underlie genetic intratumoral variation in childhood cancer    pp944 - 950 Jenny Karlsson, Anders Valind, Linda Holmquist Mengelbier, Sofia Bredin, Louise Cornmark et al. doi:10.1038/s41588-018-0131-y Multiregional analysis in 54 childhood cancers highlights four evolutionary patterns of intratumoral variation. Multiple patterns are often found in the same tumor, suggesting that tumors follow different evolutionary strategies concurrently.   Defining endemic cholera at three levels of spatiotemporal resolution within Bangladesh    pp951 - 955 Daryl Domman, Fahima Chowdhury, Ashraful I. Khan, Matthew J. Dorman, Ankur Mutreja et al. doi:10.1038/s41588-018-0150-8 Whole-genome sequencing of 303 Vibrio cholerae isolates taken from individuals and households over time in Bangladesh provides insight into the dynamics of cholera diversity and transmission in an endemic setting.   Advertisement Calls for nominations:  2018 John Maddox Prize for Standing up for Science Recognising the work of individuals who promote science in the face of hostility.   Articles   Using an atlas of gene regulation across 44 human tissues to inform complex disease- and trait-associated variation    pp956 - 967 Eric R. Gamazon, Ayellet V. Segrè, Martijn van de Bunt, Xiaoquan Wen, Hualin S. Xi et al. doi:10.1038/s41588-018-0154-4 Integration of expression quantitative trait locus (eQTL) data from the Genotype-Tissue Expression project with genome-wide association study data shows that eQTLs are enriched for trait associations in disease-relevant tissues.   A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer    pp968 - 978 Lang Wu, Wei Shi, Jirong Long, Xingyi Guo, Kyriaki Michailidou et al. doi:10.1038/s41588-018-0132-x A transcriptome-wide association study identifies associations of genetically predicted gene expression with breast cancer risk. This analysis finds 48 candidate genes implicated in breast cancer susceptibility, including 14 at novel loci.   A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors    pp979 - 989 Mariano J. Alvarez, Prem S. Subramaniam, Laura H. Tang, Adina Grunn, Mahalaxmi Aburi et al. doi:10.1038/s41588-018-0138-4 This study presents OncoTreat, a framework for the prioritization of compounds targeting mechanistic tumor dependencies in individual patients.   MiCEE is a ncRNA-protein complex that mediates epigenetic silencing and nucleolar organization    pp990 - 1001 Indrabahadur Singh, Adriana Contreras, Julio Cordero, Karla Rubio, Stephanie Dobersch et al. doi:10.1038/s41588-018-0139-3 The authors describe the MiCEE complex, which comprises Mirlet7d ncRNA duplexes bound by C1D, the RNA exosome complex, and PRC2. MiCEE regulates bidirectionally transcribed loci and nucleolar organization.   MTF2 recruits Polycomb Repressive Complex 2 by helical-shape-selective DNA binding    pp1002 - 1010 Matteo Perino, Guido van Mierlo, Ino D. Karemaker, Siebe van Genesen, Michiel Vermeulen et al. doi:10.1038/s41588-018-0134-8 MTF2 is shown to directly bind DNA and recruit PRC2 in mouse embryonic stem cells. MTF2 selectively binds regions with a high density of unmethylated CpGs in a context of reduced helix twist.   The transcription factor Grainy head primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes    pp1011 - 1020 Jelle Jacobs, Mardelle Atkins, Kristofer Davie, Hana Imrichova, Lucia Romanelli et al. doi:10.1038/s41588-018-0140-x The authors show that the transcription factor Grainy head (Grh) is necessary and sufficient for opening of epithelial enhancers, but not for their activation. Grh is shown to function as a pioneer factor, displacing nucleosomes and paving the way for other transcription factors to activate enhancers.   Gorab is a Golgi protein required for structure and duplication of Drosophila centrioles    pp1021 - 1031 Levente Kovacs, Jennifer Chao-Chu, Sandra Schneider, Marco Gottardo, George Tzolovsky et al. doi:10.1038/s41588-018-0149-1 The roles of of Gorab in the Golgi and in centriole structure and function can be separated mutationally in Drosophila. Complexed to Sas6 in the centriolar cartwheel, Gorab is essential for mitotic centriole duplication in the fly.   An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders    pp1032 - 1040 Siwei Chen, Robert Fragoza, Lambertus Klei, Yuan Liu, Jiebiao Wang et al. doi:10.1038/s41588-018-0130-z An integrated experimental-computational approach evaluates the impact of de novo missense mutations on protein–protein interactions. This interactome-based framework can be used to identify and prioritize disease-associated missense mutations.   Analysis   Leveraging molecular quantitative trait loci to understand the genetic architecture of diseases and complex traits    pp1041 - 1047 Farhad Hormozdiari, Steven Gazal, Bryce van de Geijn, Hilary K. Finucane, Chelsea J.-T. Ju et al. doi:10.1038/s41588-018-0148-2 A new set of functional annotations based on fine-mapped molecular quantitative trait loci from GTEx and BLUEPRINT consortium data are enriched for disease heritability across 41 diseases and complex traits.   De novo variants in neurodevelopmental disorders with epilepsy    pp1048 - 1053 Henrike O. Heyne, Tarjinder Singh, Hannah Stamberger, Rami Abou Jamra, Hande Caglayan et al. doi:10.1038/s41588-018-0143-7 Analysis of individuals with neurodevelopmental disorders (NDDs) with epilepsy identifies 33 genes with a significant excess of de novo variants. Comparison of rates of de novo variants between NDDs with or without epilepsy highlights differences between these phenotypic groups.   Technical Reports   Accurate genotyping across variant classes and lengths using variant graphs    pp1054 - 1059 Jonas Andreas Sibbesen, Lasse Maretty & Anders Krogh doi:10.1038/s41588-018-0145-5 BayesTyper is a new probabilistic genotyping algorithm that offers superior sensitivity and accuracy relative to existing methods by using exact alignment of read k-mers to a graph representation of the reference and candidate variants.   Advertisement Nature Briefing is an essential round-up of science news, opinion and analysis, free in your inbox every weekday. With Nature Briefing, we'll keep you updated on the latest research, so you can focus on yours. Click here to sign up.   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. 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