Large-scale association analyses identify host factors influencing human gut microbiome composition
Alexander Kurilshikov,Carolina Medina-Gomez,Rodrigo Bacigalupe,Djawad Radjabzadeh,Jun Wang,Jun Wang,Ayse Demirkan,Ayse Demirkan,Caroline I. Le Roy,Juan Antonio Raygoza Garay,Casey T. Finnicum,Xingrong Liu,Daria V. Zhernakova,Marc Jan Bonder,Tue H. Hansen,Fabian Frost,Malte C. Rühlemann,Williams Turpin,Jee-Young Moon,Han-Na Kim,Kreete Lüll,Elad Barkan,Shiraz A. Shah,Myriam Fornage,Joanna Szopinska-Tokov,Zachary D. Wallen,Dmitrii Borisevich,Lars Agréus,Anna Andreasson,Corinna Bang,Larbi Bedrani,Jordana T. Bell,Hans Bisgaard,Michael Boehnke,Dorret I. Boomsma,Robert D. Burk,Annique Claringbould,Kenneth Croitoru,Gareth E. Davies,Gareth E. Davies,Cornelia M. van Duijn,Cornelia M. van Duijn,Liesbeth Duijts,Gwen Falony,Jingyuan Fu,Adriaan van der Graaf,Torben Hansen,Georg Homuth,David A. Hughes,Richard G. IJzerman,Matthew A. Jackson,Matthew A. Jackson,Vincent W. V. Jaddoe,Marie Joossens,Torben Jørgensen,Daniel Keszthelyi,Rob Knight,Markku Laakso,Matthias Laudes,Lenore J. Launer,Wolfgang Lieb,Aldons J. Lusis,Ad A.M. Masclee,Henriette A. Moll,Zlatan Mujagic,Qi Qibin,Daphna Rothschild,Hocheol Shin,Søren J. Sørensen,Claire J. Steves,Jonathan Thorsen,Nicholas J. Timpson,Raul Y. Tito,Sara Vieira-Silva,Uwe Völker,Henry Völzke,Urmo Võsa,Kaitlin H Wade,Susanna Walter,Kyoko Watanabe,Stefan Weiss,Frank Ulrich Weiss,Omer Weissbrod,Harm-Jan Westra,Gonneke Willemsen,Haydeh Payami,Daisy Jonkers,Alejandro Arias Vasquez,Eco J. C. de Geus,Katie A. Meyer,Jakob Stokholm,Eran Segal,Elin Org,Cisca Wijmenga,Hyung Lae Kim,Robert C. Kaplan,Tim D. Spector,André G. Uitterlinden,Fernando Rivadeneira,Andre Franke,Markus M. Lerch,Lude Franke,Serena Sanna,Serena Sanna,Mauro D'Amato,Oluf Pedersen,Andrew D. Paterson,Robert Kraaij,Jeroen Raes,Alexandra Zhernakova +109 more
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In this article, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts) and found high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples.Abstract:
To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10−8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10−20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10−10 < P < 5 × 10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.read more
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Microbiome and cancer
Nyssa Cullin,Camila Azevedo Antunes,Ravid Straussman,Christoph K. Stein-Thoeringer,Eran Elinav,Eran Elinav +5 more
TL;DR: The human microbiome constitutes a complex multikingdom community that symbiotically interacts with the host across multiple body sites and has been suggested to influence the development, progression, metastasis formation, and treatment response of multiple cancer types as mentioned in this paper.
Journal ArticleDOI
Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort
Guillaume Méric,Michael Inouye +1 more
TL;DR: In this paper , the authors characterize genetic variations associated with microbial abundances in a single large-scale population-based cohort of 5,959 genotyped individuals with matched gut microbial metagenomes and dietary and health records (prevalent and follow-up).
Journal ArticleDOI
Gut microbiome heritability is nearly universal but environmentally contingent
Laura E. Grieneisen,Mauna Dasari,Trevor J. Gould,Johannes R. Björk,Jean-Christophe Grenier,Vania Yotova,David A. W. A. M. Jansen,Neil Gottel,Jacob B. Gordon,Niki H. Learn,Laurence R. Gesquiere,Tim L. Wango,R. S. Mututua,J. Kinyua Warutere,Long'ida Siodi,Jack A. Gilbert,Luis B. Barreiro,Susan C. Alberts,Jenny Tung,Elizabeth A. Archie,Ran Blekhman +20 more
TL;DR: In this article, the authors leveraged 16,234 gut microbiome profiles, collected over 14 years from 585 wild baboons, to reveal that host genetic effects on the gut microbiome are nearly universal.
Journal ArticleDOI
Author Correction: Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project
E. A. Lopera-Maya,Alexander Kurilshikov,Adriaan van der Graaf,Shixian Hu,Sergio Andreu-Sánchez,Lianmin Chen,Arnau Vich Vila,Ranko Gacesa,Trishla Sinha,Valerie Collij,Marjolein A Y Klaassen,Laura A Bolte,M. F. B. Gois,Pieter B. Neerincx,Morris A. Swertz,Hermie J. M. Harmsen,Cisca Wijmenga,Jingyuan Fu,Rinse K. Weersma,Alexandra Zhernakova,Serena Sanna +20 more
TL;DR: In this paper , a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project was performed.
Journal ArticleDOI
Microbial Community Heterogeneity Within Colorectal Neoplasia and its Correlation With Colorectal Carcinogenesis.
Weixin Liu,Xiang Zhang,Hongzhi Xu,Shengmian Li,Harry Cheuk Hay Lau,Qiongyun Chen,Bin Zhang,Liuyang Zhao,Huarong Chen,Joseph J.Y. Sung,Jun Yu +10 more
TL;DR: In this article, the authors used 16S ribosomal RNA gene sequencing to determine the microbial community architecture within a colorectal cancer (CRC) or adenoma (n = 36) and the contribution of the intratumoral microbiota and its association with CRC progression remain elusive.
References
More filters
Journal ArticleDOI
The SILVA ribosomal RNA gene database project: improved data processing and web-based tools
Christian Quast,Elmar Pruesse,Pelin Yilmaz,Jan Gerken,Timmy Schweer,Pablo Yarza,Jörg Peplies,Frank Oliver Glöckner +7 more
TL;DR: The extensively curated SILVA taxonomy and the new non-redundant SILVA datasets provide an ideal reference for high-throughput classification of data from next-generation sequencing approaches.
Journal ArticleDOI
A global reference for human genetic variation.
Adam Auton,Gonçalo R. Abecasis,David Altshuler,Richard Durbin,David R. Bentley,Aravinda Chakravarti,Andrew G. Clark,Peter Donnelly,Evan E. Eichler,Paul Flicek,Stacey Gabriel,Richard A. Gibbs,Eric D. Green,Matthew E. Hurles,Bartha Maria Knoppers,Jan O. Korbel,Eric S. Lander,Charles Lee,Hans Lehrach,Elaine R. Mardis,Gabor T. Marth,Gil McVean,Deborah A. Nickerson,Jeanette Schmidt,Stephen T. Sherry,Jun Wang,Richard K. Wilson,Eric Boerwinkle,Harsha Doddapaneni,Yi Han,Viktoriya Korchina,Christie Kovar,Sandra L. Lee,Donna M. Muzny,Jeffrey G. Reid,Yiming Zhu,Yuqi Chang,Qiang Feng,Qiang Feng,Xiaodong Fang,Xiaodong Fang,Xiaosen Guo,Xiaosen Guo,Min Jian,Min Jian,Hui Jiang,Hui Jiang,Xin Jin,Tianming Lan,Guoqing Li,Jingxiang Li,Yingrui Li,Shengmao Liu,Xiao Liu,Xiao Liu,Yao Lu,Xuedi Ma,Meifang Tang,Bo Wang,Guangbiao Wang,Honglong Wu,Renhua Wu,Xun Xu,Ye Yin,Dandan Zhang,Wenwei Zhang,Jiao Zhao,Meiru Zhao,Xiaole Zheng,Namrata Gupta,Neda Gharani,Lorraine Toji,Norman P. Gerry,Alissa M. Resch,Jonathan Barker,Laura Clarke,Laurent Gil,Sarah E. Hunt,Gavin Kelman,Eugene Kulesha,Rasko Leinonen,William M. McLaren,Rajesh Radhakrishnan,Asier Roa,Dmitriy Smirnov,Richard Smith,Ian Streeter,Anja Thormann,Iliana Toneva,Brendan Vaughan,Xiangqun Zheng-Bradley,Russell J. Grocock,Sean Humphray,Terena James,Zoya Kingsbury,Ralf Sudbrak,M. Albrecht,Vyacheslav Amstislavskiy,Tatiana A. Borodina,Matthias Lienhard,Florian Mertes,Marc Sultan,Bernd Timmermann,Marie-Laure Yaspo,Lucinda Fulton,Victor Ananiev,Zinaida Belaia,Dimitriy Beloslyudtsev,Nathan Bouk,Chao Chen,Deanna M. Church,Robert M. Cohen,Charles Cook,John Garner,Timothy Hefferon,Mikhail Kimelman,Chunlei Liu,John Lopez,Peter Meric,Chris O’Sullivan,Yuri Ostapchuk,Lon Phan,Sergiy Ponomarov,Valerie A. Schneider,Eugene Shekhtman,Karl Sirotkin,Douglas J. Slotta,Hua Zhang,Senduran Balasubramaniam,John Burton,Petr Danecek,Thomas M. Keane,Anja Kolb-Kokocinski,Shane A. McCarthy,James Stalker,Michael A. Quail,Christopher Davies,Jeremy Gollub,Teresa Webster,Brant Wong,Yiping Zhan,Christopher L. Campbell,Yu Kong,Anthony Marcketta,Fuli Yu,Lilian Antunes,Matthew N. Bainbridge,Aniko Sabo,Zhuoyi Huang,Lachlan J. M. Coin,Lin Fang,Lin Fang,Qibin Li,Zhenyu Li,Haoxiang Lin,Binghang Liu,Ruibang Luo,Haojing Shao,Haojing Shao,Yinlong Xie,Chen Ye,Chang Yu,Fan Zhang,Hancheng Zheng,Zhu Hongmei,Can Alkan,Elif Dal,Fatma Kahveci,Erik Garrison,Deniz Kural,Wan-Ping Lee,Wen Fung Leong,Michael Strömberg,Alistair Ward,Jiantao Wu,Mengyao Zhang,Mark J. Daly,Mark A. DePristo,Robert E. Handsaker,Robert E. Handsaker,Eric Banks,Gaurav Bhatia,Guillermo del Angel,Giulio Genovese,Heng Li,Seva Kashin,Seva Kashin,Steven A. McCarroll,Steven A. McCarroll,James Nemesh,Ryan Poplin,Seungtai Yoon,Jayon Lihm,Vladimir Makarov,Srikanth Gottipati,Alon Keinan,Juan L. Rodriguez-Flores,Tobias Rausch,Markus Hsi-Yang Fritz,Adrian M. Stütz,Kathryn Beal,Avik Datta,Javier Herrero,Graham R. S. Ritchie,Daniel R. Zerbino,Pardis C. Sabeti,Pardis C. Sabeti,Ilya Shlyakhter,Ilya Shlyakhter,Stephen F. Schaffner,Stephen F. Schaffner,Joseph J. Vitti,Joseph J. Vitti,David Neil Cooper,Edward V. Ball,Peter D. Stenson,Bret Barnes,Markus J. Bauer,R. Keira Cheetham,Anthony J. Cox,Michael A. Eberle,Scott Kahn,Lisa Murray,John F. Peden,Richard Shaw,Eimear E. Kenny,Mark A. Batzer,Miriam K. Konkel,Jerilyn A. Walker,Daniel G. MacArthur,Monkol Lek,Ralf Herwig,Li Ding,Daniel C. Koboldt,David E. Larson,Kai Ye,Simon Gravel,Anand Swaroop,Emily Y. Chew,Tuuli Lappalainen,Yaniv Erlich,Melissa Gymrek,Melissa Gymrek,Thomas Willems,Jared T. Simpson,Mark D. Shriver,Jeffrey A. Rosenfeld,Carlos Bustamante,Stephen B. Montgomery,Francisco M. De La Vega,Jake K. Byrnes,Andrew Carroll,Marianne K. DeGorter,Phil Lacroute,Brian K. Maples,Alicia R. Martin,Andrés Moreno-Estrada,Andrés Moreno-Estrada,Suyash Shringarpure,Fouad Zakharia,Eran Halperin,Eran Halperin,Yael Baran,Eliza Cerveira,Jaeho Hwang,Ankit Malhotra,Dariusz Plewczynski,Kamen Radew,Mallory Romanovitch,Chengsheng Zhang,Fiona Hyland,David Craig,Alexis Christoforides,Nils Homer,Tyler Izatt,Ahmet Kurdoglu,Shripad Sinari,Kevin Squire,Chunlin Xiao,Jonathan Sebat,Danny Antaki,Madhusudan Gujral,Amina Noor,Kenny Ye,Esteban G. Burchard,Ryan D. Hernandez,Christopher R. Gignoux,David Haussler,David Haussler,Sol Katzman,W. James Kent,Bryan Howie,Andres Ruiz-Linares,Emmanouil T. Dermitzakis,Emmanouil T. Dermitzakis,Scott E. Devine,Hyun Min Kang,Jeffrey M. Kidd,Thomas W. Blackwell,Sean Caron,Wei Chen,S. Emery,Lars G. Fritsche,Christian Fuchsberger,Goo Jun,Goo Jun,Bingshan Li,Robert H. Lyons,Chris Scheller,Carlo Sidore,Carlo Sidore,Carlo Sidore,Shiya Song,Elzbieta Sliwerska,Daniel Taliun,Adrian Tan,Ryan P. Welch,Mary Kate Wing,Xiaowei Zhan,Philip Awadalla,Philip Awadalla,Alan Hodgkinson,Yun Li,Xinghua Shi,Andrew Quitadamo,Gerton Lunter,Jonathan Marchini,Simon Myers,Claire Churchhouse,Olivier Delaneau,Olivier Delaneau,Anjali Gupta-Hinch,Warren W. Kretzschmar,Zamin Iqbal,Iain Mathieson,Androniki Menelaou,Androniki Menelaou,Andy Rimmer,Dionysia Kiara Xifara,Taras K. Oleksyk,Yunxin Fu,Xiaoming Liu,Momiao Xiong,Lynn B. Jorde,David J. Witherspoon,Jinchuan Xing,Brian L. Browning,Sharon R. Browning,Fereydoun Hormozdiari,Peter H. Sudmant,Ekta Khurana,Chris Tyler-Smith,Cornelis A. Albers,Qasim Ayub,Yuan Chen,Vincenza Colonna,Vincenza Colonna,Luke Jostins,Klaudia Walter,Yali Xue,Mark Gerstein,Alexej Abyzov,Suganthi Balasubramanian,Jieming Chen,Declan Clarke,Yao Fu,Arif Harmanci,Mike Jin,Dong-Hoon Lee,Jeremy Liu,Xinmeng Jasmine Mu,Xinmeng Jasmine Mu,Jing Zhang,Yan Zhang,Christopher Hartl,Khalid Shakir,Jeremiah D. Degenhardt,Sascha Meiers,Benjamin Raeder,Francesco Paolo Casale,Oliver Stegle,Eric-Wubbo Lameijer,Ira M. Hall,Vineet Bafna,Jacob J. Michaelson,Eugene J. Gardner,Ryan E. Mills,Gargi Dayama,Ken Chen,Xian Fan,Zechen Chong,Tenghui Chen,Mark Chaisson,John Huddleston,Maika Malig,Bradley J. Nelson,Nicholas F. Parrish,Ben Blackburne,Sarah J. Lindsay,Zemin Ning,Yujun Zhang,Hugo Y. K. Lam,Cristina Sisu,Danny Challis,Uday S. Evani,James T. Lu,Uma Nagaswamy,Jin Yu,Wangshen Li,Lukas Habegger,Haiyuan Yu,Fiona Cunningham,Ian Dunham,Kasper Lage,Kasper Lage,Jakob Berg Jespersen,Jakob Berg Jespersen,Jakob Berg Jespersen,Heiko Horn,Heiko Horn,Donghoon Kim,Rob DeSalle,Apurva Narechania,Melissa A. Wilson Sayres,Fernando L. Mendez,G. David Poznik,Peter A. Underhill,David Mittelman,Ruby Banerjee,Maria Cerezo,Thomas W. Fitzgerald,Sandra Louzada,Andrea Massaia,Fengtang Yang,Divya Kalra,Walker Hale,Xu Dan,Kathleen C. Barnes,Christine Beiswanger,Hongyu Cai,Hongzhi Cao,Hongzhi Cao,Brenna M. Henn,Danielle Jones,Jane Kaye,Alastair Kent,Angeliki Kerasidou,Rasika A. Mathias,Pilar N. Ossorio,Michael Parker,Charles N. Rotimi,Charmaine D.M. Royal,Karla Sandoval,Yeyang Su,Zhongming Tian,Sarah A. Tishkoff,Marc Via,Yuhong Wang,Huanming Yang,Ling Yang,Jiayong Zhu,Walter F. Bodmer,Gabriel Bedoya,Zhiming Cai,Yang Gao,Jiayou Chu,Leena Peltonen,Andrés C. García-Montero,Alberto Orfao,Julie Dutil,Juan Carlos Martínez-Cruzado,R. Mathias,Anselm Hennis,Harold Watson,Colin A. McKenzie,Firdausi Qadri,Regina C. LaRocque,Xiaoyan Deng,Danny Asogun,Onikepe A. Folarin,Christian T. Happi,Omonwunmi Omoniwa,Matt Stremlau,Matt Stremlau,Ridhi Tariyal,Ridhi Tariyal,M Jallow,M Jallow,Fatoumatta Sisay Joof,Fatoumatta Sisay Joof,Tumani Corrah,Tumani Corrah,Kirk A. Rockett,Kirk A. Rockett,Dominic P. Kwiatkowski,Dominic P. Kwiatkowski,Jaspal S. Kooner,Tran Tinh Hien,Sarah J. Dunstan,Sarah J. Dunstan,Nguyen ThuyHang,Richard Fonnie,Robert F. Garry,Lansana Kanneh,Lina M. Moses,John S. Schieffelin,Donald S. Grant,Carla Gallo,Giovanni Poletti,Danish Saleheen,Asif Rasheed,Lisa D. Brooks,Adam Felsenfeld,Jean E. McEwen,Yekaterina Vaydylevich,Audrey Duncanson,Michael Dunn,Jeffery A. Schloss +517 more
TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
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A metagenome-wide association study of gut microbiota in type 2 diabetes
Junjie Qin,Yingrui Li,Zhiming Cai,Shenghui Li,Jianfeng Zhu,Fan Zhang,Suisha Liang,Wenwei Zhang,Yuanlin Guan,Dongqian Shen,Yangqing Peng,Dongya Zhang,Zhuye Jie,Wenxian Wu,Youwen Qin,Wenbin Xue,Junhua Li,Lingchuan Han,Donghui Lu,Peixian Wu,Yali Dai,Xiaojuan Sun,Zesong Li,Aifa Tang,Shilong Zhong,Xiaoping Li,Weineng Chen,Ran Xu,Mingbang Wang,Qiang Feng,Meihua Gong,Jing Yu,Yanyan Zhang,Ming Zhang,Torben Hansen,Gaston Sanchez,Jeroen Raes,Gwen Falony,Shujiro Okuda,Mathieu Almeida,Emmanuelle Le-chatelier,Pierre Renault,Nicolas Pons,Jean-Michel Batto,Zhaoxi Zhang,Hua Chen,Ruifu Yang,Wei-Mou Zheng,Songgang Li,Huanming Yang,Jian Wang,S. Dusko Ehrlich,Rasmus Nielsen,Oluf Pedersen,Oluf Pedersen,Karsten Kristiansen,Jun Wang +56 more
TL;DR: MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance.
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The Ribosomal Database Project: improved alignments and new tools for rRNA analysis
James R. Cole,Qiong Wang,Erick Cardenas,Jordan A. Fish,Benli Chai,Ryan J. Farris,A. S. Kulam-Syed-Mohideen,Donna M. McGarrell,Terry L. Marsh,George M. Garrity,James M. Tiedje +10 more
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The combination of estimates from different experiments.
TL;DR: The problem of making a combined estimate has been discussed previously by Cochran and Yates and Cochran (1937) for agricultural experiments, and by Bliss (1952) for bioassays in different laboratories as discussed by the authors.
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