12 research outputs found
Computational imaging and automated identification for aqueous environments
- Publication venue
- Massachusetts Institute of Technology
- Publication date
- 01/01/2011
- Field of study
Thesis (Ph. D.)--Joint Program in Oceanography/Applied Ocean Science and Engineering (Massachusetts Institute of Technology, Dept. of Mechanical Engineering; and the Woods Hole Oceanographic Institution), 2011."June 2011." Cataloged from PDF version of thesis.Includes bibliographical references (p. 253-293).Sampling the vast volumes of the ocean requires tools capable of observing from a distance while retaining detail necessary for biology and ecology, ideal for optical methods. Algorithms that work with existing SeaBED AUV imagery are developed, including habitat classification with bag-of-words models and multi-stage boosting for rock sh detection. Methods for extracting images of sh from videos of long-line operations are demonstrated. A prototype digital holographic imaging device is designed and tested for quantitative in situ microscale imaging. Theory to support the device is developed, including particle noise and the effects of motion. A Wigner-domain model provides optimal settings and optical limits for spherical and planar holographic references. Algorithms to extract the information from real-world digital holograms are created. Focus metrics are discussed, including a novel focus detector using local Zernike moments. Two methods for estimating lateral positions of objects in holograms without reconstruction are presented by extending a summation kernel to spherical references and using a local frequency signature from a Riesz transform. A new metric for quickly estimating object depths without reconstruction is proposed and tested. An example application, quantifying oil droplet size distributions in an underwater plume, demonstrates the efficacy of the prototype and algorithms.by Nicholas C. Loomis.Ph.D
Формирование эмоциональной культуры как компонента инновационной культуры студентов
- Author
- A Abdellaoui
- A Garrod
- A Wright
- Abdel Abdellaoui
- Adesola Ogunniyi
- Adolfo Correa
- Alan F. Wright
- Alan R. Shuldiner
- Alanna Morrison
- Albert V. Smith
- Albertine J. Oldehinkel
- Alena Stančáková
- Alexander Drong
- Alexander Teumer
- Alice V. Stanton
- Aliki-Eleni Farmaki
- Amelie Bonnefond
- Anders Hamsten
- Andre G. Uitterlinden
- Andres Metspalu
- Andrew A. Hicks
- Andrew Bjonnes
- Andrew D. Morris
- Andrew P. Morris
- Andrew R. Wood
- Angela Matchan
- Anil K. Giri
- Anke Tönjes
- Anna Maria Töglhofer
- Annamari Lundqvist
- Anne U. Jackson
- Anni Joensuu
- Antonietta Robino
- Antti-Pekka Sarin
- Anu Loukola
- AR Wood
- Aravinda Chakravarti
- Archie Campbell
- Ashley van der Spek
- Astrid van Hylckama Vlieg
- Atsushi Takahashi
- Babatunde Salako
- Bamidele O. Tayo
- Bengt Sennblad
- Benjamin Lehne
- Beverley Balkau
- Bjarke Feenstra
- Blair H. Smith
- Bruce M. Psaty
- C Darwin
- C Darwin
- CA Rietveld
- Carole Ober
- Caroline Hayward
- Caroline S. Fox
- Cecilia M. Lindgren
- Charles Gu
- Charles N. Rotimi
- Chittaranjan S. Yajnik
- Chris Haley
- Christa Meisinger
- Christian Gieger
- Christopher J. Hammond
- Cinzia Sala
- CJ Willer
- Claude Bouchard
- Claudia Schurmann
- Clemens Baumbach
- Colin N. A. Palmer
- Constance Chen
- Cornelia M. van Duijn
- Cornelius A. Rietveld
- Corrado Masciullo
- Cristian Pattaro
- Cristina Menni
- D Charlesworth
- Daniel I. Chasman
- Daniel J. Benjamin
- Daniel Shriner
- Daniela Ruggiero
- Daniela Toniolo
- Daniele Cusi
- David A. Mackey
- David C.M. Liewald
- David J. Porteous
- David P. Strachan
- David R. Weir
- Degui Zhi
- Dhananjay Vaidya
- Dharambir K. Sanghera
- Diane M. Becker
- Diego Vozzi
- Donna K. Arnett
- Dorret I. Boomsma
- Dragana Vuckovic
- Dwaipayan Bharadwaj
- Edith Hofer
- Eero Vuoksimaa
- Efthymia Vlachopoulou
- Eleftheria Zeggini
- Eric Boerwinkle
- Erik Ingelsson
- Erika Salvi
- Erin B. Ware
- Erkki Vartiainen
- Erwin P. Bottinger
- Evelin Mihailov
- F Galton
- Folkert W. Asselbergs
- Francesca Pavani
- Francine Grodstein
- Francis S. Collins
- Frank D. Mentch
- Frank Geller
- Gail Davies
- GB Ehret
- Generation Scotland
- Georg Ehret
- Georg Homuth
- George Davey Smith
- George Dedoussis
- George T. O'Connor
- Gerard Pasterkamp
- Gianluigi Zaza
- Gibran Hemani
- Giorgia Girotto
- Giovanni Gambaro
- Giovanni Malerba
- Giriraj R. Chandak
- Gonneke Willemsen
- Grant W. Montgomery
- H Campbell
- H Lango Allen
- H Najmabadi
- H Stefansson
- Hakon Hakonarson
- Hannele Mattsson
- Hans Bisgaard
- Hao Mei
- Harri Rissanen
- Harry Campbell
- Heikki A. Koistinen
- Helen R. Warren
- Helena Schmidt
- Henning Tiemeier
- Hugoline G. de Haan
- I Rudan
- Ian Ford
- Ian J. Deary
- Igor Rudan
- IJ Deary
- Ilaria Gandin
- Ilja Demuth
- Ilja M. Nolte
- Inga Patarcic
- Inga Prokopenko
- Ingrid B. Borecki
- Irina Gillham-Nasenya
- J Gibson
- J. Wouter Jukema
- Jaakko Kaprio
- Jaakko Tuomilehto
- James B. Meigs
- James F. Wilson
- James G. Wilson
- James S. Pankow
- Jari Lahti
- Jaspal S. Kooner
- JE Powell
- Jeffrey R. O'Connel
- Jennifer A. Smith
- Jennifer E. Huffman
- Jerome I. Rotter
- Jessica D. Faul
- Jessica van Setten
- JI Hoffman
- Jie Yao
- Jing Hua Zhao
- Jinyan Huang
- Joel N. Hirschhorn
- Johan G. Eriksson
- Johanna Kuusisto
- John B. Whitfield
- John C. Chambers
- John Connell
- John M. Starr
- John R. B. Perry
- Jonathan P. Bradfield
- Josée Dupuis
- Jouke-Jan Hottenga
- JR Flynn
- Juha Sinisalo
- JV Neel
- Karen L. Mohlke
- Kari E. North
- Kauko Heikkilä
- Kent D. Taylor
- Kirsi Pietilainen
- Koichi Matsuda
- Konstantin Strauch
- KW Broman
- L Ronnegard
- L. Adrienne Cupples
- LA Weiss
- Lars Bertram
- Lars Lind
- Laura J. Scott
- Lawrence F. Bielak
- Lazaros Lataniotis
- Leanne M. Hall
- Lenore J. Launer
- Lihua Wang
- Lili Milani
- Lisa R. Yanek
- Lisbeth Carstensen
- Loic Yengo
- Lorraine Southam
- Louis Pérusse
- Luigi Ferrucci
- LV Hedges
- Lyn R. Griffiths
- Lynda M. Rose
- Lynne J. Hocking
- M Kirin
- M Soler Artigas
- M. Arfan Ikram
- MA Nalls
- Maciej Tomaszewski
- Mads Melbye
- Magnus Johannesson
- Manraj K. Kooner
- Marcus Dörr
- Margie J. Wright
- Mari Nelis
- Maria G. Stathopoulou
- Maria Pina Concas
- Marie Loh
- Marilyn C. Cornelis
- Marina Ciullo
- Mario Pirastu
- Marja-Liisa Lokki
- Mark Abney
- Mark J. Caulfield
- Markku Laakso
- Markku S. Nieminen
- Markus Perola
- Mary F. Feitosa
- Massimo Mangino
- Matthew A. Allison
- Matthew J. Suderman
- May E. Montasser
- MC Keller
- MC Keller
- Melanie Waldenberger
- Michael Boehnke
- Michela Traglia
- Michiaki Kubo
- Mika Kähönen
- Miles C. Benton
- Misa Graff
- Najaf Amin
- Nancy L. Heard-Costa
- Natalia Tšernikova
- Naveed Sattar
- Nazir M. Khan
- NE Morton
- Neil Poulter
- Nele Friedrich
- Nicholas D. Hastie
- Nicholas G. Martin
- Nicholas J. Timpson
- Nicholas J. Wareham
- Nicola Pirastu
- Nicole Soranzo
- Niek Verweij
- Niina Eklund
- Nikhil Tandon
- Nilesh J. Samani
- Nona Sotoodehnia
- Nora Franceschini
- Olga McLeod
- Olli Raitakari
- Omri Gottesman
- Ozren Polašek
- Panos Deloukas
- Paolo Gasparini
- Patricia A. Peyser
- Patricia B. Munroe
- Patrik K. E. Magnusson
- Pau Navarro
- Paul Knekt
- Paul M. Ridker
- Paul Redmond
- Pedro Marques-Vidal
- Pekka Jousilahti
- Penelope A. Lind
- Peter J. van der Most
- Peter K. Joshi
- Peter Kraft
- Peter Sever
- Peter Vollenweider
- Philipp Koellinger
- Philippe Froguel
- Pim van der Harst
- Pirro G. Hysi
- R McQuillan
- R McQuillan
- R. Graham Barr
- RA Scott
- Rajiv Nadukuru
- Rany M. Salem
- Rasika A. Mathias
- RE Marioni
- RE Marioni
- Reedik Mägi
- Reinhold Schmidt
- Richa Saxena
- Richard H. Myers
- Richard Rose
- Richard S. Cooper
- Robert A. Scott
- Rodney A. Lea
- Rona J. Strawbridge
- Ruth J. F. Loos
- S Purcell
- S Wright
- S Wright
- Sailaja Vedantam
- Saira S. Mirza
- Sander W. van der Laan
- Sandosh Padmanabhan
- Sarah E. Harris
- Sarah E. Medland
- Sarah Wild
- Sarju Ralhan
- Satu Männistö
- Sebastian E. Baumeister
- Seyhan Yazar
- Sharon L. R. Kardia
- Sheila Ulivi
- Shona M. Kerr
- Sian-Tsun Tang
- Smeeta Shrestha
- Sonja I. Berndt
- Stavroula Kanoni
- Stefan Enroth
- Stefania Cappellani
- Stella Trompet
- Stephan J. L. Bakker
- Stephanie J. London
- Stephanie J. Loomis
- Stephen B. Ellis
- Stephen J. Chanock
- Stephen S. Rich
- Steven C. Hunt
- Struan F.A. Grant
- Sudha Seshadri
- Suraj S. Nongmaithem
- Sven Bergmann
- Tamara B. Harris
- Tanguy Corre
- Tarunveer S. Ahluwalia
- Teresa Nutile
- Terho Lehtimäki
- Thomas Lumley
- Thomas Meitinger
- Thorkild I. A. Sørensen
- Tian Liu
- Tim D. Spector
- Tim Kacprowski
- Timothy M. Frayling
- TJ Pemberton
- Tonu Esko
- Traci M. Bartz
- Tugce Karaderi
- Tuula Vasankari
- Ulf Gyllensten
- Ulman Lindenberger
- Ulrich Broeckel
- Uzma Afzal
- Veikko Salomaa
- Veronique Vitart
- Vilmundur Gudnason
- Walter R. Palmas
- Wei Zhao
- Weihua Meng
- Weihua Zhang
- William R. Scott
- William Wentworth-Shields
- Xiaofeng Zhu
- Xiuqing Guo
- Y.-D. Ida Chen
- Ying Wu
- Yingchang Lu
- Yingleong Chan
- Yoichiro Kamatani
- YS Aulchenko
- YS Aulchenko
- Yukinori Okada
- Yuning Chen
- Zhaoming Wang
- Åsa Johansson
- Publication venue
- Российский государственный профессионально-педагогический университет
- Publication date
- 01/01/2009
- Field of study
Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
- Author
- Aaltonen M
- Abdur Rahman M
- Abell T
- Abide W. Jr
- Acheatel R
- Achiri P
- Acon J
- Adams T
- Affinito S
- Agarwal S
- Aggarwal K
- Aggarwal R
- Ahlström P
- Ahmad A
- Ahmed M
- Aillon C
- Airaksinen A
- Ait-sadi R
- Akers J
- Al-jumaily J
- Albers C
- Albert M
- Alberti A
- Alexander T
- Alford C
- Algotsson L
- Allen T
- Allworth M
- Almond E
- Aloisi A
- Alternburg C
- Alton M
- Amin J
- Amundson A
- Andersen K
- Andersen M
- Anderson E
- Anderson G
- Anderson R
- Anderson T
- Andersson H
- Andersson L
- Andreo J
- Andres C
- Andresen D
- Andrews G
- Andrews L
- Andrews R
- Andrioli V
- Angermann Ce
- Annas T
- Ansell V
- Antonio-drabek C
- Antonishen D
- Antonishen M
- Anuschek V
- Appel Kf
- Appel S
- Appleyard D
- Archer A
- Armitage J
- Armstrong L
- Armstrong M
- Arnesson K
- Arnold M
- Arora P
- Arp H
- Asbill B
- Ashbrook-raby C
- Ashton L
- Assarsson E
- Audet K
- Augenbraun C
- Aung HNIN THANDA
- Auscher S
- Ausner J
- Aviles R
- Awasty V
- Axelsson U
- Ayers S
- Ayub H
- Babar G
- Babington G
- Backlund M
- Badal B
- Baggiore C
- Baghiana S
- Bai H
- Bai J
- Baigent C
- Baillargeon G
- Bakbak A
- Baker S
- Baldin Mg
- Baldini E
- Baldwin E
- Ballantyne C
- Baltic A
- Banerjee S
- Bang Hansen M
- Banks K
- Bansilal S
- Barkley-daughtry S
- Barnes D
- Barnes E
- Barnett S
- Baroni Claudio
- Barry S
- Barter P
- Bartolomei Mecatti B
- Barton I
- Barton J
- Baré C
- Bashton D
- Basler M
- Bastani L
- Basvi P
- Batchlett K
- Bateman S
- Battistelli E
- Baty J
- Bauersachs J
- Bauman A
- Bavendiek U
- Baxter A
- Bayly G
- Bays H
- Beasley T
- Beck P
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- Been M
- Begg R
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- Beilker J
- Beißner S
- Bekfani T
- Belanger B
- Belew K
- Bellaby J
- Bellamy C
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- Beneat Am
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- Benoni S
- Bentivenga L
- Benton R
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- Berge C
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- Bernardinangeli M
- Bernstein R
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- Spencer R
- Sprafka L
- Sprechert D
- Sprenger C
- Springer K
- Springer W
- Srivastava S
- St-amour E
- Stadler A
- Stadsnes S
- Stafford C
- Stage Jensen B
- Standring R
- Staniloae C
- Stastny C
- Stata C
- Stawecki L
- Stearn S
- STEELE-DAVIES KAMALA DEVI
- Steen D
- Stefanin C
- Steinberg M
- Steingard S
- Stellbrink C
- Stellbrink E
- Stender S
- Stephens J
- Stevens W
- Stewart WILLIAM CHARLES
- Stich M
- Stiehl S
- Stinson J
- Stjernberg M
- Stobbe O
- Stock R
- Stockport J
- Stodle R
- Stoeckicht Y
- Stolz R
- Stolze K
- Storey B
- Storgaard M
- Stover T
- Stowe F
- Strader J. Jr
- Strandberg M
- Strandberg T
- Stratz C
- Streuber-bouhksas T
- Strubberg K
- Strupp G
- Strömer H
- Stuart A
- Stuckey T
- Styllou P
- Su H
- Su S
- Su W
- Su X
- Suarez M
- Sullivan S
- Summerhayes A
- Sun Chengjie
- Sun G
- Sun Hengyu
- Sun L
- Sun S
- Sun Y
- Sun Z
- Sundholm C
- Suttling A
- Sutton J
- Sutton M
- Sutton R
- Svenningsen A
- Svensson Ka
- Svingen G
- Svingen S
- Swailes L
- Swan J
- Sydow K
- Syed S
- Sykulski R
- Szacinski G
- Szalanski N
- Szczesnak S
- Søndergaard S
- Sørensen G
- Sørensen V
- Sülflow S
- Tabandeh A
- Taheri H
- Tahir N
- Tahirkheli N
- Tajouaout K
- Talano J
- Tami L
- Tanaka A
- Taneja A
- Tang R
- Tang X
- Tanggaard L
- Tanney C
- Tanqueray E
- Tarnow L
- Tarquini B
- Tarras Wahlberg M
- Taurio J
- Tawara K
- Taylor Bennett A
- Taylor D
- Taylor J
- Taylor K
- Taylor P
- Techmanski M
- Tedder B
- Teige M
- Teklinski A
- Temporelli B
- Teramoto T
- Testa P
- Tevik Bjøru H
- Thakkar M
- Thalamus J
- Thevakumaran Y
- Thieme R
- Thomas CHERYL ANNE
- Thompson N
- Thomsen K
- Thorington S
- Thorne H
- Thorsby I
- Thorsen J
- Thott O
- Thulin J
- Thunhaug H
- Tigges E
- Tilseth R
- Tilton N
- Tilvis R
- Timadjer A
- Timberg I
- Tischner G
- Tisthammer Antonsen H
- Tobert J
- Tobiansky J
- Todd H
- Tofstad C
- Toghill V
- Tomassini L
- Tomita A
- Tompkins J
- Tomson J
- Tong L
- Tong Q
- Tonkin A
- Tonks L
- Torp Pedersen C
- Torre B
- Torres E
- Torstensson I
- Traboulssi M
- Trahan J
- Tran A
- Travill C
- Treasure C
- Treasure L
- Tremblay C
- Tremblay I
- Trenk D
- Trepels T
- Trevelyan J
- Trevithick C
- Trippel T
- Troy J
- Truthan K
- Tscholl V
- Tu E
- Tummos E
- Tuominen Ml
- Turkerud Söby E
- Turner C
- Tuseth N
- Twelker K
- Tyler D
- Tyler J
- Törnqvist Å
- Udsen G
- Uggeldahl I
- Ukkola L
- Ukkola O
- Ul Haq I
- Urbani C
- Urso L
- Uslar S
- Utech A
- Uusitalo S
- Vadmann H
- Vaine T
- Valdes-marquez E
- Valpas S
- Valtonen M
- Van Leijenhorst G
- Vandenberg K
- Varakas M
- Vargas B
- Varma S
- Vasko P
- Vassbotten I
- Vaughn J
- Vavik V
- Vaz S
- Veerina K
- Velky J
- Veng-olsen T
- Vester S
- Vestre M
- Vicari Ruben
- Vickers C
- Viera Moreno J
- Vingsnes T
- Vinter K
- Viswanath D
- Vivaldi F
- Vizel S
- Vlaheli D
- Voehringer H
- Voehringer M
- Voelkers M
- Vogel CHIARA EUGENIA
- Voigt S
- Von Jessen G
- Vuola M
- Völler H
- Waetzold K
- Wagoner S
- Wahl W
- Wain J
- Waldie H
- Walker E
- Walker MANUEL DAVID
- Wallendszus K
- Waltenberger J
- Walton A
- Walton E
- Wan Z
- Wang Chengqiang
- Wang Dajian
- Wang F
- Wang FLORIAN LIFAN
- Wang G
- Wang H
- Wang J
- Wang PENG FEI
- Wang Qi
- Wang R
- Wang Shiyang
- Wang W
- Wang X
- Wang Yuning
- Wang Z
- Wanner C
- Warke L
- Warren K
- Washington K
- Waters A
- Waters E
- Watkins B
- Watkins H
- Watson S
- Watts M
- Weaving L
- Weber T
- Webster J
- Wei Xichun
- Weiderman A
- Weidmann B
- Weigt D
- Weil J
- Weisberger J
- Weise I
- Weiss N
- Weiss R
- Weiter K
- WELTIN-WU Colin
- Wenzel I
- Wenzelburger I
- Werenskjold E
- Werner N
- Werner S
- Werth S
- West A
- West C
- West K
- Westerheim E
- Weston C
- Westphal S
- Wheatley K
- Wheeler J
- Wheeler S
- Whisnant T
- Whitney K
- Wiberg S
- Wickman M
- Wiechert C
- Wiggers H
- Wiik S
- Wiik-karu S
- Wikström P
- Wilberg Rebnord E
- Wilcox H
- Wilcox L
- Wilke K
- Willett M
- Willetts S
- Williams L
- Williams P
- Williams T
- Williamson C
- Wilsch R
- Wilson A
- Wilson E
- Wilson P
- Wincott E
- Winey-ward D
- Winstead J
- Wintour J
- Wiseman D
- Wiviott Sd
- Wodlin P
- Womack L
- Wong Y
- Wood D
- Woodford C
- Woods J
- Wotorson L
- Wright L
- Wu G
- Wu R
- Wu S
- Wu W
- Wu X
- Wu Zhe
- Wynne S
- Wölfl C
- Xia J
- Xiao L
- Xiao R
- Xie M
- Xie R
- Xing C
- Xing W
- Xiong J
- Xu B
- Xu DAN YI
- Xu J
- Xu T
- Yan H
- Yan Xiaoting
- Yandamuri S
- Yang HEE JUNG
- Yang HEE JUNG
- Yang M
- Yang P
- Yang Q
- Yang T
- Yang X
- Yang Y
- Yang Z
- Yao H
- Yao X
- Yao Y
- Yao Z
- Yashinski C
- Ye G
- Yedinak S
- Yeh N
- Yeung M
- Young A
- Young C
- Young L
- Yu B
- Yu H
- Yu Q
- Yuan Y
- Yunes R
- Zadra R
- Zagnoni S
- Zambelli M
- Zbik S
- Zebrack J
- Zelenka J
- Zelik J
- Zeuthen E
- Zhai M
- Zhang A
- Zhang B
- Zhang C
- Zhang F
- Zhang H
- Zhang J
- Zhang L
- Zhang R
- Zhang S
- Zhang Ting
- Zhang Wen
- Zhang X
- Zhang Y
- Zhao C
- Zhao JIAYI STELLA
- Zhao L
- Zhao P
- Zhao R
- Zhao Y
- Zheng Y
- Zheng Z
- Zhi Y
- Zhong H
- Zhong R
- Zhou C
- Zhou Juan
- Zhou Xingyu
- Zhou Yingyuan
- Zhu Wangqin
- Zhu X
- Zhu Y
- Ziefle S
- Zilz N
- Zineldine A
- Zlatewa R
- Zoghbi J
- Zong C
- Zong D
- Zong X
- Zuchelkowski A
- Zulauf N
- Ågårdh A
- Öner A
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2017
- Field of study
BACKGROUND:
Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.
METHODS:
We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.
RESULTS:
During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.
CONCLUSIONS:
Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)
Recommended from our members
Associations of autozygosity with a broad range of human phenotypes
- Author
- Adeyemo Adebowale A
- Afaq Saima
- Aguilar-Salinas Carlos Alberto
- Akiyama Masato
- Albert Matthew L
- Allison Matthew A
- Alver Maris
- Amin Najaf
- Asselbergs Folkert W
- Aung Tin
- Azizi Fereidoun
- Bakker Stephan J L
- Bao Yanchun
- Barnes Catriona L K
- Bartz Traci M
- Baumbach Clemens
- Becker Diane M
- Bennett David A
- Bentley Amy R
- Berndt Sonja I
- Bharadwaj Dwaipayan
- Bielak Lawrence F
- Biino Ginevra
- Bixley Matthew J
- Bochud Murielle
- Boehnke Mike
- Boeing Heiner
- Boerwinkle Eric
- Borja Judith B
- Bottinger Erwin P
- Bouchard Claude
- Bradfield Jonathan P
- Brody Jennifer A
- Broer Linda
- Brumat Marco
- Campbell Archie
- Campbell Harry
- Carmi Shai
- Caulfield Mark J
- Cesarini David
- Chai Jin-Fang
- Chambers John C
- Chandak Giriraj Ratan
- Chanock Stephen
- Chasman Daniel I
- Chee Miao-Li
- Chen Guanjie
- Chen Yii-Der I
- Chen Zhengming
- Cheng Ching-Yu
- Chiu Yen-Feng
- Ciullo Marina
- Clark David W
- Cocca Massimiliano
- Collins Francis S
- Concas Maria Pina
- Corley Janie
- Cornelis Marilyn
- Corre Tanguy
- Cousminer Diana L
- Cugliari Giovanni
- Cusi Daniele
- Damulina Anna
- Daneshpour Maryam S
- Day Felix R
- de Borst Gert J
- de Haan Hugoline G
- De Jager Philip L
- de Kleijn Dominique P V
- de Mutsert Renée
- Deary Ian J
- Deelen Patrick
- Dekker Annelot M
- Delgado Graciela E
- Den Ruijter Hester M
- Dhana Klodian
- Doney Alexander S F
- Dorajoo Rajkumar
- Doumatey Ayo P
- Dzimiri Nduna
- Dörr Marcus
- Ebenesersdóttir S Sunna
- Eccles David A
- Ellinghaus David
- Elliott Joshua
- Elliott Paul
- Erdmann Jeanette
- Eriksson Johan G
- Esko Tōnu
- Evangelou Evangelos
- Evans Michele K
- Ewert Ralf
- Faul Jessica D
- Feenstra Bjarke
- Feitosa Mary
- Felix Janine F
- Fischer Krista
- Foisy Sylvain
- Franceschini Nora
- Franke Andre
- Franke Lude
- Freedman Barry I
- Friedlander Yechiel
- Fuchsberger Christian
- Gandin Ilaria
- Gao He
- Gasparini Paolo
- Germain Marine
- Gieger Christian
- Girotto Giorgia
- Giulianini Franco
- Goel Anuj
- Gonzalez Clicerio
- Goodarzi Mark O
- Gordon Scott D
- Goyette Philippe
- Graff Mariaelisa
- Granot-Hershkovitz Einat
- Grant Struan F A
- Griffiths Lyn R
- Grodstein Francine
- Groop Leif
- Guarrera Simonetta
- Gudbjartsson Daniel F
- Gudnason Vilmundur
- Guity Kamran
- Gunnarsson Bjarni
- Guo Xiuqing
- Guo Yu
- Gyllensten Ulf
- Gögele Martin
- Hagenaars Saskia P
- Haiman Christopher A
- Hakonarson Hakon
- Halevy Avner
- Haley Chris S
- Hamsten Anders
- Harris Sarah E
- Harris Tamara B
- Hayward Caroline
- Hedayati Mehdi
- Helgason Agnar
- Heng Chew-Kiat
- Hicks Andrew A
- Hirata Makoto
- Hochner Hagit
- Hofer Edith
- Hsiung Chao Agnes
- Huang Jinyan
- Huerta-Chagoya Alicia
- Huikuri Heikki
- Hung Yi-Jen
- Hunt Steven C
- Höfer Imo
- Igartua Catherine
- Ikram M Arfan
- Jaddoe Vincent W V
- Jagadeesan Anuradha
- Jansen Iris E
- Jia Yucheng
- Johannesson Magnus
- Johansson Åsa
- Jonas Jost B
- Joshi Peter K
- Jousilahti Pekka
- Jukema J Wouter
- Junttila Juhani
- Kacprowski Tim
- Kamatani Yoichiro
- Kanai Masahiro
- Kaprio Jaakko
- Kardia Sharon L. R.
- Karlsson Robert
- Karlsson Torgny
- Karpe Fredrik
- Kerrison Nicola D
- Kessler Thorsten
- Khaw Kay-Tee
- Khor Chiea Chuen
- Kleber Marcus E
- Koh Woon-Puay
- Kolcic Ivana
- Kooner Jaspal S
- Kraft Peter
- Krämer Bernhard K
- Kubo Michiaki
- Kumari Meena
- Kutalik Zoltán
- Kuusisto Johanna
- Laakso Markku
- Lahti Jari
- Langenberg Claudia
- Laudes Matthias
- Launer Lenore J
- Lawlor Deborah A
- Lea Rodney A
- Lee I-Te
- Lee Wen-Jane
- Lehne Benjamin
- Lerch Markus M
- Li Liming
- Li Shengchao Alfred
- Li-Gao Ruifang
- Lieb Wolfgang
- Lin Kuang
- Liu Jianjun
- Loh Marie
- London Stephanie J
- Loomis Stephanie
- Loos Ruth J. F.
- Lu Yingchang
- Luan Jian’an
- Lumley Thomas
- Magnusson Patrik K. E.
- Mahajan Anubha
- Manichaikul Ani W
- Manunta Paolo
- Martin Nicholas G
- Mason Dan
- Matoba Nana
- Matsuda Koichi
- Mattsson Hannele
- Matullo Giuseppe
- McCarthy Mark I
- Medina-Gomez Carolina
- Medland Sarah E
- Mei Xue W
- Meidtner Karina
- Meisinger Christa
- Meitinger Thomas
- Meng Weihua
- Merriman Tony R
- Metspalu Andres
- Meyer Brian F
- Mezzavilla Massimo
- Milani Lili
- Millwood Iona Y
- Mohlke Karen L
- Momozawa Yukihide
- Montasser May E
- Montgomery Grant W
- Mook-Kanamori Dennis
- Moore Amy
- Moore Kristjan H S
- Morange Pierre-Emmanuel
- Moreno-Macías Hortensia
- Mori Trevor A
- Morrison Alanna C
- Muka Taulant
- Munroe Patricia B
- Munz Matthias
- Murakami Yoshinori
- Murray Alison D
- Mychaleckyj Josyf C
- Másson Gísli
- Mägi Reedik
- März Winfried
- Nalls Mike A
- Nauck Matthias
- Neville Matt J
- Nolte Ilja M
- North Kari E
- Nutile Teresa
- Nyholt Dale R
- Ober Carole
- Okada Yukinori
- Oldehinkel Albertine J
- Ong Ken K
- Orozco Lorena
- O’connell Jeffery R
- Padmanabhan Sandosh
- Palmas Walter
- Palmer Colin
- Palviainen Teemu
- Pankow James S
- Pasterkamp Gerard G
- Patin Etienne
- Pattaro Cristian
- Pattie Alison
- Pennell Craig E
- Perola Markus
- Perry John R. B.
- Perusse Louis
- Peyser Patricia A
- Pirastu Mario
- Pirastu Nicola
- Polasek Ozren
- Polderman Tinca J. C.
- Porteous David J
- Posthuma Danielle
- Poulter Neil
- Pramstaller Peter P
- Prasad Gauri
- Prasad Rashmi B
- Priyanka Tallapragada Divya Sri
- Psaty Bruce M
- Pálsson Gunnar
- Quintana-Murci Lluis
- Ralhan Sarju
- Rao Dabeeru C
- Rich Stephen S
- Ridker Paul M
- Rietveld Cornelius A
- Rioux John D
- Rivadeneira Fernando
- Rizzi Federica
- Robino Antonietta
- Rohde Rebecca
- Rotimi Charles
- Rotter Jerome I
- Rudan Igor
- Ruggiero Daniela
- Räikkönen Katri
- Saba Yasaman
- Sabanayagam Charumathi
- Sabater-Lleal Maria
- Sala Cinzia Felicita
- Salomaa Veikko
- Salvi Erika
- Sandow Kevin
- Sanghera Dharambir K
- Sapkota Bishwa R
- Sattar Naveed
- Schmidt Helena
- Schmidt Reinhold
- Schulze Matthias B
- Schunkert Heribert
- Schurmann Claudia
- Scott Laura J
- Scott Robert A
- Scott William R
- Sedaghati-Khayat Bahareh
- Sennblad Bengt
- Sever Peter J
- Sheu Wayne H-H
- Shi Yuan
- Shrestha Smeeta
- Shriner Daniel
- Shukla Sharvari Rahul
- Shuldiner Alan R
- Sigurdsson Jon K
- Sikka Timo Tonis
- Sim Xueling
- Singh Jai Rup
- Skotte Line
- Small Neil
- Smart Melissa C
- Smith Albert Vernon
- Smith Blair H
- Smith George Davey
- Smith Jennifer A
- Sotoodehnia Nona
- Spracklen Cassandra N
- Stanton Alice
- Stančáková Alena
- Starr John M
- Stefansdottir Lilja
- Stefansson Kari
- Straker Leon
- Strawbridge Rona J
- Sulem Patrick
- Sveinbjornsson Gardar
- Swertz Morris A
- Tai E-Shyong
- Tajuddin Salman M
- Taylor Adele M
- Taylor Kent D
- Terzikhan Natalie
- Teumer Alexander
- Tham Yih-Chung
- Thorleifsson Gudmar
- Thorsteinsdottir Unnur
- Tillander Annika
- Timpson Nicholas J
- Toniolo Daniela
- Tracy Russell P
- Tregouet David-Alexandre
- Trompet Stella
- Tuomi Tiinamaija
- Turman Constance
- Tusié-Luna Teresa
- Tzoulaki Ioanna
- Uitterlinden André G
- Vaccargiu Simona
- van Dam Rob M
- van den Berg Leonard H
- van der Harst Pim
- van der Laan Sander W
- van der Most Peter J
- van der Spek Ashley
- van Duijn Cornelia M
- van Eijk Kristel R
- van Heel David A
- van Rheenen Wouter
- van Rooij Frank J A
- van Setten Jessica
- Vangipurapu Jagadish
- Veldink Jan H
- Verweij Niek
- Viberti Clara
- Vitart Veronique
- Vollenweider Peter
- Vuoksimaa Eero
- Völker Uwe
- Wakil Salma M
- Waldenberger Melanie
- Walters Robin G
- Wander Gurpreet S
- Wang Carol A
- Wang Lihua
- Wang Ya Xing
- Wareham Nicholas J
- Warren Helen R
- Weir David R
- Whitfield John B
- Wijmenga Cisca
- Wild Sarah
- Wilson James F
- Wong Tien-Yin
- Wootton Robyn E
- Wright John
- Yajnik Chittaranjan S
- Yanek Lisa R
- Yang Jingyun
- Yao Jie
- Yousri Noha A
- Yu Lei
- Yuan Jian-Min
- Zemel Babette S
- Zeng Lingyao
- Zhang Liang
- Zhang Weihua
- Zhao Jing Hua
- Zhao Wei
- Zhou Jie
- Zonderman Alan B
- Publication venue
- Nature Communications
- Publication date
- 31/10/2020
- Field of study
Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding
Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies
- Author
- Aaron James Holland
- Abdullah Jumana T.
- Abrams Jonathan M.
- Abrashoff Riley
- Acevedo Andres B.
- Acha Iker
- Acosta Daniela M. Meza
- Adam Megan M.
- Adams Dante Q.
- Adams Elena R
- Adams Kalvyn N
- Akbar Zainab A.
- Akruwala Ushmi H.
- Al-Ghazwi Adel
- AlAbbas Batool H.
- Alahmed Mohammed S.
- AlAwadhi Areej A.
- Albakr Mohammed A.
- Albalushi Yusef J.
- Albaum Jonathan
- Aldhamen Ahmed
- Ales Nolan
- Alesmail Mohammad
- Alhabeeb Abdulelah
- Alhamli Dania
- AlHarbi Yazeed A.
- Alhuseini Isehaq
- Alkaabi Suhail
- Alkhezzi Tameem
- Alkubaisi Mohamed
- Allanqawi Nasser
- Allsbrook Martin
- Almohsen Yousef A.
- Almquist Justin Thomas
- Alnaji Teeb
- Alnasrallah Yousef A
- Alonzi Nicholas
- Alosaimi Meshal
- Alqabani Emeen
- Alrubaie Mohammad
- Alsinan Reema A.
- Altenbern Ava L.
- Altokhais Abdullah
- Alyami Saleh A.
- Ameijenda Federico
- Amer Hamzi
- Amos Meggan
- Anderson Hunter J.
- Andrew Carter
- Andringa Jesse C
- Angwin Abigail
- Aradhya Arvind J.
- Aramians Andrew
- Arango Camila Villamil
- Archibald Jack. W.
- Arias-Robles Brian A.
- Aryan Maryam
- Ash Kevin
- Astalos Justin
- Atchley-Rivers N. S.
- Augenstein Dakota N.
- Austin Bryce W.
- Avula Abhinav
- Aycock Matthew C.
- Baflah Abdulrahman A.
- Balaji Sahana
- Balajonda Brian
- Balcer Leo M
- Baldwin James O.
- Banda David J
- Bard Titus
- Barmore Abby
- Barnes Grant M.
- Barnhart Logan D. W.
- Barone Kevin M.
- Bartman Jessica L.
- Bassel Claire
- Bastias Catalina S
- Bat-Ulzii Batchimeg
- Batra Jasleen
- Battist Lexi
- Bay Joshua
- Beach Simone
- Beard Sara
- Beato Quinn I
- Beattie Ryan
- Beatty Thomas
- Beauprez Jacob N.
- Beck Lily
- Beck M. G.
- Becker Simone E.
- Behr Braden
- Behrer Timothy A.
- Beijer Joshua
- Belei Brennan J.
- Belknap Annelene L.
- Bell Aislyn
- Bence Caden
- Benke Evan
- Berhanu Naomi
- Berriman-Rozen Zachary D.
- Bertuccio Chrisanna
- Berv Owen A.
- Biediger Blaine B.
- Biehle Samuel J
- Billig Brennen
- Billingsley Jacob
- Billman Jayce A.
- Biron Connor J.
- Bisacca Gabrielle E.
- Blake Cassidy A.
- Blandon Guillermo
- Blevins Olivia
- Blouin Ethan
- Bodzianowski Michal
- Boeyink Taylor A.
- Bondar Matthew
- Bone Lauren
- Bonilla Alberto Espinosa de los Monteros
- Borelli William T
- Borgerding Luke R.
- Bowen Troy
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- Venegas Nancy Ortiz
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- Vogel Connor Maklain
- von Peccoz Charles B. Beck
- Von Reich Ferin J.
- Wagoner Michaela
- Wallace Logan
- Wallace Steven P.
- Waller Caroline
- Wang Chaoran
- Wang Hongda
- Wang Jiawei
- Warble Keenan
- Ward-Chene N. R. D.
- Watson James Adam
- Weber Robert J.
- Wegner Aidan B.
- Weigand Anthony A
- Weiner Amanda M.
- Werth Alexandra
- West Ayana
- West Colin G.
- Wexler Ethan Benjamin
- Wheeler Nicola H.
- White Jamison R.
- White Oliver S.
- White Zachary
- Whittall Lloyd C.
- Wickenden Evan
- Wilcove Isaac
- Wilkinson Blake C.
- Willard John S.
- Williams Abigail K.
- Williams Sajan
- Wilson Connor B.
- Wilson Evan M.
- Wilson John
- Wilson Orion K.
- Wilson Timothy R.
- Witkoff Briahn
- Wolfe Aubrey M.
- Wolle Jackson R.
- Wood Travis M.
- Woodard Aiden L.
- Woodraska Donald L.
- Wootten Katelynn
- Wu Mengyu
- Xiao Catherine
- Yang Jianing
- Yang Zhanchao
- Yegovtsev Nikolay
- Young Isabel
- Young Trenton J.
- Youngblood Allison A.
- Zenner Thomas
- Zhang Jiaqi
- zhang Jinhua
- Zhao Noah Y.
- Zhao Tiannie
- Zhao Tianwei
- Zhou Chongrui
- Ziebold Josh J
- Ziegler Lucas J.
- Zimmermann Ingrid H
- Zygmunt James C.
- Publication venue
- 'American Astronomical Society'
- Publication date
- 09/05/2023
- Field of study
Flare frequency distributions represent a key approach to addressing one of
the largest problems in solar and stellar physics: determining the mechanism
that counter-intuitively heats coronae to temperatures that are orders of
magnitude hotter than the corresponding photospheres. It is widely accepted
that the magnetic field is responsible for the heating, but there are two
competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To
date, neither can be directly observed. Nanoflares are, by definition,
extremely small, but their aggregate energy release could represent a
substantial heating mechanism, presuming they are sufficiently abundant. One
way to test this presumption is via the flare frequency distribution, which
describes how often flares of various energies occur. If the slope of the power
law fitting the flare frequency distribution is above a critical threshold,
α=2 as established in prior literature, then there should be a
sufficient abundance of nanoflares to explain coronal heating. We performed
>600 case studies of solar flares, made possible by an unprecedented number
of data analysts via three semesters of an undergraduate physics laboratory
course. This allowed us to include two crucial, but nontrivial, analysis
methods: pre-flare baseline subtraction and computation of the flare energy,
which requires determining flare start and stop times. We aggregated the
results of these analyses into a statistical study to determine that α=1.63±0.03. This is below the critical threshold, suggesting that Alfv\'en
waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The
Astrophysical Journal on 2023-05-09, volume 948, page 7
Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture.
- Author
- A Kiezun
- A. Pernille Hermann
- Aaron Kleinman
- Adrian Sayers
- Albert Hofman
- Albert V. Smith
- Alberto Rosello‐Diez
- Alexandra L. Joyner
- Alireza Moayyeri
- Andre G. Uitterlinden
- Andrea Z. LaCroix
- Angela Xuereb‐Anastasi
- Anke W. Enneman
- Beatrice Melin
- Bente L. Langdahl
- Beth Wilmot
- Bing Ge
- Brooke B. Gardiner
- C Medina‐Gomez
- C Xu
- CA Loomis
- Carl Wibom
- Carolina Medina‐Gómez
- Carrie M. Nielson
- CC Chang
- Celia L. Gregson
- Celia M. T. Greenwood
- Charles Farber
- Charles Kooperberg
- Charlotta Uggla
- Cheryl L. Ackert‐Bicknell
- Chia‐Ho Cheng
- Ching‐Ti Liu
- Chitra L. Dahia
- Chris Carlson
- CL Ackert‐Bicknell
- Claes Ohlsson
- Claus Christiansen
- Cornelia M. van Duijn
- Cynthia A. Loomis
- Dan Mellström
- Daniel Grinberg
- Daniel I. Chasman
- Daniel S. Evans
- David A. Hinds
- David Goltzman
- David Karasik
- David M. Evans
- David W. Rowe
- Denis Paquette
- DF Gudbjartsson
- DL Koller
- Dominique Gauguier
- Douglas P. Kiel
- D‐H Xiong
- EL Duncan
- Elin Grundberg
- Emma L. Duncan
- Eric S. Orwoll
- EV Davydov
- Evangelia E. Ntzani
- F Rivadeneira
- Fernando Rivadeneira
- Fiona E. McGuigan
- Fjorda Koromani
- Franco Giulianini
- François Rousseau
- Gaurav Garg
- George Davey‐Smith
- GR Abecasis
- Gregory J. Tranah
- Gudmar Thorleifsson
- Göran Hallmans
- H Li
- H Tang
- Hou‐Feng Zheng
- H‐F Zheng
- J Huang
- J Yang
- J. Brent Richards
- Jacqueline R. Center
- James Fraser
- JB Richards
- JB Richards
- Jeff Haessler
- Jens‐Erik B. Jensen
- Jeroen van Rooij
- Jie Huang
- Joel Eriksson
- Johanne Bussière
- John A. Eisman
- John P. Kemp
- Jonathan H. Tobias
- Jonathan Reeve
- Jose A. Riancho
- Jose M. Olmos
- Joshua R. Lewis
- Josine Min
- Josée Dostie
- Joyce B. J. van Meurs
- Joyce Y. Tung
- JR Dixon
- K Estrada
- Kari Stefansson
- Karol Estrada
- Katerina Trajanoska
- Katie Cremin
- Kay‐Tee Khaw
- Klaudia Walter
- Kristin Siggeirsdottir
- Kristina Åkesson
- Kwangbom Choi
- Kyung Hyun Park‐Min
- L. Adrienne Cupples
- LA Hindorff
- Lauren E. Mokry
- Lenore L. Launer
- Li Hsu
- Liesbeth Vandenput
- Ling Oei
- Lisette C. P. G. M. de Groot
- Lynda M. Rose
- M Adamska
- M Hanks
- M Ladouceur
- M. Carola Zillikens
- Magnus K. Karlsson
- Maria T. Zarrabeitia
- Matthew A. Brown
- Matthew A. Hibbs
- Matthew T. Maurano
- MC Wu
- Melina Claussnitzer
- Melissa M. Formosa
- Mhairi Marshall
- Mila Jhamai
- MP Matise
- Najaf Amin
- Natalia Garcia‐Giralt
- Natasja M. van Schoor
- Nathalie van der Velde
- Nerea Alonso
- Nicholas J. Timpson
- Nicole Soranzo
- Olle Svensson
- P Sulem
- Pascal P. Arp
- Paul Auer
- Paul J. Leo
- Paul M. Ridker
- Petr Danecek
- R Mägi
- RA Deckelbaum
- Rebecca D. Jackson
- Richard Durbin
- Richard L. Prince
- Robert Kraaij
- Rui Li
- S Movérare‐Skrtic
- Scott G. Wilson
- Shane McCarthy
- Shu‐Huang Chen
- SK Sgaier
- Soizik Berlivet
- Sophie Calderari
- Stephen Kaptoge
- Stephen R. Williams
- Stuart H. Ralston
- Sue Ring
- Sylvie Giroux
- Tamara B. Harris
- Tim Spector
- Tomi Pastinen
- Tony Kwan
- Tuan V. Nguyen
- U Styrkarsdottir
- U Styrkarsdottir
- U Styrkarsdottir
- Ulrika Pettersson‐Kymmer
- Ulrike Peters
- Unnur Styrkarsdottir
- Unnur Thorsteinsdottir
- Vilmunder Gudnason
- Vincenzo Forgetta
- W McLaren
- Warren Cheung
- Wen‐Chi Chou
- Xavier Nogues
- Xi Jiang
- Yanhua Zhou
- Yasin Memari
- Yi‐Hsiang Hsu
- Östen Ljunggren
- Publication venue
- Nature
- Publication date
- 01/01/2015
- Field of study
The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population
Teacher Competence
- Author
- Adams E. W.
- Adams E. W.
- Adams W. C. T.
- Adams W. C. T.
- Albert H. R.
- Allen H. P.
- Allen Hollis P.
- Almack J. C.
- Almack J. C.
- Almy H. V.
- An Editorial
- an Editorial
- an Editorial
- an editorial
- an editorial
- Andersen W. N.
- Anderson C. S.
- Anderson D. A.
- Anderson Vivienne
- Anderson M. E. and others
- Antell Henry
- Apgar Genevieve
- Archer C. P.
- Archer Clifford P.
- Archer Clifford P.
- Aretz C. W.
- Armstrong F. E.
- Arny C. B.
- Ashley V. S.
- Atkinson E. W.
- Austin S. Carolyn
- Baer J. A.
- Bagley W. C.
- Bain Winifred E.
- Baird James
- Baird J. and others
- Baker B. K.
- Baker F. E.
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- Ball L. B.
- Balliet T. M.
- Ballou F. W.
- Ballou F. W.
- Bamberger Florence E.
- Barr A. S.
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- Publication venue
- 'Vandenhoeck & Ruprecht GmbH & Co, KG'
- Publication date
- Field of study
New insights into the genetic etiology of Alzheimer’s disease and related dementias
- Author
- A David Smith
- Aaltonen L.
- Aaltonen V.
- Aarno Palotie
- Aarsland D.
- Aavikko M.
- Abalos M. S.
- Abdelnour C.
- Abner E.
- Abraham R.
- Ad Adarmes-Gómez
- Adam Boxer
- Adam Ziemann
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- Adams P. M.
- Adarmes-Gómez A.
- Adarmes-Gómez A. D.
- Adriana Gamboa
- Adrienne L Cupples
- Adrienne Tin
- Aguilera N.
- Aguilera N.
- Aguirre A.
- Agustina Legaz
- Ahmad S.
- Aimee Pierce
- Aino Salminen
- Airi Jussila
- Aisha Khaleeq
- Aki Havulinna
- Akinyemi R. O.
- Al-Chalabi A.
- Alan B Stevens
- Alan Lerner
- Alarcón-Martín E.
- Albert M. S.
- Alberto Benussi
- Albin R. L.
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- Aldo Saenz
- Alegret M.
- Alessandra Chesi
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- Thomas Wisniewski
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- Tiffany F Kautz
- Tiina Laatikainen
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- Veikko Salomaa
- Veli-Matti Kosma
- Venkat Subramaniam Rathinakannan
- Verhey F.
- Vesa Aaltonen
- Vicente M. P.
- Victor W Henderson
- Victoria Fernandez-Hernandez
- Victoria Perez
- Victoriana Martínez
- Vidal J. -S.
- Vigo-Ortega R.
- Vilas R. H.
- Vinay Mehta
- Vincent Deramecourt
- Vincent Deramerourt
- Vincent Llorens
- Vinters H. V.
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- Vivianna M Van Deerlin
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- Vonsattel J. -P.
- Voutilainen M.
- Vuokko Anttonen
- Vyhnalek M.
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- Wang C.
- Wang L. -S.
- Wang R.
- Wang Y.
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- Waring J.
- Warner N.
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- Waterworth D.
- Wayne C McCormick
- Wayne W Poon
- Weber H.
- Wei Gu
- Wei Zhou
- Weinhold L.
- Weinstein G.
- Weintraub S.
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- Whelan C.
- Whitehead P. L.
- Wichmann H. -E.
- Wigmore E.
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- Wilcock G.
- Wilhelmsen K. C.
- Will S Bush
- William Kremen
- William Nash
- William W Seeley
- Williams A.
- Williams B.
- Williams D.
- Williams J.
- Williamson J.
- Wilms H.
- Wiltfang J.
- Windle G.
- Wingo T. S.
- Wisniewski T.
- Wittfeld K.
- Woltjer R. L.
- Wong R.
- Woods B.
- Woon M.
- Wright C. B.
- Wu C. -K.
- Wu Y.
- Xia T. -H.
- Xing Chen
- Xinli Hu
- Xiongwei Zhu
- Xu E.
- Xu F.
- Xuan Liu
- Yanbing Wang
- Yanek L.
- Yang Q.
- Yang Y.
- Yannakoulia M.
- Yaqub A.
- Yasaman Saba
- Yash Patel
- Yeunjoo E Song
- Yi Zhao
- Ying Wu
- Yoav Ben-Shlomo
- Yogen Patel
- Younkin S. G.
- Yu C. -E.
- Yu L.
- Yuanchao Zhang
- Yuk Yee Leung
- Yunfeng Huang
- Yunju Yang
- Zare H.
- Zdenka Pausova
- Zhang X.
- Zhang Y.
- Zhao Y.
- Zhao Y.
- Zhou W.
- Zhu C.
- Zhu X.
- Ziemann A.
- Zoia C. P.
- Zompo M. D.
- Zulaica M.
- Zulma Sevillano
- Álvarez V.
- Åsa Hedman
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
Abstract
- Author
- Aaron D. Brown
- Aiala Barr
- Alain Gauthier
- Alan Cheng
- Alan Daly
- Alex Bohorquez
- Alexander S. Clanachan
- Alexandra Kirkley
- Alicia Kowalski
- Allan Bell
- Allaudin Kamani
- Andrew Baker
- Andrew J. Baker
- Angela Rocchi
- Anna Lee
- Anthony M. -H. Ho
- Anwar Morgan
- Atul Prabhu
- Ayman Hendy
- B. Anderson
- B. Lim
- B. S. Dhaliwal
- B. S. Dhaliwal
- Barry A. Finegan
- Barry A. Finegan
- Barry Finegan
- Bernard Hubert
- Bing Wang
- Bita Nasseri
- Brendan S. Barrett
- Brendan T. Finucane
- Brian G. Feagan
- Brian Milne
- Brian Milne
- Brian Milne
- Brian Muirhead
- Bruce D. Winegar
- C. David Mazer
- C. M. Ho
- Carmen Rivero Fuenmayor
- Carol Fiorilli
- Charles Imarengiaye
- Chris Loomis
- Cindy J. Wong
- Claudia Coimbra
- Craig H. Leicht
- Cristina Hurtado
- Cynthia L. Henderson
- D. John Doyle
- D. W. C. Johnston
- Damian Yung
- Dan Wood
- Daniel Boudreault
- David H. Goldstein
- David M. Ansley
- David Mazer
- David P. Archer
- David T. Raphael
- David V. Godin
- David Wong
- Davinia E. Withington
- Davy Cheng
- Debbie Tod
- Denis Babin
- Dimiter Arnaudov
- Dolores M. McKeen
- Dominique C. Girard
- Dominique Gauvin
- Donald T. Jolly
- Donna Clarke
- Donna Millington
- Doreen Cleave-Hogg
- Dorothy Thompson
- Douglas D. Snider
- Driss El-Kebir
- Duminda N. Wijeysundera
- Dy Nguyen
- Elaine Liu
- Elizabeth G. Van Den Kerkhof
- Elizabeth G. Van Den Kerkhof
- Elizabeth Ling
- Elizabeth Orr
- Emmanuel Kanetos
- Fadi Basile
- Fan Yang
- Finlay McAlister
- Frances Chung
- Francois Donati
- Frank C. Smith
- François Fugère
- François Girard
- François Plante
- Fred S. Mikelberg
- G. Allen Finley
- G. Doak
- G. Michael Davis
- Gary Dobson
- Geena Joseph
- George N. Djaiani
- Gilbert Blaise
- Glenn McGuire
- Gordana Dulovic
- Gregory M. T. Hare
- Guy Petroz
- Heather Lee Loughlin
- Henry Kuerer
- Hoi Kwan Lee
- Ian Gilron
- Ian Keith
- Ian R. Thomson
- Ignacio Prieto
- Isabelle Charest
- Ivan A. Velickovic
- J. Loiselle
- J. Patrick O’Connor
- J. Shannon
- Jacek M. Karski
- Jacelyn Kolman
- Jae Hang Shim
- Jan Paton
- Jayanta Muhkerji
- Jean Kronberg
- Jean Wong
- Jeffrey Barkun
- Jeffrey I. Freedman
- Jerrold Lerman
- Jessie A. Leak
- Jiri Hrazdil
- Jo A. Carroll
- Joachim Schmidt
- Joanne D. Fortier
- Joanne Douglas
- Joel L. Parlow
- John C. Galbraith
- John Doyle
- John F. Dolman
- John H. P. Friesen
- John Tchervenkov
- John V. Tyberg
- Jordan Tarshis
- Kaori Saito
- Kathryn M. Hum
- Kelly V. Mayson
- Ken Luk
- Keruyi Popat
- Kevin Teoh
- Keyvan Karkouti
- Kim Turner
- Klaus E. Jacobi
- Kyung Hun Kim
- Leah Jamnicky
- Linda Harris
- Lindy Forte
- Louie T. S. Wang
- Louie Wang
- Lucia Evans
- M. Denise Daley
- Manoj Gandhi
- Manon Choinière
- Margaret Srebrnjak
- Maria C. Greacen
- Mark Bernstein
- Mark Esler
- Mary Jane Salpeter
- Masao Yamashita
- Maxim Benbassat
- Meera Shah
- Michael Fehlings
- Michael Jacka
- Michael Jewett
- Michel-Antoine Perrault
- Michelle Chochinov
- Mike Rimmer
- Min Zhao
- Mohammed M. Ghannam
- Mohammed Shamsah
- Monique Ruel
- Murray Hong
- Mustafa Karamanoglu
- N. Persaud
- Naaznin Samanani
- Nancy Sikich
- Ngozi Imasogie
- Nicholas Phan
- Nicole D. Avery
- Nizar N. Mahomed
- Pamela Angle
- Pamela H. Lennox
- Pamela H. Lennox
- Pamela J. Morgan
- Patricia Amicone
- Patricia Morley-Forster
- Paul S. Bach
- Paul Serowka
- Paul Whitsitt
- Peter Duke
- Peter H. Norman
- Peter Metrakos
- Philippe Chouinard
- Pierre Beaulieu
- Ramiro Arellano
- René Martin
- Richard Hall
- Robert J. Hudson
- Robert T. Nunn
- Ruud A. W. Veldhuizen
- S. K. Tsai
- Saifundin Rashiq
- Sam Tang
- Samantha J. Woolsey
- Sandy Clanachan
- Sandy Shysh
- Sarah Hogervorst
- Sean Hall
- Shaheen Shaikh
- Sharon Davies
- Sheldon H. Roth
- Sherry Stewart
- Stephen Halpern
- Steve Y. Kim
- Steven B. Backman
- Stuart A. McCluskey
- Stuart McCluskey
- Sudha Singh
- Suntheralingam Yogendran
- Susan Buffett-Jerrott
- Susan Eveleigh
- T. AlAyed
- Tao Bui
- Ted Ashbury
- Teresa Valois Gomez
- Terrance A. Yemen
- Theodore E. Warkentin
- Thomas Dougherty
- Thomas Howlett
- Thomas K. H. Chang
- Thomas M. Hemmerling
- Tianlong Wang
- Toshimi Arai
- Una Srejic
- Vikki Wilkinson
- Vit Gunka
- Vivien Walsh
- W. Scott Beattie
- W. Scott Beattie
- Wendy C. E. Hall
- William G. Williams
- William Li Pi Shanl
- Woo Jae Jeon
- Woo Jong Shin
- Yoga R. Rampersaud
- Zhengyuan Xia
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study