25 research outputs found
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
- Author
- A Doria
- A Patel
- A Tirosh
- Abbas Dehghan
- AJ Myers
- AL Dixon
- Alan F Wright
- Alan R Shuldiner
- Albert Hofman
- Alex Doney
- Alisa K Manning
- Amanda Elliott
- Amanda J Bennett
- Amy Swift
- Amélie Bonnefond
- Andreas F H Pfeiffer
- Andrew A Hicks
- Andrew D Morris
- Andrew P Morris
- Andrew Singleton
- Andrew T Hattersley
- Andrew Walley
- André G Uitterlinden
- Angela Silveira
- Anke Tönjes
- Ann-Christine Syvänen
- Anna L Gloyn
- Anna-Liisa Hartikainen
- Anne U Jackson
- Anneli Pouta
- Annelli Sandbaek
- Annette C Fedson
- Antje Fischer-Rosinsky
- Antti Jula
- Anuj Goel
- Aroon D Hingorani
- Avan Aihie Sayer
- B Devlin
- B Lukowiak
- B Peter-Riesch
- B Servin
- Barbara Thorand
- Beatrice Knight
- Ben A Oostra
- Benjamin F Voight
- Beverley Balkau
- Beverley Shields
- Björn Zethelius
- Bo Isomaa
- Braxton D Mitchell
- Bruce M Psaty
- C Gieger
- C Newton-Cheh
- C Sabatti
- Carina Zabena
- Caroline Hayward
- Caroline S Fox
- Cecilia M Lindgren
- Christa Meisinger
- Christian Dina
- Christian Gieger
- Christian Herder
- Christine Cavalcanti-Proença
- Christopher J Groves
- Christopher S Franklin
- CJ Willer
- Claudia Langenberg
- Colin N A Palmer
- Cristian Pattaro
- Cyrus Cooper
- Cécile Lecoeur
- D Keane
- Daniel Pearson
- Danielle Posthuma
- David M Nathan
- David Melzer
- David Meyre
- David R Hillman
- Debbie A Lawlor
- Denis Rybin
- Dhiraj Varma
- Diana B. Petitti
- Diana Zelenika
- DJ Drucker
- DR Clemmons
- DR Matthews
- Eco J C de Geus
- EE Schadt
- Eleanor Wheeler
- Eleftheria Zeggini
- Eric Boerwinkle
- Eric Brunner
- Eric J G Sijbrands
- Erik Ingelsson
- Felicity Payne
- Fernando Rivadeneira
- Frank B Hu
- François Pattou
- Fredrik Karpe
- G Bragi Walters
- G Mark Lathrop
- G Waeber
- Gabe Crawford
- GC Weir
- George Davey Smith
- George V Dedoussis
- Ghislain Rocheleau
- Giuseppe Paolisso
- Gonneke Willemsen
- Gordon H Williams
- Guangju Zhai
- Gudmar Thorleifsson
- Guillaume Charpentier
- Gunnar Sigurðsson
- Gérard Waeber
- Göran Hallmans
- H Erich Wichmann
- Harald Grallert
- Harry Campbell
- Heather M Stringham
- Holly Syddall
- Hugh Watkins
- I Pe'er
- I Prokopenko
- I Prokopenko
- Ian N M Day
- Igor Rudan
- Inga Prokopenko
- Ingrid B Borecki
- Irene Pichler
- J Marchini
- J Rung
- Jaakko Kaprio
- James F Wilson
- James S Pankow
- Jaqueline C M Witteman
- Jarred B McAteer
- JB Meigs
- JC Florez
- JD Brunzell
- Jean Tichet
- Jeffrey O'Connell
- Jennie Hui
- Jerome Delplanque
- Jian'an Luan
- Jing Hua Zhao
- JJ Song
- Joachim Spranger
- Joe Hung
- Johanna Kuusisto
- John F Peden
- John P Beilby
- John R B Perry
- John W G Yarnell
- Josephine M Egan
- Joshua Randall
- Josée Dupuis
- Jouke Jan Hottenga
- JP Higgins
- JP Ioannidis
- Jürgen Graessler
- K Kume
- K Warton
- K Yamagata
- K-H Song
- Kaisa Silander
- Kenneth Rice
- Kijoung Song
- Kim L Ward
- Kirsten Ohm Kyvik
- KK Ray
- Knut Borch-Johnsen
- Ko Willems van Dijk
- Kristin Ardlie
- L Schaeffer
- Lachlan J M Coin
- Laila Simpson
- Lars Lind
- Laura Crisponi
- Laura J McCulloch
- Laura J Scott
- Lori L Bonnycastle
- Lu Qi
- Lyle J Palmer
- M Carola Zillikens
- M Coutinho
- M Orho-Melander
- M Prentki
- M Vaxillaire
- Man Li
- Mandy van Hoek
- Manjinder Sandhu
- Manuel Serrano-Ríos
- Marco Orrù
- Maria Grazia Franzosi
- Marika Kaakinen
- Marilyn Cornelis
- Mario A Morken
- Mark O Goodarzi
- Markku Laakso
- Markus Perola
- María Teresa Martínez-Larrad
- Massimo Mangino
- Matthew J Neville
- Matthew N Cooper
- Meena Kumari
- Michael A Province
- Michael J Sampson
- Michael Marmot
- Michael N Weedon
- Michael R Erdos
- Michael Roden
- Michael Stumvoll
- Mika Kivimaki
- MN Weedon
- MT Guillam
- Murielle Bochud
- N Bouatia-Naji
- N Bouatia-Naji
- N Mitro
- Nabila Bouatia-Naji
- Nancy L Pedersen
- Naomi Hammond
- Narisu Narisu
- Neelam Hassanali
- Nicholas J Timpson
- Nicholas L Smith
- Nicole L Glazer
- Nicole Soranzo
- Nicole Vogelzangs
- Niels Grarup
- Nigel W Rayner
- Nita G Forouhi
- NL Beer
- Olivier Le Bacquer
- Olov Rolandsson
- Oluf Pedersen
- Ozren Polasek
- P Rorsman
- Patrik K E Magnusson
- Pau Navarro
- Paul Elliott
- Paul R V Johnson
- Paul Scheet
- Paul W Franks
- PC Ng
- PD Thomas
- Peter Chines
- Peter Henneman
- Peter J Wagner
- Peter Kovacs
- Peter Paul Pramstaller
- Peter Schwarz
- Peter Shrader
- Philip Barter
- Pierre Meneton
- Pilar Galan
- Ping An
- Praveen Sethupathy
- R Santer
- Rafn Benediktsson
- RD Rudic
- Reedik Mägi
- Rhian Gwilliam
- Richa Saxena
- RN Bergman
- Robert Clarke
- Robert Mahley
- Rosa Maria Roccasecca
- RR Holman
- Rune Frants
- Ruth J F Loos
- Ruth McPherson
- Ruth Pakyz
- S Genuth
- S Kathiresan
- S Nejentsev
- S Raychaudhuri
- S Sunyaev
- SA McCarroll
- Samuli Ripatti
- Samy Hadjadj
- Sarah H Wild
- Scott Grundy
- Seppo Koskinen
- Serena Sanna
- Serge Hercberg
- Shah Ebrahim
- Silvia Naitza
- Simon C Heath
- Simon C Potter
- Sophie Visvikis-Siest
- Stavroula Kanoni
- Stefan R Bornstein
- Stephen J Sharp
- Steven A McCarroll
- Sutapa Mukherjee
- Suzannah J Bumpstead
- Sven Bergmann
- T Fukada
- T Sparsø
- Taina Lajunen
- Thomas Illig
- Thomas Sparsø
- Tiinamaija Tuomi
- Toby Johnson
- Torben Hansen
- Torben Jørgensen
- Toshiko Tanaka
- Udo Seedorf
- Ulf Gyllensten
- Ulla Sovio
- V Lyssenko
- V Senée
- Valeriya Lyssenko
- Valgerdur Steinthorsdottir
- Veikko Salomaa
- Veronique Vitart
- W H Linda Kao
- W-M Chen
- Wolfgang Rathmann
- Xijing Han
- Y Antero Kesaniemi
- Y Li
- Y-S Kim
- Yavuz Ariyurek
- Yii-Der Ida Chen
- Yoav Ben-Shlomo
- YS Aulchenko
- YS Aulchenko
- Yun Li
- Yvonne Böttcher
- Publication venue
- Nature Research
- Publication date
- 14/10/2009
- Field of study
Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes
Whole-genome sequencing reveals host factors underlying critical COVID-19
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- Abd Elghafar M. S.
- Abdel-Aziz M.
- Abdelrazik M.
- Abdollahi H.
- Abdullah T.
- Abecasis G. R.
- Abedalthagafi M.
- Abel L.
- Abernathy C.
- Abraheem A.
- Abul-Husn N. S.
- Acquilini D.
- Adams C.
- Adams E. L.
- Adams K.
- Adamsara A.
- Adanini O.
- Adeleye O.
- Adra D.
- Afilalo J.
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- Afolabi D.
- Afrasiabi Z.
- Agasou A.
- Agrawal S.
- Aguero D.
- Ahmad N.
- Ahmadi S.
- Ahmed A.
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- Akeroyd L.
- Akhtar M. N.
- Akinkugbe O.
- Aksentijevich A.
- Al-Afghani H.
- Al-Awdah L.
- Alaamery M.
- Alahmadey Z. Z.
- Alaverdian D.
- Alavere H.
- Albader A.
- Albaiceta G. M.
- Albakri J. K.
- AlBardis H.
- Albeladi M.
- Albesher N.
- Albrich W.
- AlDhawi N.
- Aldridge J.
- Aleagha A. E.
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
Microbial community structure mediates response of soil C decomposition to litter addition and warming
- Author
- Alexandre B. de Menezes
- Allison
- Allison
- Allison
- Allison
- Auyeung
- Ayres
- Baldock
- Baldock
- Baldock
- Baldock
- Balser
- Balser
- Bardgett
- Bauer
- Bengtson
- Billings
- Bird
- Blagodatskaya
- Bol
- Butler
- Chen
- Clarke
- Cleveland
- Cleveland
- Collins
- Conant
- Conant
- Coplen
- Coplen
- Courtney A. Creamer
- Craine
- Craine
- Curtis
- Cusack
- Cusack
- De Graaff
- De Menezes
- De Troyer
- De Vries
- De Vries
- Dijkstra
- Dilly
- Dungait
- Evelyn S. Krull
- Feng
- Feng
- Fernandez
- Fernández-Martínez
- Fierer
- Fierer
- Fontaine
- Fontaine
- Freschet
- Frey
- Frey
- Frostegård
- Frostegård
- Frostegård
- Garcia-Pausas
- Giardina
- Gleixner
- Gude
- Guenet
- Hagerty
- Hobbie
- Hopkins
- Hopkins
- Jonathan Sanderman
- Kaiser
- Kalbitz
- Kemmitt
- Klamer
- Knorr
- Kramer
- Kramer
- Krull
- Kögel-Knabner
- Lal
- Lane
- Lane
- Lau
- Lefèvre
- Li
- Li
- Liang
- Mack
- Malik
- Manzoni
- Manzoni
- Manzoni
- Mark Farrell
- Marschner
- Melillo
- Melillo
- Miltner
- Miranda
- Moorhead
- Moorhead
- Mulvaney
- Muyzer
- Neff
- Nie
- Paterson
- Paul
- Pendall
- Pregitzer
- Prior
- R Development Core Team
- Ramette
- Rinnan
- Rosa Newton-Walters
- Rousk
- Ruess
- Sanderman
- Schimel
- Schimel
- Schimel
- Schimel
- Schindlbacher
- Simpson
- Sollins
- Stone
- Strickland
- Strickland
- Sukharnikov
- Suseela
- Taylor
- Thiet
- Throckmorton
- Tucker
- Vitousek
- Von Lützow
- Waldrop
- Waldrop
- Wardle
- Wei
- White
- Wickings
- Wieder
- Wild
- Wixon
- Xiong
- Yuste
- Zelles
- Zhou
- Ziegler
- Zogg
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2015
- Field of study
Microbial activity has been highlighted as one of the main unknowns controlling the fate and turnover of
soil organic matter (SOM) in response to climate change. How microbial community structure and
function may (or may not) interact with increasing temperature to impact the fate and turnover of SOM,
in particular when combined with changes in litter chemistry, is not well understood. The primary aim of
this study was to determine if litter chemistry impacted the decomposition of soil and litter-derived
carbon (C), and its interaction with temperature, and whether this response was controlled by microbial
community structure and function. Fresh or pre-incubated eucalyptus leaf litter (13C enriched) was
added to a woodland soil and incubated at 12, 22, or 32 �C. We tracked the movement of litter and soilderived
C into CO2, water-extractable organic carbon (WEOC), and microbial phospholipids (PLFA). The
litter additions produced significant changes in every parameter measured, while temperature, interacting
with litter chemistry, predominately affected soil C respiration (priming and temperature sensitivity),
microbial community structure, and the metabolic quotient (a proxy for microbial carbon use
efficiency [CUE]). The direction of priming varied with the litter additions (negative with fresh litter,
positive with pre-incubated litter) and was related to differences in the composition of microbial communities
degrading soil-C, particularly gram-positive and gram-negative bacteria, resulting from litter
addition. Soil-C decomposition in both litter treatments was more temperature sensitive (higher Q10)
than in the soil-only control, and soil-C priming became increasingly positive with temperature. However,
microbes utilizing soil-C in the litter treatments had higher CUE, suggesting the longer-term stability
of soil-C may be increased at higher temperature with litter addition. Our results show that in the
same soil, the growth of distinct microbial communities can alter the turnover and fate of SOM and, in
the context of global change, its response to temperature
Evaluation of appendicitis risk prediction models in adults with suspected appendicitis
- Author
- Abbas Sh
- Abbas Sh
- Abbassi Oa
- Abbott T
- Abdelgadir Am
- Abdelrahman A
- Abdelrahman M
- Abdelrahman M
- Abdelwahed A
- Abellan M
- Abellán Am
- Abellán Am
- Abulafi M
- Acharya A
- Acosta A
- Adam Me
- Adams Re
- Adegbola So
- Adegbola So
- Adimonye A
- Adnan M
- Afshar S
- Agresta F
- Agua Ia
- Aguayo Jl
- Agudo Ar
- Ahad A
- Ahel J
- Ahern Dp
- Ahmad A
- Ahmed B
- Ahmed G
- Ahmed Os
- Ahmed Os
- Ahmed S
- Ainsworth P
- Ais G
- Ais G
- Aisoni F
- Akbari K
- Akhtar K
- Akinsola O
- Akram F
- Al-Faham Z
- Al-Khafaji N
- Al-Khyatt W
- Al-Musawi S
- Al-Sarireh B
- Al-Sheikh M
- Alagna V
- Alani M
- Alberca-Paramo A
- Aldrey I
- Alexander R
- Alhammali T
- Alhammali T
- Ali M
- Aljorfi A
- Allen M
- Allington J
- Alonzo A
- Alshafei A
- Altomare Ma
- Alvarez Cm
- Alvarez E
- Alvarez-Gallego M
- Amaducci E
- Amarasinghe R
- Amayo A
- Ambrona-Zafra D
- Amin V
- Ammendola M
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- Amtul N
- Amuthalingam T
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- Anania G
- Anania M
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- Anderson O
- Andolfi E
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- Andreani Sm
- Andrews B
- Ang A
- Ang A
- Angelieri D
- Angelini M
- Angrisani M
- Anguita F
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- Ansari A
- Aravind B
- Archer Je
- Arcuri Ga
- Arcuri Ga
- Aremu Ma
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- Aresu S
- Aresu S
- Argenio G
- Argenti F
- Armellini A
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- Arunachalam S
- Arunachalam S
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- Asensio-Gomez L
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- Ashour O
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- Asmadi Aa
- Assaf N
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- Assaf N
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- Avalapati H
- Avanzolini A
- Avanzolini A
- Awokoya Oo
- Ayllón-Gámez S
- Ayube-Brown J
- Azabdaftari A
- Azevedo J
- Azevedo Jm
- Baddams Ts
- Badenoch T
- Badii B
- Badran A
- Baeza-Murcia M
- Bagga R
- Baginski A
- Bailey Ja
- Bailey S
- Bailey S
- Bailon-Cuadrado M
- Baird C
- Bairos F
- Baker B
- Balai Ej
- Balasubramaniam A
- Balestra F
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- Ball A
- Ball A.
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- Ballester Mm
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- Bansal H
- Baraghini M
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- Bawa S
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- Bazán-Hinojo Mc
- Bazán-Hinojo Mc
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- Beral D
- Beral D
- Bernal-Sprekelsen Jc
- Berry B
- Berti S
- Bevan Ke
- Bevan V
- Beverstock A
- Bhanderi S
- Bhanderi S
- Bhanderi S
- Bhanderi S
- Bhanderi S.
- Bhangu A. Nepogodiev D
- Bhangu A
- Bhangu A
- Bhangu A
- Bhangu A
- Bhargava A
- Biancafarina A
- Biancafarina A
- Bianchi Cl
- Bianchi Cl
- Bianco A
- Bilku D
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- Birindelli A
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- Blake L
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- Blencowe Ns
- Boddy Ap
- Boereboom C
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- Bolton W
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- Bond S
- Bond-Smith G
- Bondurri A
- Bonfante P
- Bonomo M
- Borg Cm
- Borges Fc
- Borghi F
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- Boshier Pr
- Botelho P
- Bowen J
- Bowerman H
- Bowley D
- Bowman Cr
- Bowman Cr
- Boyd-Carson H
- Boza K
- Bradshaw Cj
- Branagan G
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- Bravo-Gutiérrez Af
- Brennan S
- Brett M
- Brewer H
- Brewer Hk
- Brewer Hk
- Brews R
- Brien Jo
- Bronder C
- Brown A
- Brown Ag
- Brown Ce
- Brown Ce
- Brown Ce
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- Brown M
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- Brown R
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- Brunelli Db
- Bryan Es
- Buckley-Jones S
- Bukhari W
- Bull C
- Bullivant Jk
- Burke J
- Burns Km
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- Caballero A
- Caldeira Ab
- Caldwell M
- Callan R
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- Cameron Fc
- Campagnaro T
- Campagnaro T
- Campbell U
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- Campbell W
- Cannata G
- Cannavò M
- Cantafio S
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- Carcoforo P
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- Carder C
- Cardona R
- Cardoso D
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- Carney K
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- Carrano Fm
- Carrano Fm
- Cartwright H
- Carvalho Lc
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- Casimiro C
- Castagnoli G
- Castagnoli G
- Caula C
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- Cavallo D
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- Cerdán-Santacruz C
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- Cervellera M
- Cesari Mc
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- Chandratreya N
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- Charalabopoulos A
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- Chauhan P
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- Chauhan P.
- Cheah Wl
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- Cheng Sa
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- Chessa A
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- Chianese G
- Chillitupa Cz
- Chimetto A
- Chin My
- Chishti Ia
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- Chng S
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- Choong Jh
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- Zorrilla L
- Zuin M
- Zurleni Tz
- Publication venue
- 'Wiley'
- Publication date
- 01/01/2019
- Field of study
Background
Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis.
Methods
A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis).
Results
Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent).
Conclusion
Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M.S.
- Abdel-Aziz M.
- Abdelrazik M.
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- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 07/07/2022
- Field of study
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
Corrigendum to “Microbial community structure mediates response of soil C decomposition to litter addition and warming” [Soil Biol. Biochem. 80 175–188]
- Author
- Publication venue
- 'Elsevier BV'
- Publication date
- Field of study
Mapping the human genetic architecture of COVID-19
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2021
- Field of study
The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease
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Risk of COVID-19 after natural infection or vaccinationResearch in context
- Author
- Abad Vanessa
- Abate Getahun
- Abbas Anum
- Ackerman Jamie
- Ackerman Ronald
- Ackermann Jeremy
- Adams Atoya
- Adams Mark S.
- Adams Michael R.
- Adelglass Jeffrey
- Afework Sarah
- Ahmad Nina
- Akamine Christine
- Ake Julie A.
- Al-Ibrahim Mohamed S.
- Albert Gary
- Alcaide Maria L.
- Alderson Nathan
- Aleman Lily
- Alemán José O.
- Allaw Mohammed
- Alva E. Javier Pretell
- Alvarado Hilario
- Amador Carmen
- Andersen James
- Anderson Corey G.
- Anderson Evan J.
- Anderson Victoria R.
- Andes David R.
- Andrasik Michele P.
- Andree Stephanie
- Andrews Jeb
- Andriesen Jessica G.
- Andriulis Victoria
- Ansel Jessica L.
- Anthony Codi M.
- Antwi Mohammed
- Arduino Roberto C.
- Aristy Florida
- Arnold Valerie K.
- Arrazcaeta Alicia
- Atmar Robert L.
- Avworo Ayoade
- Bacher Christina
- Baden Lindsey R.
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- Bernard Marcia
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- Tong Xiaomi
- Torres Juan P.
- Torres Julian A.
- Tovar Dalia
- Tran Carolyn
- Treanor John J.
- Tukuru Sade
- Turley Christine B.
- Turner Mark A.
- Tyson Stefanie
- Ulrich Robert J.
- Usdan Lisa S.
- Utz Gregory C.
- Vachris Timothy P.
- Valenti Bruno
- Valika Insiya
- Van Der Leden Mimi
- Van Dromme Ilse
- Van Ever Wesley
- Van Roey Griet
- Varughese Tilly
- Vega Jocelyn Zuleica Olmos
- Vega Norma
- Vegas Diana
- Vertucci Michele
- Viar Veronica
- Viens Nicholas A.
- Villegas Marysol
- Vingerhoets Johan
- Vogler Mary
- Vowell Mandy
- Vrbicky Keith W.
- Wahlin Tami
- Wakefield Paul H.
- Wald Anna
- Walker James
- Walker Shannon
- Walsh Edward E.
- Walsh Mary C.
- Walsh Stephen R.
- Walsh Stephen R.
- Walter Emmanuel B.
- Walters Ayanna
- Wang Tina
- Warden Ashley
- Waters Michael
- Watkins Breanz
- Webb Angella
- Webster Hala
- Weidler Jessica L.
- Weiss Thomas
- Wells Margaret
- Wendell Lewis III
- Wendrow Andrea
- Werne Melody
- West Whitney
- Whatley Jordan L.
- Whitaker Jennifer A.
- White Jewel J.
- White Julie
- White Toni
- Wijewardane Priyantha N.
- Wilkin Timothy
- Wilkinson Bethanie
- William S. Davis Jr
- Williams Barton G.
- Williams Hayes
- Williams Samantha
- Wilson Christine
- Wilson Clint
- Wilson Greg
- Wilson Natasha
- Winbigler Jennifer
- Winkle Peter J.
- Winokur Patricia L.
- Witbeck John
- Wohl David
- Woo Wayne
- Woodside Leana
- Wortman Glenn
- Wu Yi H.
- Wylie Paul E.
- Yang Fan
- Yang Kinara S.
- Yoon Anelgine C.
- York Jill
- Young Cheryl
- Yu Chenchen
- Yusin Joseph
- Zapata Luz
- Zash Rebecca
- Zegarra Eneyda Giuvanela Llerena
- Zemanek Arthur L.
- Zenlea Kate
- Zepeda Karla
- Zervos Marcus J.
- Zhai Nan
- Zhang Kevin
- Zhou James
- Zimmer Andrea
- Zingman Barry S.
- Zorrilla Carmen D.
- Áñez Germán
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/10/2023
- Field of study
Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health
Risk of COVID-19 after natural infection or vaccinationResearch in context
- Author
- A. Lina Rosengren
- Abram Burgher
- Adam B. Brosz
- Adam Rosen
- Adam Schwartz
- Adriana Sordo Duran
- Adrienna Marquez
- Adrienne E. Shapiro
- Aeiress Duhart
- Afsoon Roberts
- Albert Liu
- Alejandro Hoberman
- Alejandro Quintín Barrat Hernández
- Alex Greninger
- Alexander Clark
- Alfredo Gilberto Guerreros Benavides
- Alice McGarry
- Alicia Arrazcaeta
- Alisha Lutat
- Alison Bondell
- Alison Pellecchia
- Allie Oplinger
- Allison Green
- Allison O'Brien
- Alpa Patel
- Alyssa-Kay Peay
- Amanda Horn
- Amanda Lilienthal
- Amanda Occhino
- Amanda Philyaw
- Amaran Moodley
- Amber Grant
- Amber Stanford
- Amesika Nyaku
- Amie Shannon
- Amina Z. Haggag
- Amit Paliwal
- Amy Caldwell
- Amy Chamberlain
- Amy Dye
- Amy Falk
- Amy Kelley
- Amy Medina
- Amy Potts
- Amy Salzl
- Amy Sherman
- Amy Starr
- Amy Thompson
- Andrea Berry
- Andrea Clement
- Andrea Wendrow
- Andrea Zimmer
- Andres Bran
- Andres Camacho-Gonzalez
- Andrew Lauria
- Andrew McConnell
- Andrew McWilliams
- Anelgine C. Yoon
- Angela Lee
- Angela R. Branche
- Angelica Kottkamp
- Angella Webb
- Ann M. Milliken
- Ann R. Falsey
- Anna S. Lok
- Anna Wald
- Anne Marit de Groot
- Anne-Marie Rick
- Annette R. Bennett
- Annie Ciambruschini
- Annie Luetkemeyer
- Anthony Kim
- Anum Abbas
- Anyela Lara
- April Pixler
- Ariana C. Stanton
- Arthur L. Zemanek
- Asha Inniss
- Ashley Kennedy
- Ashley Perez
- Ashley Warden
- Asif Noor
- Atoya Adams
- Aurelio Cruz-Valdez
- Austin Chan
- Austin Swanson
- Ayanna Walters
- Ayoade Avworo
- Bailey Jordan
- Barbara Corral
- Barbara Rizzardi
- Barbara Rizzardi
- Barbara S. Taylor
- Barry S. Zingman
- Barton G. Williams
- Beatriz Grinsztejn
- Becky Martinez
- Ben Ladner
- Benjamin Eckhardt
- Benjamin J. Luft
- Bernard Grunstra
- Beth Safirstein
- Bethanie Wilkinson
- Beverly E. Sha
- Beverly Ewing
- Bindu Balani
- Blanca Gomez
- Bo Shopsin
- Boerries Brandenburg
- Brandie Taylor
- Brandon J. Essink
- Brandy Ball
- Breanz Watkins
- Brenda Dorcely
- Brendan Levy
- Brett Gray
- Brett Leav
- Brian D.W. Chow
- Brit Sovic
- Brittany Feijoo
- Brittany Stewart
- Bruce C. Gebhardt
- Bruce G. Rankin
- Bruce McClenathan
- Bruno Valenti
- Bryan Gordon
- C. Mary Healy
- Caitlin J. Guiney
- Caitlin Moran
- Candace Smith
- Candice Montros
- Carina A. Rodriguez
- Carl Fichtenbaum
- Carl P. Griffin
- Carlos A. Fierro
- Carlos del Rio
- Carlos Lopez
- Carlos Malvestutto
- Carmel B. Dyer
- Carmen A. Paez
- Carmen Amador
- Carmen D. Zorrilla
- Carmen Medina
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- Carol Kauffman
- Carol L. Mitchell
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- Caroline Greene
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- Carolyn Tran
- Carrie Johnston
- Carrie Sopher
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- Catherine Mary Healy
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- Charles Harper
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- Charlotte-Paige Rolle
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- Chelsea Miles
- Chelsie Nutsch
- Chelsie Nutsch
- Chen S. Tan
- Chenchen Yu
- Cheryl Nuss
- Cheryl Young
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- Chinar Desai
- Christian Tomaszewski
- Christina A. Rostad
- Christina Bacher
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- Christine Akamine
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- Christopher Carpenter
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- Clint Wilson
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- Ruth Paiano
- Ruth S. Pinilla
- Ryan C. Maves
- Ryan Israelsen
- Ryan Little
- Ryan P. Starr
- Ryan Tomlinson
- S. Hasan Naqvi
- Saadia Khizer
- Sabina Raja
- Sade Tukuru
- Sally Eppenbach
- Samantha Williams
- Samira Shairi
- Sandra Erickson
- Sandra Janeth Ortega Domínguez
- Sandra Kelman
- Sandra Shelton
- Sarah Afework
- Sarah Dzigiel
- Sarah E. Rutstein
- Sarah Galloway
- Sarah Gordon
- Sarah M. Ingalsbe-Geno
- Sarah Omodele
- Satoshi Kamidani
- Sauda Muhammad
- Scott Borgetti
- Scott Kahney
- Scott N. Syndergaard
- Sebastian Garcia Escallon
- Secia Díaz-Miralrio
- Sergio E. Recuenco
- Sha-Wanda Richmond
- Shamika Huskey
- Shana Harshell
- Shanda Gower
- Shane G. Christensen
- Shannen Seversen
- Shannon Rodman
- Shannon Walker
- Sharine Phan
- Sharita Tedder-Edwards
- Sharon A. Riddler
- Sharon E. Frey
- Sharon Kohrs
- Sharon Nachman
- Sharzhaad Molina Guizar
- Shashi Kapadia
- Shauna H. Gunaratne
- Sheetal Kandiah
- Shelby Olds
- Shelby Pickle
- Sherif Naguib
- Sherrie Baker
- Sherry Lamberth
- Sheryl L. Henderson
- Shireen H. Jaffer
- Shishir K. Khetan
- Shivanjali Shankaran
- Shobha Swaminathan
- Sigridh Muñoz-Gómez
- Siham Mahgoub
- Sikhongi Phungwayo
- Silvano Omar Martínez Pérez
- Simbarashe G. Takuva
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- Sinikka L. Green
- Sonal Munsiff
- Sonia Guerrero
- Sonja Neumeister
- Spyros A. Kalams
- Srilatha Edupuganti
- Stacy Ford
- Stacy Slechta
- Stanford Plavin
- Stefanie Mott
- Stefanie Tyson
- Stephan C. Sharp
- Stephan Hong
- Stephanie Andree
- Stephanie Rolsma
- Stephanie Skipper
- Stephanie Sterling
- Stephen A. Spector
- Stephen Daniels
- Stephen Morris
- Stephen R. Walsh
- Stephen R. Walsh
- Steve Clemons
- Steven E. Carsons
- Steven Palmer
- Steven Shinn
- Steven Shoptaw
- Steven Sperber
- Stuart H. Cohen
- Surisday Mederos
- Susan Jeanfreau
- Susan Kline
- Susan L. Koletar
- Susan Parker
- Susanne Doblecki-Lewis
- Suzanna Studdard
- Suzanne Fiorillo
- Suzanne Gharib
- Suzanne Swan
- Sybil G. Hosek
- Szheckera Fearon
- Tamara Richards
- Tambra Dora
- Tameika Scott
- Tami Wahlin
- Tammi L. Shlotzhauer
- Tana Bourgeois
- Tanya Hutchins
- Taryn Petty
- Tatiana Beresnev
- Tavane Harrison
- Taylor Nelson
- Teletha Gipson
- Teresa A. Batteiger
- Teresa Becker
- Teresa Deese
- Teresa S. Sligh
- Teri Thompson-Seim
- Terri Moye
- Terry D. Klein
- Terry L. Poling
- Terry Piedra
- Theresa Hegmann
- Thomas B. Campbell
- Thomas C. Klein
- Thomas C.S. Martin
- Thomas Mellman
- Thomas Patterson
- Thomas Weiss
- Tiffany Esinhart
- Tiffany Nemecek
- Tiffany Schwasinger-Schmidt
- Tilly Varughese
- Timothy J. Hatlen
- Timothy P. Vachris
- Timothy Shope
- Timothy W. Schacker
- Timothy Wilkin
- Tina Tong
- Tina Wang
- Toby Briskin
- Todd Simmons
- Tom Fiel
- Toni Robinson
- Toni White
- Tracy Okonya
- Tracy R. Klein
- Trina L. Reynolds
- Troy Holdeman
- Tyler D. Bold
- Uriel R. Felsen
- Valentine M. Ebuh
- Valeria D. Cantos
- Valerie K. Arnold
- Vanessa Abad
- Vanessa Raabe
- Veronica G. Fragoso
- Veronica Garcia-Fragoso
- Veronica Procasky
- Veronica Viar
- Vicki E. Miller
- Vickie Leathers
- Victoria Andriulis
- Victoria Engler
- Victoria Mosteller
- Victoria R. Anderson
- Vida Veronica Ruiz Herrera
- Vincent Huynh
- Vincent Mirkil
- Vivek Rajasekhar
- Viviana Gonzalez
- Vladimir Berthaud
- Walter Patton
- Wanda Ramon
- Waseem Chughtai
- Wayne L. Harper
- Wayne Woo
- Wendell Lewis
- Wendell Lewis III
- Wendy A. Keitel
- Wesley Campbell
- Wesley Van Ever
- Westly Keating
- Whitney West
- Will Hernandez
- William B. Davis
- William B. Smith
- William H. Jones
- William Jennings
- William Kirby
- William P. Silver
- William R. Hartman
- William S. Davis Jr.
- William Schnitz
- William Seger
- Winniberg Stephany Alvarez León
- Winston Cavert
- Xiaomi Tong
- Yaa D. Oppong
- Yi H. Wu
- Ying Huang
- Yogesh K. Paliwal
- Youyi Fong
- Yunda Huang
- Yunda Huang
- Yvonne Davis
- Zachary Bittner
- Zainab Rizvi
- Zindy Yazmín Zárate Hinojosa
- Zudi-Mwak Takizala
- Publication venue
- Elsevier
- Publication date
- 01/10/2023
- Field of study
Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health
Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
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- Publication venue
- 'BMJ'
- Publication date
- 01/01/2021
- Field of study
Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis. Setting Prospective, international, multicentre, observational cohort study. Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative). Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality. Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787). Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups. Trial registration number NCT0432364