61 research outputs found
International Fisheries Management: A Comparative Analysis of Legal Approaches to Management in the Context of Polar Fisheries Regimes
- Author
- Publication venue
- Schulich Law Scholars
- Publication date
- 01/10/1999
- Field of study
This thesis examines the management of marine living resources in international law. The thesis considers the development of the two principal approaches to fisheries management. The first approach is based upon maximising the yield of particular stocks, and is reflected in the content of the 1982 United Nations Convention on the Law of the Sea. It has evolved out of fisheries management theory developed since the 1950s, and focuses upon extracting the maximum harvest of a particular stock while still permitting that stock\u27s biological regeneration. The second approach uses the precautionary principle, and may include management directed at the entire ecosystem. This approach has derived from international environmental law over the last twenty years, and based upon risk assessment, where if an action is proposed, the onus is placed on the proponent to demonstrate that the risk of damage falls within established parameters. The thesis explores the juridical bases of these approaches and charts their development. It then seeks to compare the approaches on a number of criteria through the media of two international conventions, operating in analogous polar environments. The first of these arrangements is the Bering Sea Doughnut Hole Convention, designed to preserve the pollock stock in the central area of the Bering Sea, and the second is the Convention for the Conservation of Antarctic Marine Living Resources (CCAMLR), designed to manage all the elements of the marine ecosystem of the Southern Ocean. The thesis concludes by rationalising the comparative analysis, and noting the difficulties common to both approaches in the area of compliance. It then proposes a number of mechanisms by which the management of stocks could be improved
The Parallel Rural Community Curriculum: is it a transferable model?
- Publication venue
- Publication date
- 01/01/2003
- Field of study
Deaki
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Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis
- Author
- Albert Marilyn S.
- Albin Roger L.
- Alkaade Samer
- Amann Stephen T.
- Anderson Michelle A.
- Apostolova Liana G.
- Arnold Steven E.
- Baillie John
- Baldwin Clinton T.
- Banks Peter A.
- Barber Robert
- Barmada M. Michael
- Barnes Lisa L.
- Beach Thomas G.
- Beecham Gary W.
- Beekly Duane
- Bennett David A.
- Bigio Eileen H.
- Bird Thomas D.
- Blacker Deborah
- Boxer Adam
- Brand Randall E.
- Burke James R.
- Buxbaum Joseph D.
- Cairns Nigel J.
- Cantwell Laura B.
- Cao Chuanhai
- Carney Regina M.
- Carroll Steven L.
- Chui Helena C.
- Clark David G.
- Conwell Darwin
- Cotton Peter B.
- Coté Gregory A.
- Cribbs David H.
- Crocco Elizabeth A.
- Cruchaga Carlos
- DeCarli Charles
- Demirci F. Yesim
- Devlin Bernie
- Dick Malcolm
- Dickson Dennis W.
- DiSario James
- Duara Ranjan
- Ertekin-Taner Nilufer
- Faber Kelley M.
- Fallon Kenneth B.
- Farlow Martin R.
- Farrer Lindsay A.
- Ferris Steven
- Foroud Tatiana M.
- Forsmark Chris E.
- Frosch Matthew P.
- Galasko Douglas R.
- Ganguli Mary
- Gardner Timothy B.
- Gearing Marla
- Gelrud Andres
- Geschwind Daniel H.
- Ghetti Bernardino
- Gilbert John R.
- Gilman Sid
- Glass Jonathan D.
- Goate Alison M.
- Graff-Radford Neill R.
- Green Robert C.
- Greenhalf William
- Growdon John H.
- Guda Nalini M.
- Haines Jonathan L.
- Hakonarson Hakon
- Hamilton Ronald L.
- Hamilton-Nelson Kara L.
- Harrell Lindy E.
- Hartman Douglas J.
- Hawes Robert A.
- Head Elizabeth
- Honig Lawrence S.
- Hulette Christine M.
- Hyman Bradley T.
- Jicha Gregory A.
- Jin Lee-Way
- Johnstone Marianne
- Jun Gyungah
- Kamboh M. Ilyas
- Karydas Anna
- Kaye Jeffrey A.
- Kienholz Michelle L.
- Kim Ronald
- Klei Lambertus
- Koo Edward H.
- Kowall Neil W.
- Kramer Joel H.
- Kramer Patricia
- Krasinskas Alyssa M.
- Kukull Walter A.
- LaFerla Frank M.
- Lah James J.
- LaRusch Jessica
- Lawrence Christopher
- Lerch Markus M.
- Leverenz James B.
- Levey Allan I.
- Lewis Michele
- Li Ge
- Lieberman Andrew P.
- Lin Chiao-Feng
- Lopez Oscar L.
- Lunetta Kathryn L.
- Lyketsos Constantine G.
- Mack Wendy J.
- Marson Daniel C.
- Martin Eden R.
- Martiniuk Frank
- Mash Deborah C.
- Masliah Eliezer
- Mayerle Julia
- Mayeux Richard
- McKee Ann C.
- Melhem Nadine M.
- Mesulam Marsel
- Miller Bruce L.
- Miller Carol A.
- Miller Joshua W.
- Money Mary E.
- Montine Thomas J.
- Morris John C.
- Muniraj Thiruvengadam
- Murrell Jill R.
- Naj Adam C.
- Neoptolemos John P.
- O'Connell Michael R.
- Olichney John M.
- Orlichenko Lidiya
- Papachristou Georgios I.
- Parisi Joseph E.
- Pericak-Vance Margaret A.
- Peskind Elaine
- Petersen Ronald C.
- Pierce Aimee
- Poon Wayne W.
- Potter Huntington
- Quinn Joseph F.
- Raj Ashok
- Raskind Murray
- Reiman Eric M.
- Reisberg Barry
- Reitz Christiane
- Ringman John M.
- Roberson Erik D.
- Roeder Kathryn
- Romagnuolo Joseph
- Rosen Howard J.
- Rosenberg Roger N.
- Sandhu Bimaljit S.
- Sano Mary
- Saykin Andrew J.
- Schellenberg Gerard D.
- Schneider Julie A.
- Schneider Lon S.
- Seeley William W.
- Sherman Stuart
- Simon Peter
- Singh Vijay K.
- Slivka Adam
- Smith Amanda G.
- Smith Jill P.
- Sonnen Joshua A.
- Spina Salvatore
- Stern Robert A.
- Stolz Donna
- Sutton Robert
- Tanzi Rudolph E.
- Tector Matt
- Trojanowski John Q.
- Troncoso Juan C.
- Tsuang Debby W.
- Valladares Otto
- Van Deerlin Vivianna M.
- Van Eldik Linda J.
- Vardarajan Badri N.
- Vinters Harry V.
- Vonsattel Jean Paul
- Wang Li-San
- Weintraub Sandra
- Weiss Frank Ulrich
- Welsh-Bohmer Kathleen A.
- Whitcomb David C.
- Wilcox C. Mel
- Williamson Jennifer
- Wisniewski Stephen R.
- Woltjer Randall L.
- Wright Clinton B.
- Yadav Dhiraj
- Younkin Steven G.
- Yu Chang-En
- Yu Lei
- Zarnescu Narcis Octavian
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 13/02/2014
- Field of study
Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07
The genetic architecture of the human cerebral cortex
- Author
- Adams Hieab H H
- Adams Hieab H H
- Agartz Ingrid
- Ahlijanian Michael
- Ahmad Shahzad
- Ainscough Susan
- Aisen Paul
- Albers Colleen S
- Albert Marilyn
- Alhusaini Saud
- Allard Joanne
- Almeida Marcio A A
- Alnæs Dag
- Alvim Marina K M
- Ames David
- Ames David
- Amin Najaf
- Amlien Inge K
- Amouyel Philippe
- Ances Beau
- Anderson Karen
- Anderson Tim J
- Andersson Micael
- Andreassen Ole A
- Andreassen Ole A
- Apostolova Liana
- Ard Tyler
- Arias-Vasquez Alejandro
- Armstrong Nicola J
- Armstrong Nicola J
- Arnedo Vanessa
- Arnold Steven E
- Artiges Eric
- Artiges Eric
- Ashley-Koch Allison
- Assaly Michele
- Assareh Amelia A
- Asthana Sanjay
- Atkins Joshua R
- Aydin Semiha
- Ayesa-Arriola Rosa
- Baca Marne
- Bachman David
- Banaschewski Tobias
- Barbot Alexis
- Barker Gareth
- Barone Paolo
- Bartha Rob
- Bartzokis George
- Bastin Mark E
- Bastin Mark E
- Bates Vernice
- Baune Bernhard T
- Becerra Mauricio
- Becker Andreas
- Becker James T
- Beckett Laurel
- Beckham Jean C
- Beiser Alexa S
- Belden Christine M
- Belger Aysenil
- Bell Karen L
- Berg Daniela
- Bergman Howard
- Bernard Manon
- Bernard Manon
- Bernick Charles
- Bernstein Matthew
- Beyer Frauke
- Bezivin-Frere Pauline
- Biondo Francesca
- Bis Joshua C
- Bis Joshua C
- Bishop Courtney
- Black Sandra
- Blangero John
- Blank Karen
- Bodge Courtney
- Bokde Arun
- Bonakdarpour Borna
- Boomsma Dorret I
- Borges-Neto Salvador
- Borowski Bret
- Borrie Michael
- Bralten Janita
- Brand Connie
- Brandabur Melanie
- Brandt Christine L
- Brewer James
- Brockington John
- Brodaty Henry
- Brodaty Henry
- Bromberg Uli
- Brooks David
- Brooks William M
- Brosch Jared R
- Brouwer Rachel M
- Brown Gregory G
- Bruehl Ruediger
- Brunner Han G
- Buckholtz Neil
- Buckner Randy L
- Budson Andrew E
- Buimer Elizabeth E L
- Buitelaar Jan K
- Burke Anna
- Burns Jeffrey M
- Bustillo Juan R
- Bülow Robin
- Bülow Robin
- Bürger Christian
- Bÿchel Christian
- Cabrera Yuliana
- Cahn Wiepke
- Cairns Murray J
- Cairns Nigel J
- Calhoun Vince
- Cannon Dara M
- Capote Horacio
- Carlsson Cynthia M
- Carmichael Owen
- Carr Vaughan J
- Carrillo Maria
- Carroll Maria
- Carson Richard E
- Carter Raina
- Casaceli Cynthia
- Casalin Paola
- Caseras Xavier
- Caspell Chelsea
- Caspers Svenja
- Catafau Ana
- Cavalleri Gianpiero L
- Cedarbaum Jesse
- Cellar Janet S
- Celmins Dzintra
- Cendes Fernando
- Chahine Lama
- Chakravarty Mallar
- Chalker Alison
- Chao Steven
- Chen Kewei
- Chen Qiang
- Chertkow Howard
- Cheung Joshua W
- Chiang Gloria
- Ching Christopher R K
- Chowdhury Munir
- Chowdhury Sohini
- Chu Congying
- Cichon Sven
- Clark Christopher M
- Clark David
- Coffey Christopher
- Coleman Edward
- Colodro-Conde Lucía
- Comery Thomas
- Conrad Gary
- Conrod Patricia
- Consortium CHARGE
- Consortium Enhancing NeuroImaging Genetics through Meta-Analysis
- Consortium EPIGEN
- Consortium IMAGEN
- Consortium SYS
- Correia Stephen
- Corvin Aiden
- Couvy-Duchesne Baptiste
- Crawford Karen
- Creech Mary L
- Crespo-Facorro Benedicto
- Crivello Fabrice
- Curran Joanne E
- D'Agostino Daniel
- Daedelow Laura
- Daiello Lori A
- Dale Anders M
- Dale Anders M
- Dalley Jeffrey
- Dalrymple-Alford John C
- Dalvie Shareefa
- Dang Mimi
- Dannlowski Udo
- Darin Abigail
- Davies Gareth E
- Davies Peter
- de Araujo Tânia K
- de Geus Eco J C
- de Zubicaray Greig I
- de Zwarte Sonja M C
- Deary Ian J
- Deary Ian J
- Debette Stephanie
- Debette Stephanie
- Decarli Charles
- DeCarli Charles
- Deeley Cheryl
- Degenhardt Franziska
- Delanty Norman
- DeMarco Kathryn
- den Braber Anouk
- Dennis Michelle F
- Depondt Chantal
- Desrivieres Sylvane
- Desrivières Sylvane
- Dietsche Bruno
- Djurovic Srdjan
- Doan Nhat Trung
- Doherty Colin P
- Dohm Katharina
- Dolen Sara
- Donohoe Gary
- Donohue Michael
- Doody Rachelle S
- Dooley Eoin
- Doraiswamy P Murali
- Drost Dick
- Duara Ranjan
- Dubow Jordan S
- Dunlop Becky
- Egebjerg Jan
- Ehrlich Stefan
- El Khouli Riham
- Engelbrecht Hannah-Ruth
- Erk Susanne
- Espay Alberto
- Espay Kristy
- Espeseth Thomas
- Espiritu Ryan
- Faber Kelley
- Factor Stewart
- Fan Chun Chieh
- Fargher Kristin
- Farlow Martin R
- Fatica Parianne
- Fedko Iryna O
- Feldman Howard
- Fernandez Hubert
- Fernández Guillén
- Figurski Michal
- Filippi Irina
- Fillit Howard
- Fillmer Ariane
- Finger Elizabeth
- Fisher Simon E
- Flashman Laura A
- Fleisher Adam
- Fletcher Evan
- Flor Herta
- Flor Herta
- Foley Sonya F
- Fontaine Deborah
- Fontoura Paulo
- Ford Judith M
- Fornage Myriam
- Fornage Myriam
- Foroud Tatiana
- Foroud Tatiana M
- Forstner Andreas J
- Foster Eric
- Foster Norm
- Fox Nick
- Francks Clyde
- Frank Richard
- Frank Samuel
- Franke Barbara
- Franklin Erin
- Franz Carol E
- Frasier Mark
- Frouin Vincent
- Fröhner Juliane
- Fukunaga Masaki
- Gaikwad Mrunalini
- Galasko Douglas
- Garavan Hugh
- Garijo Daniel
- Garrett Melanie E
- Gauss Katharina
- Ge Tian
- Geldmacher David
- Gessert Devon
- Ghanbari Mohsen
- Giddaluru Sudheer
- Gigliotti Christina
- Gil Yolanda
- Gillespie Nathan A
- Glahn David C
- Gloer Katherine
- Goldman Aaron L
- Goldstein Bonnie S
- Goldstein David B
- Gollub Randy L
- Gowland Penny
- Gowland Penny A
- Grabe Hans J
- Grabe Hans Jörgen
- Grachev Igor D
- Graff-Radford Neill R
- Grasby Katrina L
- Green Davis Robert C
- Green Melissa J
- Green Robert C
- Green Robert C
- Greig-Custo Maria T
- Griffith Randall
- Grimmer Yvonne
- Groenewold Nynke A
- Grossman Hillel
- Grotegerd Dominik
- Gruber Oliver
- Gudnason Vilmundur
- Gunter Jeff
- Gurholt Tiril P
- Guthrie Stephanie
- Gutman Boris A
- Hake Ann Marie
- Hansell Narelle K
- Hardy Peter
- Hariri Ahmad R
- Harlan Sherry
- Harless Kelly
- Harris Mat
- Harris Mathew A
- Harrison Marc B
- Hart David
- Hartman Catharina A
- Harvey Danielle
- Hashimoto Ryota
- Haswell Courtney C
- Hauser Michael
- Hauser Robert
- Hawkins Keith A
- Hefti Franz
- Heidebrink Judith L
- Heindel Walter
- Heinz Andreas
- Heinz Andreas
- Heinzen Erin L
- Henskens Frans A
- Hergesheimer Lindsey
- Herms Stefan
- Hernando Raymundo
- Herring Scott
- Heslenfeld Dirk J
- Hetelle Joel
- Hewitt David L
- Heyn Chris Chinthaka
- Hibar Derrek P
- Hillegers Manon H J
- Himali Jayandra J
- Ho Beng-Choon
- Ho New Fei
- Hoehn David
- Hoekstra Pieter J
- Hofer Edith
- Hofer Edith
- Hoffmann Per
- Hoffmann Wolfgang U
- Hofman Albert
- Hogarth Penelope
- Hohmann Sarah
- Holleran Laurena
- Holmes Avram J
- Holsboer Florian
- Holtzman David
- Homuth Georg
- Hong L Elliot
- Honig Lawrence S
- Hoogman Martine
- Hopkins William D
- Hosein Chris
- Hosten Norbert
- Hottenga Jouke-Jan
- Hsiao John
- Hsiung Ging-Yuek Robin
- Hu Shu-Ching
- Hulshoff Pol Hilleke E
- Hunter Christine
- Hynes Mary L
- Häusler Alexander N
- Håberg Asta K
- Ihlenfeld Albrecht
- Ikeda Masashi
- Ikram M Arfan
- Ikram M Arfan
- Ing Alex
- Initiative Alzheimer’s Disease Neuroimaging
- Initiative Parkinson’s Progression Markers
- Iranzo Alex
- Isaacson Stuart
- Isensee Corinna
- Ismail M Saleem
- Ittermann Bernd
- Jack Clifford R
- Jack Clifford R
- Jagust William
- Jahanshad Neda
- James Angela
- James Olga
- James Raymond
- Jang MiHyun
- Jankovic Joseph
- Janowitz Deborah
- Jansen Andreas
- Jansen Iris E
- Jennings Danna
- Jernigan Terry L
- Jia Tianye
- Jia Tianye
- Jian Xueqiu
- Jiang Jiyang
- Jicha Greg
- Jimenez Gustavo
- Jockwitz Christiane
- Johnson Kathleen
- Johnson Keith A
- Johnson Kris
- Johnson Nancy
- Johnson Patricia Lynn
- Johnson Sterling
- Jones David
- Jönsson Erik G
- Kahn René S
- Kanai Ryota
- Kantarci Kejal
- Karama Sherif
- Karama Sherif
- Karlawish Jason H
- Kasperaviciute Dalia
- Kass Joseph S
- Kataki Maria
- Kaufmann Tobias
- Kaye Jeffrey A
- Kelly Sinead
- Keltz Melanie
- Kennedy Martin A
- Kertesz Andrew
- Kerwin Diana
- Khachaturian Zaven
- Kieburtz Karl
- Kielb Stephanie
- Kikuchi Masataka
- Killiany Ronald
- Kim Sungeun
- Kimbrel Nathan A
- Kircher Tilo T J
- Kittur Smita
- Kiyasova Vera
- Klein Marieke
- Knapp Michael
- Knodt Annchen R
- Knol Maria J
- Knopman David
- Kochunov Peter
- Koeppe Robert A
- Koleva Hristina
- Kolskår Knut
- Koops Sanne
- Kopil Catherine
- Korecka Magdalena
- Kowalksi Nancy
- Kowall Neil
- Kremen Sarah
- Kremen William S
- Krug Axel
- Krämer Bernd
- Kuller Lew
- Kwok John B
- Kwok John B J
- Lah James J
- Lam Max
- Lamar Melissa
- Lamb Ashley
- Lancaster Thomas M
- Landau Susan
- Lane Barton
- Lasch Shirley
- Launer Lenore
- Le Hellard Stephanie
- Leach Christi
- Leary Laura
- Lee Athena
- Lee Phil H
- Lee T-Y
- Lee Virginia
- Lemaitre Hervé
- Lenahan Art
- Leonard Gabriel
- Lerner Alan
- Lethbridge Emma
- Lett Tristram A
- Leverenz James
- Levey Allan I
- Lewis Lindsay
- Lewis Lindsay B
- Li Shuo
- Liang Grace
- Lim Kelvin O
- Lin Honghuang
- Lin Michael
- Lind Betty
- Lind Penelope A
- Linder Carly
- Lipowski Kristine
- Loeffler Markus
- Logovinsky Veronika
- Logue Mark
- Longstreth W. T.
- Longstreth William T
- Lopes-Cendes Iscia
- Lopez Oscar L
- Lopez Oscar L
- Lord Joanne L
- Loughland Carmel M
- Love Marissa Natelson
- Lu Po H
- Luciano Michelle
- Luciano Michelle
- Luykx Jurjen J
- Lyons Michael J
- Macciardi Fabio
- Maillard Pauline
- Maingault Sophie
- Makino Kelly M
- Malferrari Giulia
- Malloy Paul
- Marek Kenneth
- Mari Zoltan
- Marquand Andre F
- Marshall Gad A
- Marson Daniel
- Martin Kim
- Martin Nicholas G
- Martinot Jean-Luc
- Martinot Jean-Luc
- Martinot Marie-Laure Paillère
- Mason Sara S
- Mathalon Daniel H
- Mather Karen A
- Mather Karen A
- Mathews Dana
- Mathias Samuel R
- Mathis Chet
- Mattay Venkata S
- Matthews Brandy R
- Matthews Sarah
- Mayoral Van Son Jaqueline
- Mazoyer Bernard
- Mazoyer Bernard
- McCoy Arita
- McDonald Colm
- McEwen Sarah C
- McMahon Katie L
- McMahon Mary Agnes B
- Medland Sarah E
- Melle Ingrid
- Melzer Tracy R
- Mendick Susan
- Mesulam M Marcel
- Mesulam Marek-Marsel
- Meyer Javier Villanueva
- Meyer-Lindenberg Andreas
- Michie Patricia T
- Milaneschi Yuri
- Millenet Sabina
- Miller Bruce L
- Miller Delwyn D
- Miller Sarah
- Minton Mark
- Mintun Mark A
- Mintz Akiva
- Mintzer Jacobo
- Miranda Ruben
- Mirza-Schreiber Nazanin
- Mishra Aniket
- Mitsis Effie
- Mollenhauer Brit
- Monahan Nancy
- Montine Tom
- Moreira Jose C V
- Morey Rajendra A
- Morris Derek W
- Morris John
- Morris John C
- Mosley Thomas H
- Mosley Thomas H
- Mota Nina Roth
- Mowry Bryan
- Mudge Benita
- Mueller Bryon A
- Muglia Pierandrea
- Mule Jennifer
- Muni Donna
- Mühleisen Thomas W
- Müller-Myhsok Bertram
- Najt Pablo
- Nakahara Soichiro
- Nam Ki Won
- Nauck Matthias
- Neale Michael C
- Nees Frauke
- Neu Scott
- Nho Kwangsik
- Nho Kwangsik
- Niessen Wiro J
- Norbash Alexander
- Nordvik Jan E
- Nyberg Lars
- Nöthen Markus M
- O'Leary Daniel S
- Oakley MaryAnn
- Oates Elizabeth
- Obisesan Thomas O
- Obradov Sanja
- Ogrocki Paula
- Ogunlana Olu
- Olde Loohuis Loes M
- Olichney John
- Oliver Angela
- Onyike Chiadi
- Oosterlaan Jaap
- Opel Nils
- Ophoff Roel A
- Orfanos Dimitri Papadopoulos
- Ostrowizki Suzanne
- Ott Brian R
- Ottmann Ruth
- Oyonumo Ntekim E
- Pacini Nathaniel
- Paillere Marie-Laure
- Painter Jodie N
- Panizzon Matthew S
- Pantelis Christos
- Papadopoulos Dimitri
- Parfitt Francine
- Pasternak Stephen
- Paul Steven
- Paus Tomas
- Paus Tomáš
- Pausova Zdenka
- Pausova Zdenka
- Pavese Nicola
- Pavlik Valory
- Pavlosky William
- Pawluczyk Sonia
- Pearlson Godfrey D
- Pearson John F
- Penninx Brenda W J H
- Pentilla Jani
- Perron Michel
- Perry David
- Petersen Ronald
- Petrella Jeffrey R
- Pierce Aimee
- Pike G Bruce
- Pike G Bruce
- Pirpamer Lukas
- Pitcher Toni L
- Pizzagalli Fabrizio
- Poewe Werner
- Poki-Walker Kim
- Polderman Tinca J C
- Poline Jean-Baptiste
- Pomara Nunzio
- Porsteinsson Anton P
- Portillo Alicia
- Posthuma Danielle
- Potkin Steven
- Potter William
- Poustka Luise
- Preda Adrian
- Psaty Bruce M
- Pütz Benno
- Quiceno Mary
- Quidé Yann
- Quinlan Erin B
- Quinlan Erin Burke
- Quinn Joseph
- Rachinsky Irina
- Radtke Rodney
- Ragothaman Anjanibhargavi
- Raichle Marc
- Rainka Michelle
- Raj Balebail Ashok
- Ranola Madelaine
- Rapp Michael
- Rashid Faisal M
- Rasser Paul E
- Ratnakar Varun
- Ravdin Lisa
- Ravina Bernard
- Rawlins Ashlee
- Reay William R
- Redlich Ronny
- Reeder Stephanie
- Rees Linda
- Reiman Eric M
- Reinbold Céline S
- Reith Alastair D
- Relkin Norman
- Reppermund Simone
- Repple Jonathan
- Reynolds Brigid
- Richard Geneviève
- Richard Irene
- Richer Louis
- Riedel Brandalyn C
- Rietschel Marcella
- Riordan Cheryl
- Risacher Shannon L
- Robbins Trevor
- Robert Gabriel
- Rocha Cristiane S
- Rodriguez Rosemarie
- Roffman Joshua L
- Rogalski Emily
- Rogers John
- Rosen Allyson
- Rosen Howard J
- Roshchupkin Gennady V
- Roshchupkin Gennady V
- Rotter Jerome I
- Rountree Susan
- Rowe Dominic
- Rowland Laura M
- Rudolph Alice
- Ruggeri Barbara
- Russell David
- Saba Barbara
- Saba Yasaman
- Sachdev Perminder S
- Sachdev Perminder S
- Sadowski Martin
- Sadowsky Carl
- Salazar Jennifer
- Salloway Stephen
- Salminen Lauren
- Samuels Patricia
- Santulli Robert B
- Saremi Arvin
- Sarrael Antero
- Satizabal Claudia L
- Satizabal Claudia L
- Saykin Andrew J
- Saykin Andrew J
- Schall Ulrich
- Scharre Douglas W
- Schlag Fenja
- Schmaal Lianne
- Schmidt Helena
- Schmidt Reinhold
- Schmidt Reinhold
- Schneider Lon S
- Schneider Stacy
- Schofield Peter R
- Schofield Peter R
- Scholz Markus
- Schuff Norbert
- Schultz Susan K
- Schumann Gunter
- Schumann Gunter
- Scott Rodney J
- Secolin Rodrigo
- Seibyl John
- Seiler Stephan
- Seltzer Marc
- Senjem Matt
- Seppi Klaus
- Seshadri Sudha
- Seshadri Sudha
- Shah Bina
- Shah Raj C
- Shapland Chin Yang
- Shatokhina Natalia
- Shaw Leslie M
- Sheikh Mohammed O
- Shen Li
- Shen Li
- Sherer Todd
- Shianna Kevin
- Shibley Victoria
- Shill Holly
- Shim Hyungsub
- Shin Jean
- Shumskaya Elena
- Siderowf Andrew
- Silbert Lisa C
- Silverman Daniel H S
- Silverstein Rebecca
- Sim Kang
- Simpson Donna M
- Simuni Tanya
- Singleton Andrew
- Singleton-Garvin Jamika
- Sink Kaycee M
- Sirrel Sherye A
- Sisodiya Sanjay M
- Smith Amanda
- Smith Charles D
- Smith Karen Ekstam
- Smolka Michael
- Smoller Jordan W
- Snyder Peter
- Snyder Peter J
- Soares Holly
- Sommer Iris E
- Sorensen Greg
- Sosa Elizabeth
- Sossi Vesna
- Spann Bryan M
- Sperling Reisa A
- Spicer Kenneth
- Sprenger Fabienne
- Sprooten Emma
- St Pourcain Beate
- Standaert David
- Steen Vidar M
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- Stein Dan J
- Stein Jason L
- Stern Matthew
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- Swerdlow Russell H
- Sämann Philipp G
- Sønderby Ida E
- Tanner Caroline
- Tansey Katherine E
- Tarawneh Rawan
- Tariot Pierre
- Tatsuoka Curtis
- Taylor Joy L
- Taylor Peggy
- Taylor-Reinwald Lisa
- Teng Edmond
- Teodoro Liberty
- Tetrud James
- Teumer Alexander
- Teumer Alexander
- Thai Gaby
- Thal Leon
- Thalamuthu Anbupalam
- Thalamuthu Anbupalam
- Thomas Cathi-Ann
- Thomopoulos Sophia I
- Thompson Paul
- Thompson Paul M
- Tingus Kathleen
- Tinklenberg Jared
- Todd Gretchen
- Toga Arthur
- Toga Arthur W
- Toga Arthur W
- Tolosa Eduardo
- Tooney Paul A
- Tordesillas-Gutiérrez Diana
- Torres Fábio R
- Tran Baochan
- Tremont Geoffrey
- Trncic Nadira
- Trojanowki John Q
- Trollor Julian
- Trollor Julian N
- Turner Jessica A
- Turner Raymond Scott
- Tzourio Christophe
- Uhlmann Anne
- Uitterlinden André G
- Ulysse Anaztasia
- Umek Robert
- Uribe Liz
- Vaishnavi Sanjeev
- Vallerga Costanza Ludovica
- van 't Ent Dennis
- van der Brug Marcel
- van der Lee Sven J
- van der Meer Dennis
- Van der Wee Nic J A
- van Donkelaar Marjolein M J
- van Duijn Cornelia M
- van Dyck Christopher H
- van Eijk Liza
- van Erp Theo G M
- van Haren Neeltje E M
- van Noort Betteke
- van Rooij Daan
- van Tol Marie-José
- Vanderswag Helen
- Varma Pradeep
- Veillette Suzanne
- Veldink Jan H
- Veltman Dick J
- Vemuri Prashanthi
- Venkov Heli
- Verhoef Ellen
- Vernooij Meike W
- Villena Teresa
- Villringer Arno
- Voyvodic James T
- Völker Uwe
- Völzke Henry
- Walter Henrik
- Walter Henrik
- Walter Sarah
- Walton Esther
- Wang Mingyuan
- Wang Yunpeng
- Ward Chad
- Wardlaw Joanna M
- Wardlaw Joanna M
- Weber Bernd
- Weinberger Daniel R
- Weiner Michael
- Weiner Michael W
- Weintraub Sandra
- Wen Wei
- Wen Wei
- Westlye Lars T
- Whelan Christopher D
- Whelan Robert
- Whelan Robert
- White Tonya
- Willeke Diana
- Williams Karen
- Williams Steve
- Wilson Renee
- Winkfield David
- Witbracht Megan
- Witt Stephanie H
- Witte A Veronica
- Wittfeld Katharina
- Wittfeld Katharina
- Wolf Christiane
- Wolfers Thomas
- Wolk David A
- Womack Kyle
- Wong Terence Z
- Woo Ellen
- Wright Margaret J
- Wright Margaret J
- Wu Chuang-Kuo
- Wu Jing Qin
- Wurster Isabel
- Xia Rui
- Yamamori Hidenaga
- Yanez Beatriz
- Yang Mia
- Yang Qiong
- Yang Qiong
- Yankey Jon
- Yasuda Clarissa L
- Yeh Randy
- Yesavage Jerome
- Zamrini Edward
- Zare Habil
- Zaremba Dario
- Zhang Zuo
- Zhou Juan
- Zhu Alyssa H
- Zimmerman Earl A
- Ziolkowski Jaimie
- Zsembik Leo C P
- Zwiers Marcel P
- Publication venue
- 'American Association for the Advancement of Science (AAAS)'
- Publication date
- 01/01/2020
- Field of study
The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder
Genetic mechanisms of critical illness in COVID-19.
- Author
- A A Roger Thompson
- A Abraheem
- A Agasou
- A Ahmed
- A Ali
- A Allan
- A Altabaibeh
- A Alvaro
- A Aspinwall
- A Ayers
- A Bamford
- A Barron
- A Bashyal
- A Bellini
- A Bociek
- A Botello
- A Bowes
- A Brady
- A Brayne
- A Brown
- A Brown
- A Butler
- A Campbell
- A Carter
- A Collins
- A Cowley
- A Cowton
- A Cowton
- A Cox
- A Crew
- A Dance
- A Daniel
- A Daniels
- A Dela Rosa
- A Drummond
- A Durie
- A E Heron
- A Easthope
- A Easthope
- A Evans
- A Fofano
- A Gales
- A Ganesan
- A Gardner
- A Garg
- A Gherman
- A Gordon
- A Gratrix
- A Gulati
- A Gupta
- A Haigh
- A Haldeos
- A Harrison
- A Harvey
- A Hayes
- A Higham
- A Higham
- A Hilldrith
- A Holden
- A Hormis
- A Hutcheon
- A Javaid
- A Joseph
- A Kaliappan
- A Katary
- A Kay
- A Kayani
- A Kent
- A Kirkby
- A Knight
- A Kubisz-Pudelko
- A Kuravi
- A Lewis
- A Loveridge
- A Lyle
- A Mayer
- A McAlpine
- A McCarthy
- A McGregor
- A McGregor
- A Meikle
- A Mitchell
- A Mitra
- A Morris
- A Morrison
- A Naranjo
- A Nicholson
- A Nicholson
- A Nilsson
- A Noakes
- A Patel
- A Pickard
- A Poole
- A Price
- A Puxty
- A Quinn
- A Quinn
- A Raithatha
- A Rattray
- A Reddy
- A Reed
- A Reyes
- A Rose
- A Rose
- A Rostron
- A Roy
- A Roynon-Reed
- A S Raj
- A Salberg
- A Sanderson
- A Serrano-Ruiz
- A Solesbury
- A Sukha
- A Swain
- A Tariq
- A Thomas
- A Thomas
- A Todd
- A Tomas
- A Tridente
- A Tucci
- A Turnbull
- A Uriel
- A Ustianowski
- A Vochin
- A Vuylsteke
- A Waite
- A Walden
- A Whileman
- A Wilkinson
- A Williams
- A Williams
- A Wilson
- A Zak
- A Zaki
- Achille Iolascon
- Adam Auton
- Adam Brown
- Agnese Verzuri
- Agostino Ognibene
- Agostino Riva
- Ailsa Golightly
- Alan Maclean
- Alessandra
- Alessandra Stella
- Alessandra Vergori
- Alessia Giorli
- Alexander J Mentzer
- Alice Donati
- Alison M Meynert
- Alistair Nichol
- Ana da Silva Filipe
- Andrea Antinori
- Andrea Cossarizza
- Andrea Ganna
- Andrea Tommasi
- Andrew Rambaut
- Andrew Stenhouse
- Andy Law
- Anjali J Shastri
- Anna Canaccini
- Anna Maria Pinto
- Annarita Giliberti
- Annemarie B Docherty
- Antonella D'Arminio Monforte
- Antonia Ying Wai Ho
- Antonio Di Biagio
- Antony Symons
- Arianna Emiliozzi
- Arianna Gabrieli
- Audrey Coutts
- B Anwar
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- B Baines
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- Barbara Rossetti
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- Bruno Frediani
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- Furniss James
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- Wilson James F
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- Zechner Marie
- Zhai Ranran
- Zheng Chenqing
- Publication venue
- Nature
- Publication date
- 01/01/2020
- Field of study
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Finishing the euchromatic sequence of the human genome
- Author
- . Haifeng
- . Magner
- . Yin
- Abbott Scott
- Abbott-Ozersky Amanda
- Abdellah Zahra
- Abouelleil Amr
- Abrajano Anne
- Adachi Tamami
- Adam Catherine
- Adams Charles Q.
- Adamson Aaron
- Adekoya Emmanuel
- Adio-Oduola Babajide
- Aerts Andrea
- Aggarwal Arun
- Ahmadi Alireza
- Ahmed Shahana
- Aimable Matthew
- Ainscough Rachael
- Ait-Zahra Mostafa
- Aizu Tomoyuki
- Alcivare Dana
- Alegria Michelle
- Ali Alla
- Ali Johar
- Allegria-hartmann Michelle
- Alleman Jennifer
- Allen Carlana C.
- Allen Heather
- Allen Nicole R.
- Allen Susan
- Allen Thaddeus
- Almeida Jeff
- Almond Claire
- Alsbrooks Stephen L.
- Altherr Michael R.
- Amaratunge Harshinie C.
- Ambler Andrew
- Ambrose Karen
- Ambrose Kerrie
- Amemiya Chris
- Amico-Keller Gina
- Amin Amita G.
- Anderson Mechele
- Anderson Scott
- Anderson Scott
- Andora Janice
- Andredesz Carol
- Andrew Robert
- Andrews Dan
- Andrews Daniel
- Andrews Neil
- Andrews Stephanie
- Andriese Tim
- Anthouard Véronique
- Antonarakis Stylianos E.
- Anyalebechi Vivian
- Aoki Norie
- Apostolou Sinoula
- Apweiler Eva
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- Arai Rie
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- Arellano Andre
- Arellano-Jones Perry
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- Armstrong Jon
- Arredondo Dilrukshi P.
- Arredondo Heather Hope
- Artiguenave François
- Asakawa Shuichi
- Asakawa Teruyo
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- Ashcroft Kevin
- Ashurst Jennifer
- Ashwell Robert
- Ashworth Linda K.
- Aslanidis Cara
- Asomugha Chinwe O.
- Asuncion Lawreen
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- Atkinson Andrea
- Atkinson Barry
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- Fulton Lucinda A.
- Fulton Robert S.
- Furey Terrence S.
- Furuhashi Mie
- Förste Silke
- Gabisi Abdul M.
- Gage Diane
- Gaige Tony
- Galgoczy Petra
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- Gammon Stuart
- Gao Anwu
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- Garcia Carmen
- Garcia Emilio
- Garcia Marvin
- Garcia Ricardo M, III
- Garcia-Martinez Antonio
- Gardner Alison
- Gardner Alison
- Garduno Consuelo
- Gardyna Steph
- Garner Patrick
- Garner Toni T.
- Garnes Jeffrey A.
- Garnett Jane
- Garza Melissa
- Gatewood Joseph M.
- Gatland Leigh
- Gatland Lindsay
- Gattung Stacie
- Gay Laura
- Gearin Gary
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- Gelein Cynthia
- Gelpke Maartin
- Gench Stephanie L.
- Geng Jianing
- Georgescu Anca
- Geotina Amy
- Ghori Jilur
- Ghose Sayantan
- Gibbs Ben
- Gibbs Richard A.
- Gibson Diane
- Gibson Elizabeth
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- Gong Jinying
- Gonzales Eidelyn
- Gonzalez Guillermo B.
- Gooderham April
- Goodstadt Leo
- Goodstein David
- Goodwin Lynne A.
- Gordon Catherine
- Gordon Laurie A.
- Gordon Seth
- Gorton Matthew
- Gorvad Ann
- Gould Christine
- Goyea Ernest
- Goyette Audra
- Grady Deborah I.
- Grady Michelle L.
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- Graham Joe
- Grandbois Edward
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- Grant Michael
- Grant Susan
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- Gray Bruce
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- Gray Lain
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- Griffith Jeffrey K.
- Griffiths Coline
- Griffiths Ed
- Griffiths Mark
- Griffiths-Jones Sam
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- Gu Wenyi
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- Guel Metzalli
- Guerra William
- Guevara Whitney V.
- Gui Qi
- Gunaratne Preethi
- Gunning Kate
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- Hammon Nancy
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- Hamza Khalid
- Han Guiqing
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- Hancock Julie
- Harbes Brandy A.
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- Hawes Alicia C.
- Hawkins Ebere Sylvia Onyirioha
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- Heyen Joshua
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- Hildebrand Carl E.
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- Hillyard Guy
- Hines Sandra
- Hinkins Russell
- Hinrichs Angela S.
- Hitchens Matthew Edward
- Ho Issac
- Ho Sara-Jane
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- Hodgson David
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- Hoffs Michael
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- Homsi Farah J.
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- Idlebird Devincent G.
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- Imo Kelvin C.
- Inacio Nicole
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- Ishikawa Sabine K.
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- Jia Jia
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- Krawczyk Marie-Claude
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- Kruchowski Scott S.
- Kube Michael
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- Lowenstein Michael G.
- Lowry Stephen
- Lozado Ryan J.
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- Madabhushi Ramki
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- McMurray Kimberly
- McMurray Kimberly L.
- McNinch Jenny
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- Mehta Nalini
- Meidi Patrick
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- Mercado Iracema C.
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- Nakato Eriko
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- Okumura Reina
- Okwuonu Geoffrey O.
- Okwuonu Kenneth C.
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- Olson Maynard V.
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- Patel Dina
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- Patel Ritesh
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- Perez Lesette M.
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- Zembeck Lisa
- Zeng Yixin
- Zhai Dong
- Zhan Guoping
- Zhang Bo
- Zhang Caimin
- Zhang Fengmei
- Zhang Guangyu
- Zhang Guohua
- Zhang Guohua
- Zhang Haiqing
- Zhang Haiqing
- Zhang Haiqing
- Zhang Hongbo
- Zhang Hongbo
- Zhang Jingjing
- Zhang Jingjing
- Zhang Jingkun
- Zhang Jiuchun
- Zhang Jiuchun
- Zhang Lanzhi
- Zhang Li
- Zhang Li
- Zhang Meihua
- Zhang Meng
- Zhang Ming
- Zhang Qing
- Zhang Ruhua
- Zhang Shaojie
- Zhang Tiezhen
- Zhang Wei
- Zhang Wei
- Zhang Xianglin
- Zhang Xianglin
- Zhang Xiaoliang
- Zhang Xiuqing
- Zhang Yan
- Zhang Yi
- Zhang Yilin
- Zhang Yilin
- Zhang Ying
- Zhang Yuansen
- Zhang Yuzhi
- Zhang Zhengdong
- Zhao Hongmei
- Zhao Lijian
- Zhao Shenru
- Zhao Zhijing
- Zhen Zhicheng
- Zheng Haibo
- Zhong Ming
- Zhou Carol
- Zhou Haixia
- Zhou Jianling
- Zhou Nannan
- Zhou Xinfeng
- Zhou Yan
- Zhou Yang
- Zhou Yi
- Zhu Bingying
- Zhu Bofeng
- Zhu Fenghua
- Zhu Genfeng
- Zhu Genfeng
- Zhu Miao
- Zhu Ning
- Zhu Yongge
- Zhu Zhen
- Zhuang Shitao
- Zierten Deborah
- Zimmer Andrew
- Zody Michael C.
- Zollo Massimo
- Zorrilla Sara E.
- Zuo Lin
- Publication venue
- LSU Digital Commons
- Publication date
- 21/10/2004
- Field of study
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M. S.
- Abdel-Aziz M.
- Abdelrazik M.
- Abdollahi H.
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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
Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.
- Author
- Ahmed Munaza
- Aitken Stuart
- Aitman Timothy
- Akawi Nadia
- Al Turki Saeed
- Alachkar Hana
- Ali Sonia
- Allen Hana Lango
- Allen Louise
- Allsup David
- Alvi Mohsan
- Ambegaonkar Gautum
- Ambridge Kirsty
- Anderson Carl
- Anderson Julie
- Anjum Uruj
- Anney Richard
- Antony Dinu
- Antrobus Richard
- Archer Hayley
- Armstrong Ruth
- Armstrong Ruth
- Arno Gavin
- Artigas Maria Soler
- Arumugakani Gururaj
- Ashford Sofie
- Astle William
- Attwood Antony
- Austin Steve
- Awada Jana
- Ayub Muhammad
- Bacchelli Chiara
- Bakchoul Tamam
- Balasubramaniam Senduran
- Balasubramanian Meena
- Banka Siddharth
- Baralle Diana
- Bariana Tadbir K.
- Barnicoat Angela
- Barrett Daniel M.
- Barrett Jeffrey C.
- Barrett Jeffrey C.
- Barroso Inês
- Batstone Paul
- Baty David
- Baxendale Helen
- Bayzetinova Tanya
- Beales Phil
- Bennett Chris
- Bennett David
- Bentham Jamie
- Berg Jonathan
- Bernhard Birgitta
- Bethune Claire
- Bevan A. Paul
- Bhattacharya Shoumo
- Bibi Shahnaz
- Birney Ewan
- Bitner-Glindzicz Maria
- Bitner-Glindzicz Maria
- Blackwood Douglas
- Blair Edward
- Bleda Marta
- Blyth Moira
- Bobrow Martin
- Bochukova Elena
- Boggard Harm
- Bohanna David
- Bolton Patrick
- Bolton-Maggs Paula
- Booth Claire
- Bounds Rebecca
- Bourdon Louise
- Bourn David
- Boustred Chris
- Bradley John R.
- Bradley Lisa
- Brady Angela
- Brady Angie
- Breen Gerome
- Brent Simon
- Brewer Carole
- Brown Matthew
- Browning Michael
- Brunstrom Kate
- Bryant Emily
- Bryson Christine
- Bunyan David J.
- Burn John
- Burns Siobhan
- Calissano Mattia
- Calleja Paul
- Canham Natalie
- Canham Natalie
- Carmichael Jenny
- Carss Keren
- Carss Keren
- Carss Keren J.
- Carvill Gemma L.
- Castle Bruce
- Caulfield Mark
- Chalmers Elizabeth
- Chandler Kate
- Chandra Anita
- Chatterjee Krishna
- Chatzimichali Elena
- Chen Lu
- Chinnery Patrick
- Chitre Manali
- Church Colin
- Ciampi Antonio
- Cilliers Deirdre
- Cirak Sebhattin
- Clapham Peter
- Clarke Angus
- Clasper Susan
- Clayton Stephen
- Clayton-Smith Jill
- Clayton-Smith Jill
- Clement Emma
- Clement Gail
- Clements-Brod Naomi
- Clowes Virginia
- Clowes Virginia
- Coates Andrea
- Coates Guy
- Coghlan Gerry
- Cole Trevor
- Colgiu Irina
- Collier David
- Collins Amanda
- Collins Peter
- Collinson Morag N.
- Connell Fiona
- Cooper Nichola
- Cooper Nicola
- Cosgrove Catherine
- Cox Helen
- Cox Tony
- Craddock Nick
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- Varghese Vinod
- Vasudevan Pradeep
- Veltman Marijke
- Vijayarangakannan Parthiban
- Vijayarangakannan Parthiban
- Visscher Peter M.
- Vogt Julie
- Vogt Julie
- von Ziegenweldt Julie
- Vonk Noordegraaf Anton
- Wain Louise V.
- Wakeling Emma
- Wakeling Emma
- Wallwark Sarah
- Walters James T.R.
- Wang Guangbiao
- Wang Jun
- Wang Yu
- Wanjiku Ivy
- Ward Kirsten
- Warner Timothy Q.
- Wassmer Evangeline
- Wassmer Evangeline
- Waters Jonathon
- Watkins Hugh
- Weber Astrid
- Webster Andrew
- Welch Steve
- Wellesley Diana
- Westbury Sarah
- Wharton John
- Wheeler Elanor
- Whiteford Margo
- Whitehorn Deborah
- Whyte Tamieka
- Widaa Sara
- Wilcox Sarah
- Wilkins Martin
- Wilkinson Emily
- Willcocks Lisa
- Williams Denise
- Williams Hywel
- Williams Nicola
- Williamson Catherine
- Williamson Kathleen A.
- Wilson Crispian
- Wilson Louise
- Wong Kim
- Woods Geoff
- Woods Geoffrey
- Wort John
- Wragg Christopher
- Wright Caroline F.
- Wright Michael
- Xu ChangJiang
- Yang Jian
- Yates Laura
- Yau Michael
- Yeatman Nigel
- Yong Patrick
- Young Tim
- Yu Ping
- Zhang Fend
- Zhang Pingbo
- Publication venue
- AJHG
- Publication date
- 01/01/2019
- Field of study
The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)
A novel Alzheimer disease locus located near the gene encoding tau protein
- Author
- A Boland
- A C Naj
- A David Smith
- A Hofman
- A L Destefano
- A L Fitzpatrick
- A M Goate
- A R Laza
- A R Winslow
- A Ramirez
- A V Smith
- Adam Boxer
- Aimee Pierce
- Alberto Llèo
- Alberto Pilotto
- Alexa Beiser
- Alexandra Stretton
- Alexis Brice
- Allan I Levey
- Amanda G Smith
- Amanda J Myers
- Amanda Partch
- Ammar Al-Chalabi
- Amy Gerrish
- Ana Mauleón
- Andre G Uitterlinden
- Andrew B Singleton
- Andrew J Saykin
- Andrew McQuillin
- Andrew N McDavid
- Andrew P Lieberman
- André Lacour
- Angharad Morgan
- Ann C McKee
- Anna Karydas
- Anna M Toeglhofer
- Anna Maria Töglhofer
- Annick Alpérovitch
- Anthony Bayer
- Antonia Germanou
- Antonio González-Perez
- Aoibhinn Lynch
- Ashok Raj
- B Grenier-Boley
- B M Psaty
- B W Kunkle
- Badri N Vardarajan
- Barry Reisberg
- Benedetta Nacmias
- Bernadette McGuinness
- Bernardino Ghetti
- Bradley F Boeve
- Bradley T Hyman
- Brian Lawlor
- Britta Schürmann
- Bruce L Miller
- C A Ibrahim-Verbaas
- C Bellenguez
- C Berr
- C Brayne
- C Cruchaga
- C Dufouil
- C Holmes
- C M van Duijn
- C Tzourio
- C Van Broeckhoven
- Carlos Cruchaga
- Carol A Miller
- Caroline Graff
- Chang-En Yu
- Charlene Thomas
- Charles DeCarli
- Chiao-Feng Lin
- Chris S Carlson
- Christiane Reitz
- Christine Herold
- Christine M Hulette
- Christopher E Shaw
- Christopher Medway
- Chuang-Kuo Wu
- Chuanhai Cao
- Claudia Satizabal
- Clinton B Wright
- Clinton T Baldwin
- Constantine G Lyketsos
- Craig S Atwood
- Cynthia M Carlsson
- D A Bennett
- D Beekly
- D Campion
- D Evans
- D Hannequin
- D Harold
- D Rujescu
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- Daniel C Marson
- Daniel H Geschwind
- Daniela Galimberti
- Daniilidou Makrina
- David C Rubinsztein
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- Dmitriy Drichel
- Donald R Royall
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- Douglas R Galasko
- E B Larson
- E M Reiman
- E R Martin
- Edward H Koo
- Eileen H Bigio
- Ekaterina Rogaeva
- Elaine Peskind
- Eliecer Coto
- Eliezer Masliah
- Elio Scarpini
- Elizabeth A Crocco
- Elizabeth Fisher
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- Eric Boerwinkle
- Erik D Roberson
- F Pasquier
- F Yesim Demirci
- Fernando Rivadeneira
- Florentino Sanchez Garcia
- Francesco Panza
- Francisco J Morón
- Frank Jessen
- Frank M LaFerla
- Frank Martiniuk
- G D Schellenberg
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- G Jun
- G W Beecham
- Gail P Jarvik
- Ge Li
- Gerhard Ransmayr
- Giancarlo Russo
- Gianfranco Spalletta
- Gill Livingston
- Gina Bisceglio
- Gordon Wilcock
- Gregory A Jicha
- H Hampel
- H Schmidt
- H-Erich Wichmann
- Hakon Hakonarson
- Harriet Oldham
- Harry V Vinters
- Heike Kölsch
- Helena C Chui
- Hendrik van den Bussche
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- Joan S Reisch
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- Johannes Kornhuber
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- M A Ikram
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- M A Pericak-Vance
- M Boada
- M C O'Donovan
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- M I Kamboh
- M L Dunstan
- M Lathrop
- M M Nöthen
- M Vronskaya
- Magda Tsolaki
- Maitee Rosende Roca
- Malcolm Dick
- Manuel Mayhaus
- Marc Delepine
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- Mark A Sager
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- Marsel Mesulam
- Martin Dichgans
- Martin Ingelsson
- Martin R Farlow
- Martin Rossor
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- Michelle Lupton
- Michjael M Barmada
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- Minerva M Carrasquillo
- Montserrat Alegret
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- Natalie Ryan
- Neil W Kowall
- Neill R Graff-Radford
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- O Hanon
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- Olymbia Gkatzima
- Onofre Combarros
- Oscar L Lopez
- P Amouyel
- P De Jager
- P H St George-Hyslop
- P Holmans
- P K Crane
- P Passmore
- P Pastor
- P V Jonsson
- Panagiotis Deloukas
- Paola Bossù
- Paolo Caffara
- Pascale Barberger-Gateau
- Patrick G Kehoe
- Patrizia Mecocci
- Paul Freudenberger
- Paul Hollingworth
- Per Hoffmann
- Perrie M Adams
- Peter Dal-Bianco
- Peter J Koudstaal
- Petroula Proitsi
- Philip A Wolf
- Philip L De Jager
- R Barber
- R Clarke
- R F A G de Bruijn
- R Mayeux
- R Schmidt
- R Sims
- Rachelle S Doody
- Randall L Woltjer
- Ranjan Duara
- Regina M Carney
- Reiner Heun
- Reposo Ramírez-Lorca
- Rhian Gwilliam
- Rhoda Au
- Rita Guerreiro
- Robert A Stern
- Robert C Green
- Roger L Albin
- Roger N Rosenberg
- Ronald C Petersen
- Ronald Kim
- Ronald L Hamilton
- Rudolph E Tanzi
- Ryan M Huebinger
- S G Younkin
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- S Love
- S Mead
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- Salvatore Spina
- Sandra Weintraub
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- Stephen Todd
- Steven E Arnold
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- Stuart Pickering-Brown
- Susan M McCurry
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- T J Montine
- T M Foroud
- Tamara B Harris
- Thomas Benke
- Thomas D Bird
- Thomas Feulner
- Thomas G Beach
- Thomas J Fairchild
- Thomas Lumley
- Tricia A Thornton-Wells
- V Chouraki
- V Deramecourt
- V Emilsson
- V Escott-Price
- V Gudnason
- Vernon S Pankratz
- Victoria Alvarez
- Vivianna M Van Deerlin
- W A Kukull
- W Maier
- Wayne C McCormick
- Wayne W Poon
- Wei Gu
- Wendy J Mack
- William Perry
- William T Longstreth Jr
- William W Seeley
- Y Kamatani
- Yoav Ben-Shlomo
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 17/03/2015
- Field of study
This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted
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