Genome-Wide Association Study of Circulating Interleukin 6 Levels Identifies Novel Loci
Tarunveer S. Ahluwalia,Tarunveer S. Ahluwalia,Bram P. Prins,Mohammadreza Abdollahi,Nicola J. Armstrong,Stella Aslibekyan,L. Bain,Barbara J. Jefferis,Jens Baumert,Marian Beekman,Yoav Ben-Shlomo,Joshua C. Bis,Braxton D. Mitchell,Eco J. C. de Geus,Eco J. C. de Geus,Graciela E. Delgado,Diana Marek,Joel Eriksson,Eero Kajantie,Eero Kajantie,Stavroula Kanoni,John P. Kemp,John P. Kemp,Chen Lu,Riccardo E. Marioni,Stela McLachlan,Yuri Milaneschi,Ilja M. Nolte,Alexandros M. Petrelis,Eleonora Porcu,Maria Sabater-Lleal,Elnaz Naderi,Ilkka Seppälä,Tina Shah,Gaurav Singhal,Marie Standl,Alexander Teumer,Anbupalam Thalamuthu,Elisabeth Thiering,Stella Trompet,Christie M. Ballantyne,Emelia J. Benjamin,Juan P. Casas,Catherine Toben,George Dedoussis,Joris Deelen,Joris Deelen,Peter Durda,Jorgen Engmann,Mary F. Feitosa,Harald Grallert,Ann Hammarstedt,Sarah E. Harris,Georg Homuth,Jouke-Jan Hottenga,Jouke-Jan Hottenga,Sirpa Jalkanen,Yalda Jamshidi,Magdalene C. Jawahar,Tine Jess,Mika Kivimäki,Marcus E. Kleber,Jari Lahti,Jari Lahti,Yongmei Liu,Pedro Marques-Vidal,Dan Mellström,Simon P. Mooijaart,Martina Müller-Nurasyid,Brenda W.J.H. Penninx,Joana A. Revez,Peter Rossing,Peter Rossing,Katri Räikkönen,Naveed Sattar,Hubert Scharnagl,Bengt Sennblad,Bengt Sennblad,Angela Silveira,Beate St Pourcain,Beate St Pourcain,Beate St Pourcain,Nicholas J. Timpson,Julian N. Trollor,Jenny van Dongen,Jenny van Dongen,Diana van Heemst,Sophie Visvikis-Siest,Peter Vollenweider,Uwe Völker,Melanie Waldenberger,Gonneke Willemsen,Gonneke Willemsen,Delilah Zabaneh,Richard W Morris,Donna K. Arnett,Bernhard T. Baune,Bernhard T. Baune,Bernhard T. Baune,Dorret I. Boomsma,Dorret I. Boomsma,Yen Pei C. Chang,Ian J. Deary,Panos Deloukas,Johan G. Eriksson,Johan G. Eriksson,David M. Evans,David M. Evans,Manuel A. R. Ferreira,Tom R. Gaunt,Vilmundur Gudnason,Anders Hamsten,Joachim Heinrich,Joachim Heinrich,Aroon D. Hingorani,Steve E. Humphries,J. Wouter Jukema,Wolfgang Koenig,Wolfgang Koenig,Meena Kumari,Meena Kumari,Zoltán Kutalik,Zoltán Kutalik,Debbie A Lawlor,Terho Lehtimäki,Winfried März,Winfried März,Winfried März,Karen A. Mather,Karen A. Mather,Silvia Naitza,Matthias Nauck,Claes Ohlsson,Jackie F. Price,Olli T. Raitakari,Olli T. Raitakari,Kenneth Rice,Perminder S. Sachdev,Eline Slagboom,Eline Slagboom,Thorkild I. A. Sørensen,Tim D. Spector,David Stacey,Maria G. Stathopoulou,Toshiko Tanaka,S. Goya Wannamethee,Peter H. Whincup,Jerome I. Rotter,Abbas Dehghan,Eric Boerwinkle,Eric Boerwinkle,Bruce M. Psaty,Harold Snieder,Behrooz Z. Alizadeh +153 more
TLDR
This article conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67,428 individuals of European ancestry.Abstract:
Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.read more
Citations
More filters
Journal ArticleDOI
Interleukin 6 in diabetes, chronic kidney disease, and cardiovascular disease: mechanisms and therapeutic perspectives
TL;DR: In this paper , a review of the current understanding of how anti-inflammatory intervention via inhibition of the pro-inflammatory but pleiotropic cytokine interleukin (IL) 6 may benefit patients with these or related diseases or complications is presented.
Journal ArticleDOI
Multifaceted roles of IL-38 in inflammation and cancer.
TL;DR: A review of the current knowledge of IL-38 biology can be found in this article , where the authors discuss persistent controversies surrounding this cytokine, and highlight some questions to be addressed to facilitate progress towards a better understanding of its mechanisms of action.
Journal ArticleDOI
Body Mass Index, Interleukin-6 Signaling and Multiple Sclerosis: A Mendelian Randomization Study
TL;DR: IL-6 signaling was identified as a major mediator of the association between BMI and risk of MS and will help improve the understanding of MS biology and potentially lead to improved opportunities for targeted prevention strategies.
Journal ArticleDOI
Dissecting the IL‐6 pathway in cardiometabolic disease: A Mendelian randomization study on both <i>IL6</i> and <i>IL6R</i>
TL;DR: In this article , the authors compared the effects of targeting IL-6 and IL6 receptor on cardiometabolic risk and potential side effects and concluded that targeting either IL6 or IL6R may result in similar effects on CVD and adverse events.
Journal ArticleDOI
A Mendelian randomization study investigating the causal role of inflammation on Parkinson’s disease
Daniele Bottigliengo,Luisa Foco,Philip Seibler,Christine Klein,Inke R. König,Fabiola Del Greco M +5 more
TL;DR: The findings of this study suggest that the pro-inflammatory activity of the interleukin-6 cytokine could be a determinant of prodromal Parkinson’s disease.
References
More filters
Journal ArticleDOI
PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
Shaun Purcell,Shaun Purcell,Benjamin M. Neale,Benjamin M. Neale,Kathe Todd-Brown,Lori Thomas,Manuel A. R. Ferreira,David Bender,David Bender,Julian Maller,Julian Maller,Pamela Sklar,Pamela Sklar,Paul I.W. de Bakker,Paul I.W. de Bakker,Mark J. Daly,Mark J. Daly,Pak C. Sham +17 more
TL;DR: This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.
Journal ArticleDOI
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
TL;DR: The ANNOVAR tool to annotate single nucleotide variants and insertions/deletions, such as examining their functional consequence on genes, inferring cytogenetic bands, reporting functional importance scores, finding variants in conserved regions, or identifying variants reported in the 1000 Genomes Project and dbSNP is developed.
Journal ArticleDOI
The variant call format and VCFtools
Petr Danecek,Adam Auton,Gonçalo R. Abecasis,Cornelis A. Albers,Eric Banks,Mark A. DePristo,Robert E. Handsaker,Gerton Lunter,Gabor T. Marth,Stephen T. Sherry,Gilean McVean,Richard Durbin +11 more
TL;DR: VCFtools is a software suite that implements various utilities for processing VCF files, including validation, merging, comparing and also provides a general Perl API.
Journal ArticleDOI
NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins
TL;DR: The National Center for Biotechnology Information Reference Sequence (RefSeq) database provides a non-redundant collection of sequences representing genomic data, transcripts and proteins that pragmatically includes sequence data that are currently publicly available in the archival databases.
Journal ArticleDOI
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease
Luke Jostins,Stephan Ripke,Rinse K. Weersma,Richard H. Duerr,Dermot P.B. McGovern,Ken Y. Hui,James Lee,L. Philip Schumm,Yashoda Sharma,Carl A. Anderson,Jonah Essers,Mitja Mitrovic,Kaida Ning,Isabelle Cleynen,Emilie Theatre,Sarah L. Spain,Soumya Raychaudhuri,Philippe Goyette,Zhi Wei,Clara Abraham,Jean-Paul Achkar,Tariq Ahmad,Leila Amininejad,Ashwin N. Ananthakrishnan,Vibeke Andersen,Jane M. Andrews,Leonard Baidoo,Tobias Balschun,Peter A. Bampton,Alain Bitton,Gabrielle Boucher,Stephan Brand,Carsten Büning,Ariella Cohain,Sven Cichon,Mauro D'Amato,Dirk De Jong,Kathy L Devaney,Marla Dubinsky,Cathryn Edwards,David Ellinghaus,Lynnette R. Ferguson,Denis Franchimont,Karin Fransen,Richard B. Gearry,Michel Georges,Christian Gieger,Jürgen Glas,Talin Haritunians,Ailsa Hart,Christopher J. Hawkey,Matija Hedl,Xinli Hu,Tom H. Karlsen,Limas Kupčinskas,Subra Kugathasan,Anna Latiano,Debby Laukens,Ian C. Lawrance,Charlie W. Lees,Edouard Louis,Gillian Mahy,John C. Mansfield,Angharad R. Morgan,Craig Mowat,William G. Newman,Orazio Palmieri,Cyriel Y. Ponsioen,Uroš Potočnik,Natalie J. Prescott,Miguel Regueiro,Jerome I. Rotter,Richard K Russell,Jeremy D. Sanderson,Miquel Sans,Jack Satsangi,Stefan Schreiber,Lisa A. Simms,Jurgita Sventoraityte,Stephan R. Targan,Kent D. Taylor,Mark Tremelling,Hein W. Verspaget,Martine De Vos,Cisca Wijmenga,David C. Wilson,Juliane Winkelmann,Ramnik J. Xavier,Sebastian Zeissig,Bin Zhang,Clarence K. Zhang,Hongyu Zhao,Mark S. Silverberg,Vito Annese,Hakon Hakonarson,Steven R. Brant,Graham L. Radford-Smith,Christopher G. Mathew,John D. Rioux,Eric E. Schadt,Mark J. Daly,Andre Franke,Miles Parkes,Severine Vermeire,Jeffrey C. Barrett,Judy H. Cho +105 more
TL;DR: A meta-analysis of Crohn’s disease and ulcerative colitis genome-wide association scans is undertaken, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls.