Genome-wide Association and Longitudinal Analyses Reveal Genetic Loci Linking Pubertal Height Growth, Pubertal Timing, and Childhood Adiposity
Diana L. Cousminer,Diane J. Berry,Nicholas J. Timpson,Wei Ang,Elisabeth Thiering,Enda M. Byrne,H. Rob Taal,Ville Huikari,Jonathan P. Bradfield,Marjan Kerkhof,Maria M. Groen-Blokhuis,Eskil Kreiner-Møller,Marcella Marinelli,Claus Holst,Jaakko T. Leinonen,John R. B. Perry,John R. B. Perry,John R. B. Perry,Ida Surakka,Olli Pietiläinen,Olli Pietiläinen,Johannes Kettunen,Verneri Anttila,Marika Kaakinen,Ulla Sovio,Anneli Pouta,Shikta Das,Vasiliki Lagou,Vasiliki Lagou,Chris Power,Inga Prokopenko,Inga Prokopenko,David M. Evans,John P. Kemp,John P. Kemp,Beate St Pourcain,Susan M. Ring,Aarno Palotie,Aarno Palotie,Aarno Palotie,Eero Kajantie,Clive Osmond,Terho Lehtimäki,Jorma Viikari,Mika Kähönen,Nicole M. Warrington,Stephen J. Lye,Lyle J. Palmer,Lyle J. Palmer,Carla M. T. Tiesler,Claudia Flexeder,Grant W. Montgomery,Sarah E. Medland,Albert Hofman,Hakon Hakonarson,Hakon Hakonarson,Hakon Hakonarson,Mònica Guxens,Meike Bartels,Veikko Salomaa,Joanne M. Murabito,Jaakko Kaprio,Jaakko Kaprio,Thorkild I. A. Sørensen,Thorkild I. A. Sørensen,Ferran Ballester,Hans Bisgaard,Dorret I. Boomsma,Gerard H. Koppelman,Struan F.A. Grant,Struan F.A. Grant,Struan F.A. Grant,Vincent W. V. Jaddoe,Nicholas G. Martin,Joachim Heinrich,Craig E. Pennell,Olli T. Raitakari,Johan G. Eriksson,George Davey Smith,Elina Hyppönen,Marjo-Riitta Järvelin,Mark I. McCarthy,Mark I. McCarthy,Mark I. McCarthy,Samuli Ripatti,Samuli Ripatti,Elisabeth Widen +86 more
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TLDR
This study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations, and uncovers part of the complex genetic architecture linking Pubertal height growth, the timing of puberty and childhood obesity.Abstract:
The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P 1.67 10(8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.read more
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Hundreds of variants clustered in genomic loci and biological pathways affect human height
Hana Lango Allen,Karol Estrada,Guillaume Lettre,Sonja I. Berndt,Michael N. Weedon,Fernando Rivadeneira,Cristen J. Willer,Anne U. Jackson,Sailaja Vedantam,Soumya Raychaudhuri,Teresa Ferreira,Andrew R. Wood,Robert J. Weyant,Ayellet V. Segrè,Elizabeth K. Speliotes,Eleanor Wheeler,Nicole Soranzo,Ju-Hyun Park,Jian Yang,Daniel F. Gudbjartsson,Nancy L. Heard-Costa,Joshua C. Randall,Lu Qi,Albert V. Smith,Reedik Maegi,Tomi Pastinen,Liming Liang,Iris M. Heid,Jian'an Luan,Gudmar Thorleifsson,Thomas W. Winkler,Michael E. Goddard,Ken Sin Lo,Cameron D. Palmer,Tsegaselassie Workalemahu,Yurii S. Aulchenko,Åsa Johansson,M. Carola Zillikens,Mary F. Feitosa,Tõnu Esko,Toby Johnson,Shamika Ketkar,Peter Kraft,Massimo Mangino,Inga Prokopenko,Devin Absher,Eva Albrecht,Florian Ernst,Nicole L. Glazer,Caroline Hayward,Jouke-Jan Hottenga,Kevin B. Jacobs,Joshua W. Knowles,Zoltán Kutalik,Keri L. Monda,Ozren Polasek,Michael Preuss,Nigel W. Rayner,Neil R. Robertson,Valgerdur Steinthorsdottir,Jonathan Tyrer,Benjamin F. Voight,Fredrik Wiklund,Jianfeng Xu,Jing Hua Zhao,Dale R. Nyholt,Niina Pellikka,Markus Perola,John R. B. Perry,Ida Surakka,Mari-Liis Tammesoo,Elizabeth L. Altmaier,Najaf Amin,Thor Aspelund,Tushar Bhangale,Gabrielle Boucher,Daniel I. Chasman,Constance Chen,Lachlan J. M. Coin,Mark E. Cooper,Anna L. Dixon,Quince Gibson,Elin Grundberg,Ke Hao,M. Juhani Junttila,Lee M. Kaplan,Johannes Kettunen,Inke R. Koenig,Tony Kwan,Robert Lawrence,Douglas F. Levinson,Mattias Lorentzon,Barbara McKnight,Andrew P. Morris,Martina Mueller,Julius S. Ngwa,Shaun Purcell,Suzanne Rafelt,Rany M. Salem,Erika Salvi,Serena Sanna,Jianxin Shi,Ulla Sovio,John R. Thompson,Michael C. Turchin,Liesbeth Vandenput,Dominique J. Verlaan,Veronique Vitart,Charles C. White,Andreas Ziegler,Peter Almgren,Anthony J. Balmforth,Harry Campbell,Lorena Citterio,Alessandro De Grandi,Anna F. Dominiczak,Jubao Duan,Paul Elliott,Roberto Elosua,Johan G. Eriksson,Nelson B. Freimer,Eco J. C. de Geus,Nicola Glorioso,Shen Haiqing,Anna-Liisa Hartikainen,Aki S. Havulinna,Andrew A. Hicks,Jennie Hui,Wilmar Igl,Thomas Illig,Antti Jula,Eero Kajantie,Tuomas O. Kilpelaeinen,Markku Koiranen,Ivana Kolcic,Seppo Koskinen,Peter Kovacs,Jaana Laitinen,Jianjun Liu,Marja-Liisa Lokki,Ana Marušić,Andrea Maschio,Thomas Meitinger,Antonella Mulas,Guillaume Paré,Alex N. Parker,John F. Peden,Astrid Petersmann,Irene Pichler,Kirsi H. Pietiläinen,Anneli Pouta,Martin Riddertrale,Jerome I. Rotter,Jennifer G. Sambrook,Alan R. Sanders,Carsten Oliver Schmidt,Juha Sinisalo,Jan Smit,Heather M. Stringham,G. Bragi Walters,Elisabeth Widen,Sarah H. Wild,Gonneke Willemsen,Laura Zagato,Lina Zgaga,Paavo Zitting,Helene Alavere,Martin Farrall,Wendy L. McArdle,Mari Nelis,Marjolein Peters,Samuli Ripatti,Joyce B. J. vVan Meurs,Katja K.H. Aben,Kristin G. Ardlie,Jacques S. Beckmann,John Beilby,Richard N. Bergman,Sven Bergmann,Francis S. Collins,Daniele Cusi,Martin den Heijer,Gudny Eiriksdottir,Pablo V. Gejman,Alistair S. Hall,Anders Hamsten,Heikki V. Huikuri,Carlos Iribarren,Mika Kähönen,Jaakko Kaprio,Sekar Kathiresan,Lambertus A. Kiemeney,Thomas D. Kocher,Lenore J. Launer,Terho Lehtimäki,Olle Melander,Thomas H. Mosley,Arthur W. Musk,Markku S. Nieminen,Christopher J. O'Donnell,Claes Ohlsson,Ben A. Oostra,Lyle J. Palmer,Olli T. Raitakari,Paul M. Ridker,John D. Rioux,Aila Rissanen,Carlo Rivolta,Heribert Schunkert,Alan R. Shuldiner,David S. Siscovick,Michael Stumvoll,Anke Toenjes,Jaakko Tuomilehto,Gert-Jan B. van Ommen,Jorma Viikari,Andrew C. Heath,Nicholas G. Martin,Grant W. Montgomery,Michael A. Province,Manfred Kayser,Alice M. Arnold,Larry D. Atwood,Eric Boerwinkle,Stephen J. Chanock,Panos Deloukas,Christian Gieger,Henrik Grönberg,Per Hall,Andrew T. Hattersley,Christian Hengstenberg,Wolfgang Hoffman,G. Mark Lathrop,Veikko Salomaa,Stefan Schreiber,Manuela Uda,Dawn M. Waterworth,Alan F. Wright,Themistocles L. Assimes,Inês Barroso,Albert Hofman,Karen L. Mohlke,Dorret I. Boomsma,Mark J. Caulfield,L. Adrienne Cupples,Jeanette Erdmann,Caroline S. Fox,Vilmundur Gudnason,Ulf Gyllensten,Tamara B. Harris,Richard B. Hayes,Marjo-Ritta Jarvelin,Vincent Mooser,Patricia B. Munroe,Willem H. Ouwehand,Brenda W.J.H. Penninx,Peter P. Pramstaller,Thomas Quertermous,Igor Rudan,Nilesh J. Samani,Tim D. Spector,Henry Voelzke,Hugh Watkins,James F. Wilson,Leif Groop,Talin Haritunians,Frank B. Hu,Robert C. Kaplan,Andres Metspalu,Kari E. North,David Schlessinger,Nicholas J. Wareham,David J. Hunter,Jeffrey R. O'Connell,David P. Strachan,H. Erich Schadt,Unnur Thorsteinsdottir,Leena Peltonen,André G. Uitterlinden,Peter M. Visscher,Nilanjan Chatterjee,Ruth J. F. Loos,Michael Boehnke,Mark I. McCarthy,Erik Ingelsson,Cecilia M. Lindgren,Gonçalo R. Abecasis,Kari Stefansson,Timothy M. Frayling,Joel N. Hirschhorn +289 more
TL;DR: In this paper, the authors show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait, revealing patterns with important implications for genetic studies of common human diseases and traits.
Conflict of interest statement. None declared.
TL;DR: It is found that women over 50 are more likely to have a family history of diabetes, especially if they are obese, than women under the age of 50.
Journal ArticleDOI
Sex-dependent dominance at a single locus maintains variation in age at maturity in salmon
Nicola J. Barson,Tutku Aykanat,Kjetil Hindar,Matthew Baranski,Geir H. Bolstad,Peder Fiske,Celeste Jacq,Arne Jensen,Susan E. Johnston,Sten Karlsson,Matthew Peter Kent,Thomas Moen,Eero Niemelä,Torfinn Nome,Tor F. Næsje,Panu Orell,Atso Romakkaniemi,Harald Sægrov,Kurt Urdal,Jaakko Erkinaro,Sigbjørn Lien,Craig R. Primmer +21 more
TL;DR: This work identifies a large effect locus controlling age at maturity in Atlantic salmon, an important fitness trait in which selection favours earlier maturation in males than females, and shows it is a clear example of sex-dependent dominance that reduces intralocus sexual conflict and maintains adaptive variation in wild populations.
Journal ArticleDOI
New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
Yingchang Lu,Felix R. Day,Stefan Gustafsson,Stefan Gustafsson,Martin L. Buchkovich,Jianbo Na,Veronique Bataille,Veronique Bataille,Diana L. Cousminer,Zari Dastani,Alexander W. Drong,Tõnu Esko,David M. Evans,Mario Falchi,Mario Falchi,Mary F. Feitosa,Teresa Ferreira,Åsa K. Hedman,Robin Haring,Robin Haring,Pirro G. Hysi,Mark M. Iles,Anne E. Justice,Stavroula Kanoni,Stavroula Kanoni,Vasiliki Lagou,Rui Li,Xin Li,Adam E. Locke,Chen Lu,Reedik Mägi,John R. B. Perry,Tune H. Pers,Qibin Qi,Marianna Sanna,Marianna Sanna,Ellen M. Schmidt,William R. Scott,William R. Scott,Dmitry Shungin,Dmitry Shungin,Alexander Teumer,Anna A. E. Vinkhuyzen,Ryan W. Walker,Harm-Jan Westra,Mingfeng Zhang,Weihua Zhang,Weihua Zhang,Jing Hua Zhao,Zhihong Zhu,Uzma Afzal,Uzma Afzal,Tarunveer S. Ahluwalia,Stephan J. L. Bakker,Claire Bellis,Amélie Bonnefond,Amélie Bonnefond,Katja Borodulin,Aron S. Buchman,Tommy Cederholm,Audrey C. Choh,Hyung Jin Choi,Joanne E. Curran,Lisette C. P. G. M. de Groot,Philip L. De Jager,Philip L. De Jager,Philip L. De Jager,Rosalie A. M. Dhonukshe-Rutten,Anke W. Enneman,Elodie Eury,Elodie Eury,Daniel S. Evans,Tom Forsén,Nele Friedrich,Frédéric Fumeron,Melissa E. Garcia,Simone Gärtner,Bok-Ghee Han,Aki S. Havulinna,Caroline Hayward,Dena G. Hernandez,Hans L. Hillege,Till Ittermann,Jack W. Kent,Ivana Kolcic,Tiina Laatikainen,Tiina Laatikainen,Jari Lahti,Irene Mateo Leach,Christine G. Lee,Christine G. Lee,Jong-Young Lee,Tian Liu,Youfang Liu,Stéphane Lobbens,Stéphane Lobbens,Marie Loh,Marie Loh,Leo-Pekka Lyytikäinen,Carolina Medina-Gomez,Karl Michaëlsson,Mike A. Nalls,Carrie M. Nielson,Laticia Oozageer,Laura Pascoe,Lavinia Paternoster,Ozren Polasek,Ozren Polasek,Samuli Ripatti,Samuli Ripatti,Mark A. Sarzynski,Chan Soo Shin,Nina Smolej Narančić,Dominik Spira,Priya Srikanth,Elisabeth Steinhagen-Thiessen,Yun Ju Sung,Karin M. A. Swart,Karin M. A. Swart,Leena Taittonen,Toshiko Tanaka,Emmi Tikkanen,Nathalie van der Velde,Natasja M. van Schoor,Natasja M. van Schoor,Niek Verweij,Alan F. Wright,Lei Yu,Joseph M. Zmuda,Niina Eklund,Terrence Forrester,Niels Grarup,Anne U. Jackson,Kati Kristiansson,Kati Kristiansson,Teemu Kuulasmaa,Johanna Kuusisto,Peter Lichtner,Jian'an Luan,Anubha Mahajan,Satu Männistö,Cameron D. Palmer,Cameron D. Palmer,Janina S. Ried,Robert A. Scott,Alena Stančáková,Peter Wagner,Peter Wagner,Ayse Demirkan,Angela Döring,Vilmundur Gudnason,Douglas P. Kiel,Brigitte Kühnel,Massimo Mangino,Barbara McKnight,Barbara McKnight,Cristina Menni,Jeffrey R. O'Connell,Ben A. Oostra,Alan R. Shuldiner,Alan R. Shuldiner,Kijoung Song,Liesbeth Vandenput,Cornelia M. van Duijn,Peter Vollenweider,Charles C. White,Michael Boehnke,Yvonne Boettcher,Richard S. Cooper,Nita G. Forouhi,Christian Gieger,Harald Grallert,Aroon D. Hingorani,Torben Jørgensen,Torben Jørgensen,Pekka Jousilahti,Mika Kivimäki,Meena Kumari,Markku Laakso,Claudia Langenberg,Allan Linneberg,Amy Luke,Colin A. McKenzie,Aarno Palotie,Aarno Palotie,Aarno Palotie,Oluf Pedersen,Annette Peters,Konstantin Strauch,Bamidele O. Tayo,Nicholas J. Wareham,David A. Bennett,Lars Bertram,Lars Bertram,John Blangero,Matthias Blüher,Claude Bouchard,Harry Campbell,Nam H. Cho,Steven R. Cummings,Stefan A. Czerwinski,Ilja Demuth,Rahel Eckardt,Johan G. Eriksson,Johan G. Eriksson,Luigi Ferrucci,Oscar H. Franco,Philippe Froguel,Philippe Froguel,Ron T. Gansevoort,Torben Hansen,Torben Hansen,Tamara B. Harris,Nicholas D. Hastie,Markku Heliövaara,Albert Hofman,Joanne M. Jordan,Antti Jula,Mika Kähönen,Eero Kajantie,Eero Kajantie,Eero Kajantie,Paul Knekt,Seppo Koskinen,Peter Kovacs,Terho Lehtimäki,Lars Lind,Yongmei Liu,Eric S. Orwoll,Clive Osmond,Markus Perola,Markus Perola,Louis Pérusse,Olli T. Raitakari,Olli T. Raitakari,Tuomo Rankinen,Dabeeru C. Rao,Treva Rice,Fernando Rivadeneira,Igor Rudan,Veikko Salomaa,Thorkild I. A. Sørensen,Michael Stumvoll,Anke Tönjes,Bradford Towne,Gregory J. Tranah,Angelo Tremblay,André G. Uitterlinden,Pim van der Harst,Erkki Vartiainen,Jorma S. A. Viikari,Veronique Vitart,Marie-Claude Vohl,Henry Völzke,Mark Walker,Mark Walker,Henri Wallaschofski,Sarah H Wild,James F. Wilson,Loic Yengo,Loic Yengo,D. Timothy Bishop,Ingrid B. Borecki,Ingrid B. Borecki,John C. Chambers,John C. Chambers,John C. Chambers,L. Adrienne Cupples,Abbas Dehghan,Panos Deloukas,Panos Deloukas,Panos Deloukas,Ghazaleh Fatemifar,Caroline S. Fox,Terrence S. Furey,Lude Franke,Jiali Han,David J. Hunter,Juha Karjalainen,Fredrik Karpe,Robert C. Kaplan,Jaspal S. Kooner,Jaspal S. Kooner,Jaspal S. Kooner,Mark I. McCarthy,Joanne M. Murabito,Andrew P. Morris,Andrew P. Morris,Julia A. Newton Bishop,Kari E. North,Claes Ohlsson,Ken K. Ong,Inga Prokopenko,J. Brent Richards,Eric E. Schadt,Tim D. Spector,Elisabeth Widen,Cristen J. Willer,Jian Yang,Erik Ingelsson,Erik Ingelsson,Erik Ingelsson,Karen L. Mohlke,Joel N. Hirschhorn,Joel N. Hirschhorn,Joel N. Hirschhorn,John Andrew Pospisilik,M. Carola Zillikens,Cecilia M. Lindgren,Tuomas O. Kilpeläinen,Tuomas O. Kilpeläinen,Ruth J. F. Loos +311 more
TL;DR: The loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Journal ArticleDOI
The Generation R Study: Biobank update 2015
Claudia J. Kruithof,Marjolein N. Kooijman,Cornelia M. van Duijn,Oscar H. Franco,Johan C. de Jongste,Caroline C W Klaver,Johan P. Mackenbach,Henriette A. Moll,Hein Raat,Edmond H. H. M. Rings,Fernando Rivadeneira,Eric A.P. Steegers,Henning Tiemeier,André G. Uitterlinden,Frank C. Verhulst,Eppo B. Wolvius,Albert Hofman,Vincent W. V. Jaddoe +17 more
TL;DR: Together with detailed phenotype measurements, these biological samples provide a unique resource for epidemiological studies focused on environmental exposures, genetic and genomic determinants and their interactions in relation to growth, health and development from fetal life onwards.
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
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
Paul Burton,David Clayton,Lon R. Cardon,Nicholas John Craddock,Panos Deloukas,Audrey Duncanson,Dominic P. Kwiatkowski,Mark I. McCarthy,Willem H. Ouwehand,Nilesh J. Samani,John A. Todd,Peter Donnelly,Jeffrey C. Barrett,Dan Davison,Doug Easton,David M. Evans,H. T. Leung,Jonathan Marchini,Andrew P. Morris,Chris C. A. Spencer,Martin D. Tobin,Antony P. Attwood,James P. Boorman,Barbara Cant,Ursula Everson,Judith M. Hussey,Jennifer Jolley,Alexandra S. Knight,Kerstin Koch,Elizabeth Meech,Sarah Nutland,Christopher Prowse,Helen Stevens,Niall C. Taylor,Graham R. Walters,Neil Walker,Nicholas A. Watkins,Thilo Winzer,Richard Jones,Wendy L. McArdle,Susan M. Ring,David P. Strachan,Marcus Pembrey,Gerome Breen,David St Clair,Sian Caesar,Katherine Gordon-Smith,Lisa Jones,Christine Fraser,Elaine K. Green,Detelina Grozeva,Marian L. Hamshere,Peter Holmans,Ian Jones,George Kirov,Valentina Moskvina,Ivan Nikolov,Michael Conlon O'Donovan,Michael John Owen,David A. Collier,Amanda Elkin,Anne Farmer,Richard Williamson,Peter McGuffin,Allan H. Young,I. Nicol Ferrier,Stephen G. Ball,Anthony J. Balmforth,Jennifer H. Barrett,D. Timothy Bishop,Mark M. Iles,Azhar Maqbool,Nadira Yuldasheva,Alistair S. Hall,Peter S. Braund,Richard J. Dixon,Massimo Mangino,Suzanne Stevens,John R. Thompson,Francesca Bredin,Mark Tremelling,Miles Parkes,Hazel E. Drummond,Charlie W. Lees,Elaine R. Nimmo,Jack Satsangi,Sheila A. Fisher,Alastair Forbes,Cathryn M. Lewis,Clive M. Onnie,Natalie J. Prescott,Jeremy D. Sanderson,Christopher G. Mathew,Jamie Barbour,M. Khalid Mohiuddin,Catherine E. Todhunter,John C. Mansfield,Tariq Ahmad,Fraser Cummings,Derek P. Jewell,John Webster,Morris J. Brown,G. Mark Lathrop,John M. C. Connell,Anna F. Dominiczak,Carolina A. Braga Marcano,Beverley Burke,Richard Dobson,Johannie Gungadoo,Kate L. Lee,Patricia B. Munroe,Stephen Newhouse,Abiodun Onipinla,Chris Wallace,Mingzhan Xue,Mark J. Caulfield,Martin Farrall,Anne Barton,Ian N. Bruce,Hannah Donovan,Steve Eyre,Paul D. Gilbert,Samantha L. Hider,Anne Hinks,Sally John,Catherine Potter,Alan J. Silman,Deborah P M Symmons,Wendy Thomson,Jane Worthington,David B. Dunger,Barry Widmer,Timothy M. Frayling,Rachel M. Freathy,Hana Lango,John R. B. Perry,Beverley M. Shields,Michael N. Weedon,Andrew T. Hattersley,Graham A. Hitman,Mark Walker,Kate S. Elliott,Christopher J. Groves,Cecilia M. Lindgren,Nigel W. Rayner,Nicholas J. Timpson,Eleftheria Zeggini,Melanie J. Newport,Giorgio Sirugo,Emily J. Lyons,Fredrik O. Vannberg,Adrian V. S. Hill,Linda A. Bradbury,C Farrar,J J Pointon,Paul Wordsworth,Matthew A. Brown,Jayne A. Franklyn,Joanne M. Heward,Matthew J. Simmonds,Stephen C. L. Gough,Sheila Seal,Michael R. Stratton,Nazneen Rahman,Maria Ban,An Goris,Stephen Sawcer,Alastair Compston,David J. Conway,Muminatou Jallow,Kirk A. Rockett,Suzannah Bumpstead,Amy Chaney,Kate Downes,Mohammed J. R. Ghori,Rhian Gwilliam,Sarah E. Hunt,Michael Inouye,Andrew Keniry,Emma King,Ralph McGinnis,Simon C. Potter,Rathi Ravindrarajah,Pamela Whittaker,Claire Widden,David Withers,Niall Cardin,Teresa Ferreira,Joanne Pereira-Gale,Ingileif B. Hallgrímsdóttir,Bryan Howie,Zhan Su,Yik Ying Teo,Damjan Vukcevic,David Bentley,A Compston +195 more
TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
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What is a randomised controlled trial
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The Wellcome Trust Case Control Consortium, U.K.
TL;DR: This article reports that the magazine's award for Research Leader of the Year was given to the Wellcome Trust Case Control Consortium which conducted a huge genetic study to look at the genetic causes for various diseases.
Journal ArticleDOI
A new multipoint method for genome-wide association studies by imputation of genotypes
TL;DR: This work proposes a coherent analysis framework that treats the genome-wide association problem as one involving missing or uncertain genotypes, and proposes a model-based imputation method for inferring genotypes at observed or unobserved SNPs, leading to improved power over existing methods for multipoint association mapping.
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Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche
John R. B. Perry,Felix R. Day,Cathy E. Elks,Patrick Sulem,Deborah J. Thompson,Teresa Ferreira,Chunyan He,Daniel I. Chasman,Tõnu Esko,Tõnu Esko,Gudmar Thorleifsson,Eva Albrecht,Wei Ang,Tanguy Corre,Tanguy Corre,Diana L. Cousminer,Bjarke Feenstra,Nora Franceschini,Andrea Ganna,Andrew D. Johnson,Sanela Kjellqvist,Kathryn L. Lunetta,George McMahon,Ilja M. Nolte,Lavinia Paternoster,Eleonora Porcu,Albert V. Smith,Lisette Stolk,Alexander Teumer,Natalia Tšernikova,Emmi Tikkanen,Sheila Ulivi,Erin K. Wagner,Najaf Amin,Laura J. Bierut,Enda M. Byrne,Enda M. Byrne,Jouke-Jan Hottenga,Daniel L. Koller,Massimo Mangino,Tune H. Pers,Tune H. Pers,Tune H. Pers,Laura M. Yerges-Armstrong,Jing Hua Zhao,Irene L. Andrulis,Hoda Anton-Culver,Femke Atsma,Stefania Bandinelli,Matthias W. Beckmann,Javier Benitez,Carl Blomqvist,Stig E. Bojesen,Manjeet K. Bolla,Bernardo Bonanni,Hiltrud Brauch,Hiltrud Brauch,Hermann Brenner,Julie E. Buring,Jenny Chang-Claude,Stephen J. Chanock,Jinhui Chen,Georgia Chenevix-Trench,J. Margriet Collée,Fergus J. Couch,David Couper,Andrea D. Coviello,Angela Cox,Kamila Czene,Adamo Pio D'Adamo,George Davey Smith,Immaculata De Vivo,Ellen W. Demerath,Joe Dennis,Peter Devilee,Aida Karina Dieffenbach,Alison M. Dunning,Gudny Eiriksdottir,Johan G. Eriksson,Johan G. Eriksson,Peter A. Fasching,Luigi Ferrucci,Dieter Flesch-Janys,Henrik Flyger,Tatiana Foroud,Lude Franke,Melissa E. Garcia,Montserrat Garcia-Closas,Frank Geller,Eco de Geus,Graham G. Giles,Graham G. Giles,Daniel F. Gudbjartsson,Daniel F. Gudbjartsson,Vilmundur Gudnason,Pascal Guénel,Suiqun Guo,Per Hall,Ute Hamann,Robin Haring,Catharina A. Hartman,Andrew C. Heath,Albert Hofman,Maartje J. Hooning,John L. Hopper,Frank B. Hu,David J. Hunter,David Karasik,Douglas P. Kiel,Julia A. Knight,Veli-Matti Kosma,Zoltán Kutalik,Zoltán Kutalik,Sandra Lai,Diether Lambrechts,Annika Lindblom,Reedik Mägi,Patrik K. E. Magnusson,Arto Mannermaa,Nicholas G. Martin,Gisli Masson,Patrick F. McArdle,Wendy L. McArdle,Mads Melbye,Mads Melbye,Kyriaki Michailidou,Evelin Mihailov,Lili Milani,Roger L. Milne,Roger L. Milne,Heli Nevanlinna,Patrick Neven,Ellen A. Nohr,Albertine J. Oldehinkel,Ben A. Oostra,Aarno Palotie,Aarno Palotie,Aarno Palotie,Munro Peacock,Nancy L. Pedersen,Paolo Peterlongo,Julian Peto,Paul D.P. Pharoah,Dirkje S. Postma,Anneli Pouta,Anneli Pouta,Katri Pylkäs,Paolo Radice,Susan M. Ring,Fernando Rivadeneira,Antonietta Robino,Lynda M. Rose,Anja Rudolph,Veikko Salomaa,Serena Sanna,David Schlessinger,Marjanka K. Schmidt,Mellissa C. Southey,Ulla Sovio,Ulla Sovio,Meir J. Stampfer,Doris Stöckl,Anna Maria Storniolo,Nicholas J. Timpson,Jonathan Tyrer,Jenny A. Visser,Peter Vollenweider,Henry Völzke,Gérard Waeber,Melanie Waldenberger,Henri Wallaschofski,Qin Wang,Gonneke Willemsen,Robert Winqvist,Bruce H. R. Wolffenbuttel,Margaret J. Wright,Dorret I. Boomsma,Michael J. Econs,Kay-Tee Khaw,Ruth J. F. Loos,Ruth J. F. Loos,Mark I. McCarthy,Grant W. Montgomery,John P. Rice,Elizabeth A. Streeten,Elizabeth A. Streeten,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Cornelia M. van Duijn,Behrooz Z. Alizadeh,Sven Bergmann,Sven Bergmann,Eric Boerwinkle,Heather A. Boyd,Laura Crisponi,Paolo Gasparini,Christian Gieger,Tamara B. Harris,Erik Ingelsson,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Peter Kraft,Debbie A Lawlor,Andres Metspalu,Craig E. Pennell,Paul M. Ridker,Harold Snieder,Thorkild I. A. Sørensen,Tim D. Spector,David P. Strachan,André G. Uitterlinden,Nicholas J. Wareham,Elisabeth Widen,Marek Zygmunt,Anna Murray,Douglas F. Easton,Kari Stefansson,Kari Stefansson,Joanne M. Murabito,Ken K. Ong +220 more
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
Cathy E. Elks,John R. B. Perry,Patrick Sulem,Daniel I. Chasman,Nora Franceschini,Chunyan He,Kathryn L. Lunetta,Kathryn L. Lunetta,Jenny A. Visser,Enda M. Byrne,Enda M. Byrne,Diana L. Cousminer,Daniel F. Gudbjartsson,Tõnu Esko,Bjarke Feenstra,Jouke-Jan Hottenga,Daniel L. Koller,Zoltán Kutalik,Zoltán Kutalik,Peng Lin,Massimo Mangino,Mara Marongiu,Patrick F. McArdle,Albert V. Smith,Lisette Stolk,Sophie H. Van Wingerden,Jing Hua Zhao,Eva Albrecht,Tanguy Corre,Erik Ingelsson,Caroline Hayward,Patrik K. E. Magnusson,Erin N. Smith,Erin N. Smith,S. Ulivi,Nicole M. Warrington,Lina Zgaga,Helen Alavere,Najaf Amin,Thor Aspelund,Stefania Bandinelli,Inês Barroso,Gerald S. Berenson,Sven Bergmann,Sven Bergmann,Hannah Blackburn,Eric Boerwinkle,Julie E. Buring,Fabio Busonero,Harry Campbell,Stephen J. Chanock,Wei Chen,Marilyn C. Cornelis,David Couper,Andrea D. Coviello,Pio D'Adamo,Ulf de Faire,Eco J. C. de Geus,Panos Deloukas,Angela Döring,George Davey Smith,Douglas F. Easton,Gudny Eiriksdottir,Valur Emilsson,Johan G. Eriksson,Johan G. Eriksson,Luigi Ferrucci,Aaron R. Folsom,Tatiana Foroud,Melissa E. Garcia,Paolo Gasparini,Frank Geller,Christian Gieger,Vilmundur Gudnason,Per Hall,Susan E. Hankinson,Liana Ferreli,Andrew C. Heath,Dena G. Hernandez,Albert Hofman,Frank B. Hu,Thomas Illig,Marjo-Riitta Järvelin,Andrew D. Johnson,David Karasik,Kay-Tee Khaw,Douglas P. Kiel,Tuomas O. Kilpelänen,Ivana Kolcic,Peter Kraft,Lenore J. Launer,Joop S.E. Laven,Shengxu Li,Jianjun Liu,Daniel Levy,Daniel Levy,Nicholas G. Martin,Wendy L. McArdle,Mads Melbye,Vincent Mooser,Jeffrey C. Murray,Sarah S. Murray,Sarah S. Murray,Mike A. Nalls,Pau Navarro,Mari Nelis,Andy R Ness,Kate Northstone,Ben A. Oostra,Munro Peacock,Lyle J. Palmer,Aarno Palotie,Aarno Palotie,Aarno Palotie,Guillaume Paré,Guillaume Paré,Alex Parker,Nancy L. Pedersen,Leena Peltonen,Craig E. Pennell,Paul D.P. Pharoah,Ozren Polasek,Andrew S. Plump,Anneli Pouta,Eleonora Porcu,Thorunn Rafnar,John P. Rice,Susan M. Ring,Fernando Rivadeneira,Igor Rudan,Igor Rudan,Cinzia Sala,Veikko Salomaa,Serena Sanna,David Schlessinger,Nicholas J. Schork,Nicholas J. Schork,Angelo Scuteri,Ayellet V. Segrè,Ayellet V. Segrè,Alan R. Shuldiner,Alan R. Shuldiner,Nicole Soranzo,Nicole Soranzo,Ulla Sovio,Sathanur R. Srinivasan,David P. Strachan,Mar Liis Tammesoo,Emmi Tikkanen,Emmi Tikkanen,Daniela Toniolo,Kim Tsui,Laufey Tryggvadottir,Tyrer Jp,Manuela Uda,Rob M. van Dam,Rob M. van Dam,Joyce B. J. van Meurs,Peter Vollenweider,Gérard Waeber,Nicholas J. Wareham,Dawn M. Waterworth,Michael N. Weedon,H.-Erich Wichmann,Gonneke Willemsen,James F. Wilson,Alan F. Wright,Lauren Young,Guangju Zhai,Wei Vivian Zhuang,Laura J. Bierut,Dorret I. Boomsma,Heather A. Boyd,Laura Crisponi,Ellen W. Demerath,Cornelia M. van Duijn,Michael J. Econs,Tamara B. Harris,David J. Hunter,David J. Hunter,Ruth J. F. Loos,Andres Metspalu,Grant W. Montgomery,Paul M. Ridker,Tim D. Spector,Elizabeth A. Streeten,Kari Stefansson,Kari Stefansson,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,André G. Uitterlinden,Elisabeth Widen,Joanne M. Murabito,Joanne M. Murabito,Ken K. Ong,Ken K. Ong,Anna Murray +196 more
Defining the role of common variation in the genomic and biological architecture of adult human height
Andrew R. Wood,Tõnu Esko,Jian Yang,Sailaja Vedantam,Tune H. Pers,Stefan Gustafsson,Audrey Y. Chu,K. Estrada,Jian'an Luan,Zoltán Kutalik,Najaf Amin,Martin L. Buchkovich,Damien C. Croteau-Chonka,Felix R. Day,Yanan Duan,Tove Fall,Rudolf S N Fehrmann,Teresa Ferreira,Anne U. Jackson,Juha Karjalainen,Ken Sin Lo,Adam E. Locke,Reedik Mägi,Evelin Mihailov,Eleonora Porcu,Joshua C. Randall,André Scherag,Anna A. E. Vinkhuyzen,Harm-Jan Westra,Thomas W. Winkler,Tsegaselassie Workalemahu,Jing Hua Zhao,Devin Absher,Eva Albrecht,Denise Anderson,Jeffrey Baron,Marian Beekman,Ayse Demirkan,Georg Ehret,Bjarke Feenstra,Mary F. Feitosa,Krista Fischer,Ross M. Fraser,Anuj Goel,Jian Gong,Anne E. Justice,Stavroula Kanoni,Marcus E. Kleber,K. Kristiansson,Unhee Lim,Vaneet Lotay,Julian C. Lui,Massimo Mangino,Irene Mateo Leach,Carolina Medina-Gomez,Mike A. Nalls,Dale R. Nyholt,Cameron D. Palmer,Dorota Pasko,Sonali Pechlivanis,Inga Prokopenko,Janina S. Ried,Stephan Ripke,Dmitry Shungin,Alena Stančáková,Rona J. Strawbridge,Yun Ju Sung,Toshiko Tanaka,Alexander Teumer,Stella Trompet,Sander W. van der Laan,Jessica van Setten,Jana V. van Vliet-Ostaptchouk,Zhaoming Wang,Loic Yengo,Weihua Zhang,Uzma Afzal,Johan Ärnlöv,Gillian M. Arscott,Stefania Bandinelli,Amy Barrett,Claire Bellis,Amanda J. Bennett,Christian Berne,Matthias Blüher,Jennifer L. Bolton,Yvonne Böttcher,Heather A. Boyd,Marcel Bruinenberg,Brendan M. Buckley,Steven Buyske,Ida Henriette Caspersen,Peter S. Chines,Robert Clarke,Simone Claudi-Boehm,Mark E. Cooper,E. Warwick Daw,Pim A. de Jong,Joris Deelen,Graciela Delgado,Josh C. Denny,Rosalie A.M. Dhonukshe-Rutten,Maria Dimitriou,Alex S. F. Doney,Marcus Dörr,Niina Eklund,Elodie Eury,Lasse Folkersen,Melissa E. Garcia,Frank Geller,Vilmantas Giedraitis,Alan S. Go,Harald Grallert,Tanja B. Grammer,Jürgen Gräßler,Henrik Grönberg,Lisette C P G M de Groot,C J Groves,Jeffrey Haessler,Per Hall,T. Haller,Göran Hallmans,Anke Hannemann,Catharina A. Hartman,Maija Hassinen,Caroline Hayward,Nancy L. Heard-Costa,Quinta Helmer,Gibran Hemani,Anjali K. Henders,Hans L. Hillege,Mark A. Hlatky,Wolfgang Hoffmann,Per Hoffmann,Oddgeir L. Holmen,Jeanine J. Houwing-Duistermaat,Thomas Illig,Aaron Isaacs,Alan L. James,Janina M. Jeff,Berit Johansen,Åsa Johansson,Jennifer Jolley,Thorhildur Juliusdottir,Juhani Junttila,Abel N. Kho,Leena Kinnunen,Norman Klopp,Thomas Kocher,Wolfgang Kratzer,Peter Lichtner,Lars Lind,Jaana Lindström,Stéphane Lobbens,Mattias Lorentzon,Yingchang Lu,Valeriya Lyssenko,Patrik K. E. Magnusson,Anubha Mahajan,Marc R. Maillard,Wendy L. McArdle,Colin A. McKenzie,Stela McLachlan,Paul J. McLaren,Cristina Menni,Sigrun Merger,Lili Milani,Alireza Moayyeri,Keri L. Monda,M. A. Morken,Gabriele Müller,Martina Müller-Nurasyid,A.W. Musk,Narisu Narisu,Matthias Nauck,Ilja M. Nolte,Markus M. Nöthen,Laticia Oozageer,Stefan Pilz,Nigel W. Rayner,Frida Renström,Neil R. Robertson,Lynda M. Rose,Ronan Roussel,Serena Sanna,Hubert Scharnagl,Salome Scholtens,Fredrick R. Schumacher,Heribert Schunkert,Robert A. Scott,J Sehmi,Thomas Seufferlein,Jianxin Shi,Karri Silventoinen,Johannes H. Smit,Albert V. Smith,Joanna Smolonska,Alice V. Stanton,Kathleen Stirrups,David J. Stott,Heather M. Stringham,Johan Sundström,Morris A. Swertz,Ann-Christine Syvänen,Bamidele O. Tayo,Gudmar Thorleifsson,Jonathan P. Tyrer,Suzanne C. van Dijk,Natasja M. van Schoor,Nathalie van der Velde,Diana van Heemst,Floor V. A. van Oort,S. H. H. M. Vermeulen,Niek Verweij,Judith M. Vonk,Lindsay L. Waite,Melanie Waldenberger,Roman Wennauer,Lynne R. Wilkens,Christina Willenborg,Tom Wilsgaard,Mary K. Wojczynski,Andrew Wong,Alan F. Wright,Qunyuan Zhang,Dominique Arveiler,Stephan J. L. Bakker,John Beilby,Richard N. Bergman,Sven Bergmann,Reiner Biffar,John Blangero,Dorret I. Boomsma,Stefan R. Bornstein,Pascal Bovet,Paolo Brambilla,Morris J. Brown,Harry Campbell,Mark J. Caulfield,Aravinda Chakravarti,Rory Collins,Francis S. Collins,Dana C. Crawford,L. Adrienne Cupples,John Danesh,Ulf de Faire,Hester M. den Ruijter,Raimund Erbel,Jeanette Erdmann,Johan G. Eriksson,Martin Farrall,Ele Ferrannini,Jean Ferrières,Ian Ford,Nita G. Forouhi,Terrence Forrester,Ron T. Gansevoort,Pablo V. Gejman,Christian Gieger,Alain Golay,Omri Gottesman,Vilmundur Gudnason,Ulf Gyllensten,David W. Haas,Alistair S. Hall,Tamara B. Harris,Andrew T. Hattersley,Andrew C. Heath,Christian Hengstenberg,Andrew A. Hicks,Lucia A. Hindorff,Aroon D. Hingorani,Albert Hofman,G. Kees Hovingh,Steve E. Humphries,Steven C. Hunt,Elina Hyppönen,Kevin B. Jacobs,Marjo-Riitta Järvelin,Pekka Jousilahti,Antti Jula,Jaakko Kaprio,John J. P. Kastelein,Manfred Kayser,Frank Kee,Keinänen-Kiukaanniemi S,Lambertus A. Kiemeney,Jaspal S. Kooner,Charles Kooperberg,Seppo Koskinen,Peter Kovacs,Aldi T. Kraja,Meena Kumari,Johanna Kuusisto,Timo A. Lakka,Claudia Langenberg,Loic Le Marchand,Terho Lehtimäki,Sara Lupoli,Pamela A. F. Madden,Satu Männistö,Paolo Manunta,Andre Marette,Tara C. Matise,Barbara McKnight,Thomas Meitinger,Frans L. Moll,Grant W. Montgomery,Andrew D. Morris,Andrew P. Morris,Jeffrey C. Murray,Mari Nelis,Claes Ohlsson,Albertine J. Oldehinkel,Ken K. Ong,Willem H. Ouwehand,Gerard Pasterkamp,Annette Peters,Peter P. Pramstaller,Jackie F. Price,Lu Qi,Olli T. Raitakari,Tuomo Rankinen,Dabeeru C. Rao,Treva Rice,Marylyn D. Ritchie,Igor Rudan,Veikko Salomaa,Nilesh J. Samani,Jouko Saramies,Mark A. Sarzynski,Peter E. H. Schwarz,Sylvain Sebert,Peter S. Sever,Alan R. Shuldiner,Juha Sinisalo,Valgerdur Steinthorsdottir,Ronald P. Stolk,Jean-Claude Tardif,A Tönjes,Angelo Tremblay,Elena Tremoli,Jarmo Virtamo,Marie-Claude Vohl,Philippe Amouyel,Folkert W. Asselbergs,Themistocles L. Assimes,Murielle Bochud,Bernhard O. Boehm,Eric Boerwinkle,Erwin P. Bottinger,Claude Bouchard,Stéphane Cauchi,John C. Chambers,Stephen J. Chanock,Richard S. Cooper,Paul I.W. de Bakker,George Dedoussis,Luigi Ferrucci,Paul W. Franks,Philippe Froguel,Leif Groop,Christopher A. Haiman,Anders Hamsten,M. Geoffrey Hayes,Jennie Hui,David J. Hunter,Kristian Hveem,J. Wouter Jukema,Robert C. Kaplan,Mika Kivimäki,Diana Kuh,Markku Laakso,Yongmei Liu,Nicholas G. Martin,Winfried März,Mads Melbye,Susanne Moebus,Patricia B. Munroe,Inger Njølstad,Ben A. Oostra,Colin N. A. Palmer,Nancy L. Pedersen,Markus Perola,Louis Pérusse,Ulrike Peters,Joseph E. Powell,Chris Power,Thomas Quertermous,Rainer Rauramaa,Eva Reinmaa,Paul M. Ridker,Fernando Rivadeneira,Jerome I. Rotter,T. Saaristo,Danish Saleheen,David Schlessinger,P. Eline Slagboom,Harold Snieder,Tim D. Spector,Konstantin Strauch,Michael Stumvoll,Jaakko Tuomilehto,Matti Uusitupa,Pim van der Harst,Henry Völzke,Mark Walker,Nicholas J. Wareham,Hugh Watkins,H.-Erich Wichmann,James F. Wilson,Pieter Zanen,Panos Deloukas,Iris M. Heid,Cecilia M. Lindgren,Karen L. Mohlke,Elizabeth K. Speliotes,Unnur Thorsteinsdottir,Inês Barroso,Caroline S. Fox,Kari E. North,David P. Strachan,Jacques S. Beckmann,Sonja I. Berndt,Michael Boehnke,Ingrid B. Borecki,Mark I. McCarthy,Andres Metspalu,Kari Stefansson,André G. Uitterlinden,Cornelia M. van Duijn,Lude Franke,Cristen J. Willer,Alkes L. Price,Guillaume Lettre,Ruth J. F. Loos,Michael N. Weedon,Erik Ingelsson,Jeffrey R. O'Connell,Gonçalo R. Abecasis,Daniel I. Chasman,Michael E. Goddard,Peter M. Visscher,Joel N. Hirschhorn,Timothy M. Frayling +444 more