Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
Phuwanat Sakornsakolpat,Phuwanat Sakornsakolpat,Dmitry Prokopenko,Dmitry Prokopenko,Maxime Lamontagne,Nicola F. Reeve,Anna L. Guyatt,Victoria E. Jackson,Nick Shrine,Dandi Qiao,Traci M. Bartz,Deog Kyeom Kim,Mi Kyeong Lee,Jeanne C. Latourelle,Xingnan Li,Jarrett D. Morrow,Ma'en Obeidat,Annah B. Wyss,Per Bakke,R. Graham Barr,Terri H. Beaty,Steven A. Belinsky,Guy Brusselle,Guy Brusselle,James D. Crapo,Kim de Jong,Dawn L. DeMeo,Tasha E. Fingerlin,Sina A. Gharib,Amund Gulsvik,Ian P. Hall,Ian P. Hall,John E. Hokanson,Woo Jin Kim,David A. Lomas,Stephanie J. London,Deborah A. Meyers,George T. O'Connor,Stephen I. Rennard,Stephen I. Rennard,David A. Schwartz,Pawel Sliwinski,David Sparrow,David P. Strachan,Ruth Tal-Singer,Yohannes Tesfaigzi,Jørgen Vestbo,Judith M. Vonk,Jae-Joon Yim,Xiaobo Zhou,Yohan Bossé,Ani Manichaikul,Lies Lahousse,Lies Lahousse,Edwin K. Silverman,H. Marike Boezen,Louise V. Wain,Louise V. Wain,Martin D. Tobin,Martin D. Tobin,Brian D. Hobbs,Michael H. Cho +61 more
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TLDR
This paper performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium and identified 82 loci associated with P < 5'×'10'8; 47 of these were previously described in association with either COPD or population-based measures of lung function.Abstract:
Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.read more
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The genetic architecture of type 2 diabetes
Christian Fuchsberger,Jason Flannick,Tanya M. Teslovich,Anubha Mahajan,Vineeta Agarwala,Kyle J. Gaulton,Clement Ma,Pierre Fontanillas,Loukas Moutsianas,Davis J. McCarthy,Manuel A. Rivas,John R. B. Perry,Xueling Sim,Thomas W. Blackwell,Neil Robertson,N. William Rayner,Pablo Cingolani,Adam E. Locke,Juan Fernandez Tajes,Heather M. Highland,Josée Dupuis,Peter S. Chines,Cecilia M. Lindgren,Christopher Hartl,Anne U. Jackson,Han Chen,Jeroen R. Huyghe,Martijn van de Bunt,Richard D. Pearson,Ashok Kumar,Martina Mueller-Nurasyid,Niels Grarup,Heather M. Stringham,Eric R. Gamazon,Jae-Hoon Lee,Yi Chen,Robert A. Scott,Jennifer E. Below,Peng Chen,Jinyan Huang,Min Jin Go,Michael L. Stitzel,Dorota Pasko,Stephen C. J. Parker,Tibor V. Varga,Todd Green,Nicola L. Beer,Aaron G. Day-Williams,Teresa Ferreira,Tasha E. Fingerlin,Momoko Horikoshi,Cheng Hu,Iksoo Huh,Mohammad Kamran Ikram,Bong-Jo Kim,Yongkang Kim,Young-Jin Kim,Min-Seok Kwon,Juyoung Lee,Selyeong Lee,Keng-Han Lin,Taylor J. Maxwell,Yoshihiko Nagai,Xu Wang,Ryan P. Welch,Joon Yoon,Weihua Zhang,Nir Barzilai,Benjamin F. Voight,Bok-Ghee Han,Christopher P. Jenkinson,Teemu Kuulasmaa,Johanna Kuusisto,Alisa K. Manning,Maggie C.Y. Ng,Nicholette D. Palmer,Beverley Balkau,Alena Stančáková,Hanna E. Abboud,Heiner Boeing,Vilmantas Giedraitis,Dorairaj Prabhakaran,Omri Gottesman,James Scott,Jason Carey,Phoenix Kwan,George B. Grant,Joshua D. Smith,Benjamin M. Neale,Shaun Purcell,Adam S. Butterworth,Joanna M. M. Howson,Heung Man Lee,Yingchang Lu,Soo Heon Kwak,Wei Zhao,John Danesh,Vincent K. L. Lam,Kyong Soo Park,Danish Saleheen,Wing-Yee So,Claudia H. T. Tam,Uzma Afzal,David Aguilar,Rector Arya,Tin Aung,Edmund Chan,Carmen Navarro,Ching-Yu Cheng,Domenico Palli,Adolfo Correa,Joanne E. Curran,Denis Rybin,Vidya S. Farook,Sharon P. Fowler,Barry I. Freedman,Michael Griswold,Daniel E. Hale,Pamela J. Hicks,Chiea Chuen Khor,Satish Kumar,Benjamin Lehne,Dorothée Thuillier,Wei-Yen Lim,Jianjun Liu,Yvonne T. van der Schouw,Marie Loh,Solomon K. Musani,Sobha Puppala,William R. Scott,Loic Yengo,Sian-Tsung Tan,Herman A. Taylor,Farook Thameem,Gregory P. Wilson,Tien Yin Wong,Pål R. Njølstad,Jonathan C. Levy,Massimo Mangino,Lori L. Bonnycastle,Thomas Schwarzmayr,João Fadista,Gabriela L. Surdulescu,Christian Herder,Christopher J. Groves,Thomas Wieland,Jette Bork-Jensen,Ivan Brandslund,Cramer Christensen,Heikki A. Koistinen,Alex S. F. Doney,Leena Kinnunen,Tõnu Esko,Andrew Farmer,Liisa Hakaste,Dylan Hodgkiss,Jasmina Kravic,Valeriya Lyssenko,Mette Hollensted,Marit E. Jørgensen,Torben Jørgensen,Claes Ladenvall,Johanne Marie Justesen,Annemari Käräjämäki,Jennifer Kriebel,Wolfgang Rathmann,Lars Lannfelt,Torsten Lauritzen,Narisu Narisu,Allan Linneberg,Olle Melander,Lili Milani,Matt Neville,Marju Orho-Melander,Lu Qi,Qibin Qi,Michael Roden,Olov Rolandsson,Amy J. Swift,Anders Rosengren,Kathleen Stirrups,Andrew R. Wood,Evelin Mihailov,Christine Blancher,Mauricio O. Carneiro,Jared Maguire,Ryan Poplin,Khalid Shakir,Timothy R. Fennell,Mark A. DePristo,Martin Hrabé de Angelis,Panos Deloukas,Anette P. Gjesing,Goo Jun,Peter M. Nilsson,Jacquelyn Murphy,Robert C. Onofrio,Barbara Thorand,Torben Hansen,Christa Meisinger,Frank B. Hu,Bo Isomaa,Fredrik Karpe,Liming Liang,Annette Peters,Cornelia Huth,Stephen O'Rahilly,Colin N. A. Palmer,Oluf Pedersen,Rainer Rauramaa,Jaakko Tuomilehto,Veikko Salomaa,Richard M. Watanabe,Ann-Christine Syvänen,Richard N. Bergman,Dwaipayan Bharadwaj,Erwin P. Bottinger,Yoon Shin Cho,Giriraj R. Chandak,Juliana C.N. Chan,Kee Seng Chia,Mark J. Daly,Shah Ebrahim,Claudia Langenberg,Paul Elliott,Kathleen A. Jablonski,Donna M. Lehman,Weiping Jia,Ronald C.W. Ma,Toni I. Pollin,Manjinder S. Sandhu,Nikhil Tandon,Philippe Froguel,Inês Barroso,Yik Ying Teo,Eleftheria Zeggini,Ruth J. F. Loos,Kerrin S. Small,Janina S. Ried,Ralph A. DeFronzo,Harald Grallert,Benjamin Glaser,Andres Metspalu,Nicholas J. Wareham,Mark Walker,Eric Banks,Christian Gieger,Erik Ingelsson,Hae Kyung Im,Thomas Illig,Paul W. Franks,Gemma Buck,Joseph Trakalo,David Buck,Inga Prokopenko,Reedik Mägi,Lars Lind,Yossi Farjoun,Katharine R. Owen,Anna L. Gloyn,Konstantin Strauch,Tiinamaija Tuomi,Jaspal S. Kooner,Jong-Young Lee,Taesung Park,Peter Donnelly,Andrew D. Morris,Andrew T. Hattersley,Donald W. Bowden,Francis S. Collins,Gil Atzmon,John C. Chambers,Tim D. Spector,Markku Laakso,Tim M. Strom,Graeme I. Bell,John Blangero,Ravindranath Duggirala,E. Shyong Tai,Gilean McVean,Craig L. Hanis,James G. Wilson,Mark Seielstad,Timothy M. Frayling,James B. Meigs,Nancy J. Cox,Robert Sladek,Eric S. Lander,Stacey Gabriel,Noël P. Burtt,Karen L. Mohlke,Thomas Meitinger,Leif Groop,Gonçalo R. Abecasis,Jose C. Florez,Laura J. Scott,Andrew P. Morris,Hyun Min Kang,Michael Boehnke,David Altshuler,Mark I. McCarthy +300 more
TL;DR: Large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes, but most fell within regions previously identified by genome-wide association studies.
Journal ArticleDOI
Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis.
Richard J. Allen,Beatriz Guillen-Guio,Justin M. Oldham,Shwu-Fan Ma,Amy Dressen,Megan L. Paynton,Luke M. Kraven,Ma'en Obeidat,Xuan Li,Michael Ng,Rebecca Braybrooke,Maria Molina-Molina,Maria Molina-Molina,Brian D. Hobbs,Rachel K. Putman,Phuwanat Sakornsakolpat,Helen Booth,William A. Fahy,Simon P. Hart,Michael Hill,Nik Hirani,Richard Hubbard,Robin J. McAnulty,Ann B. Millar,Vidyia Navaratnam,Eunice Oballa,Helen Parfrey,Gauri Saini,Moira K. B. Whyte,Yingze Zhang,Naftali Kaminski,Ayodeji Adegunsoye,Mary E. Strek,Margaret Neighbors,Xuting R. Sheng,Gunnar Gudmundsson,Vilmundur Gudnason,Hiroto Hatabu,David J. Lederer,Ani Manichaikul,John D. Newell,John D. Newell,George T. O'Connor,George T. O'Connor,Victor E. Ortega,Hanfei Xu,Tasha E. Fingerlin,Yohan Bossé,Ke Hao,Philippe Joubert,David C. Nickle,Don D. Sin,Wim Timens,Wim Timens,Dominic Furniss,Andrew P. Morris,Andrew P. Morris,Krina T. Zondervan,Ian P. Hall,Ian P. Hall,Ian Sayers,Ian Sayers,Martin D. Tobin,Martin D. Tobin,Toby M. Maher,Toby M. Maher,Michael H. Cho,Gary M. Hunninghake,David A. Schwartz,Brian L. Yaspan,Philip L. Molyneaux,Philip L. Molyneaux,Carlos Flores,Imre Noth,R. Gisli Jenkins,R. Gisli Jenkins,Louise V. Wain,Louise V. Wain +77 more
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Airway inflammation in COPD: progress to precision medicine
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A single-cell atlas of chromatin accessibility in the human genome
Kai Zhang,Kai Zhang,James D. Hocker,James D. Hocker,Michael Miller,Xiaomeng Hou,Joshua Chiou,Olivier Poirion,Yunjiang Qiu,Yang Eric Li,Yang Eric Li,Kyle J. Gaulton,Allen Wang,Sebastian Preissl,Bing Ren +14 more
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Recent advances in chronic obstructive pulmonary disease pathogenesis: from disease mechanisms to precision medicine.
Corry-Anke Brandsma,Maarten van den Berge,Tillie-Louise Hackett,Tillie-Louise Hackett,Guy Brusselle,Guy Brusselle,Wim Timens +6 more
TL;DR: Recent developments related to the abnormal inflammatory response, ECM and age‐related changes, structural changes in the small airways and the role of sex‐related differences are discussed, which are all relevant to explain the individual differences in the disease pathology of COPD and improve disease endotyping.
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