8 research outputs found
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M.S.
- Abdel-Aziz M.
- Abdelrazik M.
- Abdollahi H.
- Abdullah T.
- Abecasis G.R.
- Abecasis G.R.
- Abedalthagafi M.
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- Abraheem A.
- Abul-Husn N.S.
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- Trivedi B.
- Trodd D.
- Trogstad L.-I.S.
- Trotman S.
- Trotta T.
- Trower H.
- Truman N.
- Trumper E.
- Tsao P.
- Tselios C.
- Tsinaslanidis G.
- Tsuo K.
- Tucci A.
- Tuckey V.
- Tully R.
- Tumbarello M.
- Turki S.
- Turley P.
- Turnbull A.
- Turner K.
- Turner L.
- Turner P.
- Turner V.
- Turner-Bone I.
- Turney S.
- Turtle L.
- Tutton R.
- Twiss S.
- Tyl D.
- Tyler A.
- Uitterlinden A.G.
- Underwood S.J.
- Vaghi M.
- Vaida M.
- Valente S.
- Valentine J.
- Valentino F.
- van Blokland I.
- van Heel D.A.
- van Koutrik L.
- Varghese M.
- Vecchia M.
- Vedage D.
- Veerapen K.
- Venkatesh H.
- Venn L.D.
- Venturelli S.
- Vergori A.
- Verlander M.
- Verma A.
- Verma A.
- Verma S.S.
- Vertue M.
- Verula J.
- Verzuri A.
- Vigurs C.
- Villalonga J.M.
- Vincent R.
- Vincenti A.
- Virgilio E.
- Vitart V.
- Vizcaychipi M.P.
- Vochin A.
- Voide C.
- von Frenckell C.
- von Hohenstaufen K.A.
- Vonk J.M.
- Vulesevic B.
- Vuylsteke A.
- Wackett T.
- Wadams B.
- Waddington N.
- Wagstaff V.
- Wain L.V.
- Waite A.A.C.
- Wakefield P.
- Wakinshaw F.
- Waldron J.
- Walker D.
- Walker R.
- Walker S.
- Walker S.
- Walker S.
- Wall A.
- Walsh T.
- Walsh T.
- Walters R.K.
- Walton O.
- Wang B.
- Wang J.
- Wang X.
- Wanying Z.
- Ward G.
- Ward L.
- Ward M.
- Warden S.
- Warmerdam R.
- Warren D.
- Wassall H.
- Wasson C.
- Watkins C.
- Watson E.
- Watson G.
- Watson J.
- Watters M.
- Waugh V.
- Weaver J.
- Webster A.
- Webster D.
- Webster K.
- Wei S.
- Weiss S.T.
- Weldon C.H.
- Wells C.
- Welters I.D.
- Weston H.
- Whileman A.
- Whitbread J.
- White D.
- White I.
- White K.
- White M.
- White N.
- White N.
- Whiteley S.
- Whiteside J.
- Whittle H.
- Whitton C.
- Whyte C.
- Wicks S.J.
- Wilby E.
- Wilcox L.
- Wilcox R.
- Wild H.
- Wild L.
- Wild L.
- Wilding L.
- Wiles M.
- Wilkins J.
- Wilkinson A.
- Wilkinson B.
- Willer C.
- Williams A.
- Williams A.
- Williams A.
- Williams A.T.
- Williams D.
- Williams E.
- Williams F.
- Williams G.
- Williams H.
- Williams K.
- Williams M.
- Williams P.
- Williams S.
- Williams T.
- Willis C.
- Willis H.
- Wills M.
- Willson J.
- Wilson A.
- Wilson D.J.
- Wilson J.
- Wilson J.F.
- Wilson J.F.
- Winnard S.
- Winter-Goodwin B.
- Wolf-Roberts R.
- Wolford B.
- Wong J.
- Wood D.
- Wood H.-L.
- Wood S.
- Wood T.
- Woodford C.
- Woodruff M.
- Woods L.
- Woodyatt W.
- Woolley A.E.
- Worner R.
- Worsley L.
- Wray G.
- Wren L.
- Wrey Brown C.
- Wright D.
- Wright J.
- Wright M.
- Wrobel N.
- Wu Y.
- Wulandari R.
- Wyllie D.H.
- Wynter I.
- Xavier K.
- Xue X.
- Yadav A.
- Yang J.
- Yassen A.M.
- Yates B.
- Ye C.
- Yun N.
- Zainy T.
- Zak A.
- Zaki A.
- Zamikula J.
- Zanella I.
- Zborowski A.C.
- Zeberg H.
- Zechner M.
- Zechner M.
- Zguro K.
- Zhang M.
- Zhao J.H.
- Zheng C.
- Zhou W.
- Zitter L.
- Zlatopolsky M.
- Zongo O.
- Zucchi P.
- Zyndorf M.
- Zöllner S.
- Åsvold B.O.
- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 07/07/2022
- Field of study
Get PDFCritical 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
Insights on pathogenesis of type 2 diabetes from MODY genetics
- Author
- A. Gloyn
- A. Stride
- A. Stride
- A. Vella
- A.F. Reis
- A.L. Gloyn
- A.T. Hattersley
- B.L. Triggs-Raine
- C.S. Rose
- D. Altshuler
- D.A. Stoffers
- D.A. Stoffers
- D.T. Odom
- E.H. Hani
- E.R. Pearson
- E.R. Pearson
- E.R. Pearson
- F. Matschinsky
- F.K. Kavvoura
- H. Raeder
- H. Thomas
- I. Barroso
- I. Reynisdottir
- International HapMap Consortium
- J. Ek
- J. Weng
- J.C. Florez
- K. Hara
- K. Owen
- K. Silander
- K. Silver
- K. Yamagata
- K. Yamagata
- K.L. Mohlke
- K.R. Owen
- L. Hansen
- L.D. Love-Gregory
- L.L. Bonnycastle
- M. Weedon
- M.I. McCarthy
- M.M. Byrne
- M.M. Mahtani
- M.N. Weedon
- M.N. Weedon
- M.N. Weedon
- M.N. Weedon
- M.N. Weedon
- M.T. Malecki
- M.Y. Shiau
- Michael N. Weedon
- N. Babaya
- N. Vionnet
- P. Froguel
- P.M. Thomas
- R.A. Hegele
- R.A. Hegele
- S. Ellard
- S.A. Urhammer
- S.C. Elbein
- S.K. Hansen
- S.K. Hansen
- S.Y. Kristinsson
- T.M. Frayling
- Timothy M. Frayling
- W. Macfarlane
- W. Marz
- W. Winckler
- W. Winckler
- W.M. Macfarlane
- W.M. Macfarlane
- Y. Horikawa
- Y.L. Muller
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
No full textTaxonomy of the order Mononegavirales: update 2017
- Author
- Amarasinghe G.K. (Gaya K.)
- Basler C.F. (Christopher F.)
- Bavari S. (Sina)
- Beer M. (Martin)
- Bejerman N. (Nicolás)
- Blasdell K.R. (Kim R.)
- Bochnowski A. (Alisa)
- Briese T. (Thomas)
- Bukreyev A. (Alexander)
- Bào Y. (Yīmíng)
- Calisher C.H. (Charles H.)
- Chandran K. (Kartik)
- Collins P.L. (Peter L.)
- Dietzgen R.G. (Ralf G.)
- Dolnik O. (Olga)
- Dye J.M. (John M.)
- Dürrwald R. (Ralf)
- Easton A.J. (Andrew J.)
- Ebihara H. (Hideki)
- Fang Q. (Qi)
- Formenty P. (Pierre)
- Fouchier R.A.M. (Ron)
- Ghedin E. (Elodie)
- Harding R.M. (Robert M.)
- Hewson R. (Roger)
- Higgins C.M. (Colleen M.)
- Hong J. (Jian)
- Horie M. (Masayuki)
- James A.P. (Anthony P.)
- Jiāng D. (Dàohóng)
- Kobinger G.P. (Gary P.)
- Kondo H. (Hideki)
- Kuhn J.H. (Jens H.)
- Kurath G. (Gael)
- Lamb R.A. (Robert A.)
- Lee B. (Benhur)
- Leroy E.M. (Eric M.)
- Li M. (Ming)
- Maisner A. (Andrea)
- Mühlberger E. (Elke)
- Netesov S.V. (Sergey V.)
- Nowotny N.
- Patterson J.L. (Jean L.)
- Paweska J.T. (Janusz T.)
- Payne S.L. (Susan L.)
- Pearson M.N. (Michael N.)
- Randall R.E. (Rick E.)
- Revill P.A. (Peter A.)
- Rima B.K. (Bertus K.)
- Rota P.A. (Paul)
- Rubbenstroth D. (Dennis)
- Schwemmle M. (Martin)
- Smither S.J. (Sophie J.)
- Song Q. (Qisheng)
- Stone D.M. (David M.)
- Takada A. (Ayato)
- Terregino C. (Calogero)
- Tesh R.B. (Robert B.)
- Tomonaga K. (Keizo)
- Tordo N. (Noël)
- Towner J.S. (Jonathan S.)
- Vasilakis N. (Nikos)
- Volchkov V.E. (Viktor E.)
- Wahl-Jensen V. (Victoria)
- Walker P.J. (Peter J.)
- Wang B. (Beibei)
- Wang D. (David)
- Wang F. (Fei)
- Wang L.-F. (Lin-Fa)
- Werren J.H. (John H.)
- Whitfield A.E. (Anna E.)
- Yan Z. (Zhichao)
- Ye G. (Gongyin)
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 07/04/2017
- Field of study
No full textIn 2017, the order Mononegavirales was expanded by the inclusion of a total of 69 novel species. Five new rhabdovirus genera and one new nyamivirus genus were established to harbor 41 of these species, whereas the remaining new species were assigned to already established genera. Furthermore, non-Latinized binomial species names replaced all paramyxovirus and pneumovirus species names, thereby accomplishing application of binomial species names throughout the entire order. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV)
Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals
- Author
- Abecasis G.R. (Goncalo R.)
- Abecasis G.R. (Goncalo R.)
- Abecasis G.R. (Gonçalo R.)
- Abecasis G.R. (Gonçalo)
- Adair L.S. (Linda)
- Allison M.A. (Matthew)
- Altshuler D. (David)
- Altshuler D. (David)
- Amin N. (Najaf)
- An P. (Ping)
- Ardlie K.G. (Kristin)
- Ardlie K.G. (Kristin)
- Ariyurek Y. (Yavuz)
- Aulchenko Y.S. (Yurii S.)
- Aulchenko Y.S. (Yurii S.)
- Aulchenko Y.S. (Yurii)
- Bacquer O.L. (Olivier)
- Balkau B. (Beverley)
- Balkau B. (Beverley)
- Ballantyne C. (Christie)
- Ballantyne C.M. (Christie M.)
- Ballantyne C.M. (Christie M.)
- Bandinelli S. (Stefania)
- Bandinelli S. (Stefania)
- Barbalic M. (maja)
- Barroso I.
- Barroso I.E. (Inês)
- Barroso I.E. (Inês)
- Barter P. (Phil)
- Beekman M. (Marian)
- Beilby J.P. (John)
- Ben-Shlomo Y.
- Benediktsson R. (Rafn)
- Benediktsson R. (Rafn)
- Bennett A.J. (Amanda)
- Bennett A.J. (Amanda)
- Bergman R.N. (Richard N.)
- Bergman R.N. (Richard N.)
- Bergman R.N. (Richard N.)
- Bergmann S.M. (Sven)
- Bidulescu A. (Aurelian)
- Bis J.C. (Joshua)
- Blagieva R. (Roza)
- Bochud M. (Murielle)
- Boehm B.O. (Bernhard)
- Boehnke M. (Michael)
- Boehnke M. (Michael)
- Boehnke M. (Michael)
- Boekholdt S.M. (Matthijs)
- Boerwinkle E. (Eric)
- Boerwinkle E. (Eric)
- Boerwinkle E.A. (Eric)
- Bonnefond A. (Amélie)
- Bonnycastle L.L. (Lori L.)
- Bonnycastle L.L. (Lori L.)
- Bonnycastle L.L. (Lori)
- Boomsma D.I. (Dorret I)
- Boomsma D.I. (Dorret I.)
- Boomsma D.I. (Dorret)
- Borch-Johnsen K.
- Borecki I.B. (Ingrid B)
- Borja J.B. (Judith)
- Boström K.B. (Kristina Bengtsson)
- Bouatia-Naji N. (Nabila)
- Bravenboer B. (Bert)
- Brunner E. (Eric)
- Buchanan T.A. (Thomas)
- Bumpstead S. (Suzannah)
- Bumpstead S. (Suzannah)
- Burtt N.P. (Noël P.)
- Burtt N.P. (Noël)
- Buxbaum S.G. (Sarah)
- Böhringer S. (Stefan)
- Böttcher Y. (Yvonne)
- Campbell H. (Harry)
- Campbell H. (Harry)
- Campbell H. (Harry)
- Cao A. (Antonio)
- Carlson O.D. (Olga)
- Cauchi S. (Stephane)
- Caulfield M. (Mark)
- Caulfield M.J. (Mark J.)
- Cavalcanti-Proença C. (Christine)
- Chambers J. (John)
- Chambers J.C. (John C.)
- Charpentier G. (Guillaume)
- Charpentier G. (Guillaume)
- Chasman D.I. (Daniel)
- Chen I. (Ida)
- Chen Y.-D.I. (Yii-Der Ida)
- Chen Y.D.I. (Yii-Der Ida)
- Chines P.S. (Peter S.)
- Chines P.S. (Peter)
- Cho Y.S. (Yoon Shin)
- Clarke R. (Robert)
- Coassin S. (Stefan)
- Coin L. (Lachlan)
- Collins F.S. (Francis S.)
- Collins F.S. (Francis S.)
- Collins F.S. (Francis)
- Cooper C. (Charles)
- Cooper C. (Cyrus)
- Cooper M.N. (Matthew)
- Cornelis M. (Marilyn)
- Cornelis M. (Marilyn)
- Couper D.J. (David J.)
- Couper D.J. (David)
- Crawford G. (Gabe)
- Crawford G. (Gabe)
- Crawford G. (Gabriel)
- Crisponi L. (Laura)
- Croteau-Chonka D.C. (Damien)
- Daly M.J. (Mark)
- Dam R.M. (Rob) van
- Dastani Z. (Zari)
- Day I.N.M. (Ian)
- Dedoussis G.V. (George)
- Dehghan A. (Abbas)
- Deloukas P. (Panagiotis)
- Deloukas P. (Panagiotis)
- Delplanque J. (Jerome)
- DIAGRAM+ Consortium
- Dina C. (Christian)
- Dina C. (Christian)
- Dominiczak A. (Anna)
- Dominiczak A.F. (Anna F.)
- Doney A.S.F. (Alex S. F.)
- Doney A.S.F. (Alex)
- Duijn C.M. (Cornelia) van
- Duncan B.B. (Bruce)
- Dupuis J. (Josée)
- Dupuis J. (Josée)
- Dupuis J. (Josée)
- Döring A. (Angela)
- Ebrahim S. (Shanil)
- Egan J.M. (Josephine)
- Egan J.M. (Josephine)
- Ejebe K.G. (Kenechi)
- Elliott A.L. (Amanda)
- Elliott A.L. (Amanda)
- Elliott K.S. (Katherine)
- Elliott P. (Paul)
- Erdmann J. (Jeanette)
- Erdmann J. (Jeanette)
- Erdos M.R. (Michael)
- Erdos M.R. (Michael)
- Evans D.M. (David)
- Faire U. (Ulf) de
- Fedson A.C. (Annette)
- Feitosa M.F. (Mary Furlan)
- Ferreira T. (Teresa)
- Ferrucci L. (Luigi)
- Ferrucci L. (Luigi)
- Fischer-Rosinsky A. (Antje)
- Florez J.C. (Jose C.)
- Florez J.C. (Jose)
- Florez J.C. (Jose)
- Forouhi N.G. (Nita)
- Fouchier S.W. (Sigrid)
- Fox C.S. (Caroline)
- Fox C.S. (Caroline)
- Franklin C.S. (Christopher)
- Franklin C.S. (Christopher)
- Franks P.W. (Paul)
- Frants R. (Rune)
- Frants R.R. (Rune)
- Franzosi M.
- Frayling T.M. (Timothy M.)
- Frayling T.M. (Timothy M.)
- Frayling T.M. (Timothy M.)
- Frayling T.M. (Timothy)
- Froguel P. (Philippe)
- Froguel P. (Philippe)
- Fuchsberger C. (Christian)
- Gabriel S.B. (Stacey)
- Galan P. (Pilar)
- Ganser M. (Martha)
- Garcia M.E. (M.)
- Geus E.J.C. (Eco) de
- Gieger C. (Christian)
- Gieger C. (Christian)
- Gieger C. (Christian)
- Gieger C. (Christian)
- Glazer N.L. (Nicole)
- GLGC Investigators
- Gloyn A.L. (Anna L.)
- Gloyn A.L. (Anna)
- Go M.J. (Min Jin)
- Goel A. (Anuj)
- Gonzalez E. (Elena)
- Goodarzi M. (Mark)
- Graessler J. (Jürgen)
- Grallert H. (Harald)
- Grallert H. (Harald)
- Grarup N. (Niels)
- Grarup N. (Niels)
- Green T. (Todd)
- Greenwood C.M.T. (Celia)
- Griffin S. (Simon)
- Grimsby J. (Jonna)
- Groop L. (Leif)
- Groop L. (Leif)
- Groop L. (Leif)
- Groves C.J. (Christopher)
- Groves C.J. (Christopher)
- Grundy S.M. (Scott)
- Gudnason V. (Vilmundur)
- Guiducci C. (Candace)
- Guiducci C. (Candace)
- Guo X. (Xiuqing)
- Guo X. (Xiuqing)
- Gwilliam R. (Rhian)
- Gyllensten U. (Ulf)
- Gyllensten U. (Ulf)
- Gyllensten U. (Ulf)
- Hadjadj S. (Samy)
- Hadjadj S. (Samy)
- Haeften T.W. (Timon) van
- Hagen K. (Knut)
- Hall A.S. (Alistair)
- Hallmans G. (Göran)
- Hammond N. (Naomi)
- Hamsten A. (Anders)
- Han X. (Xijing)
- Hansen T. (Torben)
- Haritunians T. (Talin)
- Harris T.B. (Tamara B.)
- Harris T.B. (Tamara)
- Hartikainen A.L.
- Hassanali N. (Neelam)
- Hassanali N. (Neelam)
- Hastie N. (Nick)
- Hattersley A.T. (Andrew)
- Haun M. (Margot)
- Havulinna A.S. (Aki)
- Hayward C.
- Hayward C. (Caroline)
- Heath S.C. (Simon)
- Heemst D. (Diana) van
- Hegele R.A. (Robert)
- Heid I.M. (Iris)
- Heid I.M. (Iris)
- Hengstenberg C. (Christian)
- Henneman P. (Peter)
- Henneman P. (Peter)
- Hercberg S. (Serge)
- Herder C. (Christian)
- Herder C. (Christian)
- Herpt T.W. (Thijs) van
- Hicks A.A. (Andrew A.)
- Hicks A.A. (Andrew)
- Hide W.A. (Winston)
- Hillman D.R. (David)
- Hingorani A. (Aroon)
- Hitman G.A. (Graham)
- Hivert M.-F. (Marie-France)
- Hoek M. (Mandy) van
- Hofman A.
- Hofman A. (Albert)
- Hofman A. (Albert)
- Hofman A. (Albert)
- Hofmann O.M. (Oliver)
- Holm H. (Hilma)
- Hottenga J.J. (Jouke Jan)
- Hottenga J.J. (Jouke Jan)
- Hovingh G.K. (Kees)
- Hu F.B. (Frank B)
- Hu F.B. (Frank B.)
- Hu F.B. (Frank)
- Hui J. (Jennie)
- Hung J. (Joe)
- Hunter D.J. (David)
- Huth C. (Cornelia)
- Hveem K. (Kristian)
- Igl W. (Wilmar)
- Illig T. (Thomas)
- Illig T. (Thomas)
- Ingelsson E. (Erik)
- Ingelsson E. (Erik)
- Ingelsson E. (Erik)
- Isaacs A. (Aaron)
- Isaacs A.J. (Aaron)
- Isomaa B. (Bo)
- Isomaa B. (Bo)
- Jackson A.U. (Anne)
- Jackson A.U. (Anne)
- Jarvelin M.-R. (Marjo-Riitta)
- Jarvelin M.-R. (Marjo-Riitta)
- Jarvelin M.-R. (Marjo-Riitta)
- Johansen C.T. (Christopher)
- Johansson A. (Åsa)
- Johnson P.R.V. (Paul R. V.)
- Johnson P.R.V. (Paul)
- Johnson T. (Toby)
- Johnson T. (Toby)
- Johnson T. (Toby)
- Jorgensen T. (Torben)
- Jorgensen T. (Torben)
- Jula A. (Antti)
- Jula A. (Antti)
- Kaakinen M. (Marika)
- Kanaya A. (Alka)
- Kanoni S. (Stavroula)
- Kanoni S. (Stavroula)
- Kao W.H.L. (W. H. Linda)
- Kao W.H.L. (Wen H. L.)
- Kao W.H.L. (Wen)
- Kao W.H.L. (Wen)
- Kaplan L. (Lee)
- Kaprio J. (Jaakko)
- Kapur K. (Karen)
- Karpe F. (Fredrik)
- Kastelein J.J.P. (John)
- Katsareli E. (Efi)
- Kedenko L. (Lyudmyla)
- Kesaniemi Y.A. (Antero)
- Khaw K.-T. (Kay-Tee)
- Khaw K.T.
- Kim Y-J. (Yong-Jin)
- Kim Y.J.
- Kivimaki M. (Mika)
- Kizer J.R. (Jorge)
- Klopp N. (Norman)
- Klopp N. (Norman)
- Kloppenburg M. (Margreet)
- Knight B. (Beatrice)
- Kong A. (Augustine)
- Kong A. (Augustine)
- Kooner J. (Jaspal)
- Koseki M. (Masahiro)
- Koskinen S. (Seppo)
- Kovacs P. (Peter)
- Kraft P. (Peter)
- Kristiansson K. (Kati)
- Kronenberg F. (Florian)
- Kronenberg F. (Florian)
- Kumari M. (Meena)
- Kuusisto J. (Johanna)
- Kuzawa C.W. (Christopher W.)
- Kuzawa C.W. (Christopher)
- Kyvik K.O. (Kirsten O.)
- Kyvik K.O. (Kirsten Ohm)
- Kähönen M. (Mika)
- König I.R. (Inke)
- Laakso M. (Markku)
- Laakso M. (Markku)
- Laakso M. (Markku)
- Laaksonen R. (Reijo)
- Ladouceur M. (Martin)
- Lajunen T. (Taina)
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- Lange L.A. (Leslie)
- Lange L.A. (Leslie)
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- Langenberg C. (Claudia)
- Langenberg C. (Claudia)
- Langenberg C. (Claudia)
- Lathrop G. (GMark)
- Launer L.J. (Lenore J.)
- Lauritzen T. (Torsten)
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- Lecoeur C. (Cécile)
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- Lehtimäki T. (Terho)
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- Li M. (Man)
- Li M. (Man)
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- Lohman K. (Kurt)
- Lokki M.L.
- Loo B.-M. (Britt-Marie)
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- Lucas G. (Gavin)
- Lyssenko V. (Valeriya)
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- Lyytikäinen L.-P. (Leo-Pekka)
- MAGIC Consortium
- Magnusson P.K. (Patrik)
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- Voight B.F. (Benjamin F.)
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- Vollenweider P. (Peter)
- Vollenweider P. (Peter)
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- Willemsen G.
- Willemsen G.A.H.M. (Gonneke)
- Willer C.J. (Cristen J.)
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- Williams G.H. (Gordon)
- Wilson J.F. (James F.)
- Wilson J.F. (James)
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- Witteman J. (Jacqueline)
- Witteman J.C.M. (Jacqueline C. M.)
- Witteman J.C.M. (Jacqueline)
- Witteman J.C.M. (Jaqueline C. M.)
- Wong T.Y. (Tien Y.)
- Wood A.R. (Andrew)
- Wright A.F. (Alan)
- Wright A.F. (Alan)
- Wu G. (Guanming)
- Wu Y. (Ying)
- Yarnell J.W.G. (John W.)
- Yuan X. (Xin)
- Zabena C. (Carina)
- Zee R.Y.L. (Robert)
- Zeggini E. (Eleftheria)
- Zeggini E. (Eleftheria)
- Zelenika D. (Diana)
- Zethelius B. (Björn)
- Zhai G. (Guangju)
- Zhang W. (Weihua)
- Zhao J.H. (Jing Hua)
- Zhao J.H. (Jing Hua)
- Zhao J.H. (Jing Hua)
- Ziegler A. (Andreas)
- Zillikens M.C. (Carola)
- Zwart J-A. (John-Anker)
- Ódonnell C.J. (Christopher)
- Publication venue
- Publication date
- 01/01/2012
- Field of study
Get PDFCirculating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8- 1.2 ×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10−4). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10−3, n = 22,044), increased triglycerides (p = 2.6×10−14, n = 93,440), increased waist-to-hip ratio (p = 1.8×10−5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10−3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL- cholesterol concentrations (p = 4.5×10−13, n = 96,748) and decreased BMI (p = 1.4×10−4, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance
Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index
- Author
- Adamo P. (Pio) d'
- Adan R. (R.)
- Alavere H. (Helene)
- Albrecht E. (Eva)
- Alexander G. (Graeme)
- Alfredsson L. (Lars)
- Amin N. (Najaf)
- Amin N. (Najaf)
- Anderson C.A. (Carl A)
- Ando T. (Tetsuya)
- Ang W.Q. (Wei)
- Antel J. (J.)
- Aspelund T. (T.)
- Aspelund T. (Thor)
- Atalay M. (Mustafa)
- Baker J.H. (Jessica H)
- Barrett J.C. (Jeffrey)
- Barroso I.E. (Inês)
- Beijsterveldt C.E.M. (Toos) van
- Bencko V. (Vladimir)
- Benke K. (K.)
- Berenson G. (Gerald)
- Bergen A.W. (Andrew)
- Bergen N. (N.)
- Bergmann S.M. (Sven)
- Berrettini W. (Wade)
- Berry D. (Diane)
- Bierut L.J. (L. J.)
- Bierut L.J. (Laura)
- Blackburn H. (Hannah)
- Boerwinkle E. (E.)
- Boerwinkle E.A. (Eric)
- Boni C. (Claudette)
- Boomsma D.I. (Dorret)
- Boraska Perica V. (V.)
- Boyd H.A. (H. A.)
- Bradfield J.P. (Jonathan)
- Brandys M. (M.)
- Breen G. (Gerome)
- Breen G. (Gerome)
- Bruson A. (Alice)
- Bulik C.M. (C. M.)
- Burghardt R. (Roland)
- Buring J.E. (Julie)
- Busonero F.
- Busonero F. (F.)
- Byrne E.M. (E. M.)
- Byrne E.M. (Enda)
- Bühren K. (Katharina)
- Carlberg L. (Laura)
- Chanock S.J. (S. J.)
- Chanock S.J. (Stephen)
- Charoen P. (Pimphen)
- Chasman D.I. (Daniel)
- Cichon S. (Sven)
- Clementi M. (Maurizio)
- Cohen-Woods S. (Sarah)
- Coin L. (Lachlan)
- Collier D.A. (David)
- Cone R.D. (Roger D)
- Conlon P. (Peter)
- Conlon P.J. (Peter J)
- Cooper C. (C.)
- Cooper C. (Charles)
- Cornelis M. (Marilyn)
- Corre T. (Tanguy)
- Couper D.J. (David)
- Cousminer D.L. (Diana)
- Coviello A.D. (Andrea)
- Crawford S. (Steve)
- Crisponi L. (Laura)
- Crow S. (Scott)
- Danner U.N. (Unna N)
- Das S. (Shikta)
- Davey Smith G. (G.)
- Davis O.S.P. (Oliver S.)
- de Geus E.J. (E. J.)
- de Kove C. (Carolien)
- De Zwaan M. (M.)
- Dedoussis G.V. (G. V.)
- Dedoussis G.V. (George)
- Degortes D. (Daniela)
- Deloukas P. (Panagiotis)
- Demerath E.W. (E. W.)
- Demerath E.W. (Ellen)
- DeSocio J.E. (Janiece E)
- Dick D.M. (Danielle)
- Dmitrzak-Weglarz M. (Monika)
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- Dominiczak A. (Anna)
- Duijn C.M. (Cornelia) van
- Duncanson A. (Audrey)
- Döring A. (Angela)
- Econs M.J. (M. J.)
- Econs M.J. (Michael)
- Edkins T. (Ted)
- Egberts K. (Karin)
- Ehrlich S.M. (Stefan)
- Eiriksdottir G. (Gudny)
- Elburg A.A. (Annemarie) van
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- Elliott P. (P.)
- Elliott P. (Paul)
- Esko T. (T.)
- Esko T. (Tõnu)
- Espeseth T. (Thomas)
- Estivill X. (Xavier)
- Evans D.M. (D. M.)
- Faire U. (Ulf) de
- Farmer A.E. (Anne E)
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- Feenstra B. (Bjarke)
- Fernández-Aranda F. (Fernando)
- Ferreli L. (Liana)
- Ferrucci L. (L.)
- Fichter M.M. (M. M.)
- Finan C. (Chris)
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- Floyd J. (Jamie)
- Folsom A.R. (A. R.)
- Folsom A.R. (Aaron)
- Foretova L. (Lenka)
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- Franceschini N. (Nora)
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- Gillman M.W. (Matthew W.)
- Goh L.K. (L. K.)
- Gonidakis F. (Fragiskos)
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- Grant S.F.A. (S. F.A.)
- Grant S.F.A. (Struan)
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- Hattersley A.T. (Andrew)
- Hauser J. (J.)
- Haworth C.M.A. (Claire M.)
- Hayward C. (Caroline)
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- Helder S. (Sietske)
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- Herpertz-Dahlmann B. (B.)
- Herzog W. (W.)
- Hilliard C.E. (Christopher E)
- Hinney A. (Anke)
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- Warrington N.M. (Nicole)
- Waterworth D. (Dawn)
- Weedon M.N. (Michael)
- White S.J. (Stefan)
- Whittaker P. (Pamela)
- Wichmann H.E. (Heinz Erich)
- Widen E.
- Widen E. (E.)
- Willemsen G.A.H.M. (Gonneke)
- Wilson J.F. (J. F.)
- Wingerden S. (Sophie) van
- Winkler T.W. (Thomas W.)
- Woodside D.B. (D Blake)
- Wright A.F. (Alan)
- Yaghootkar H. (H.)
- Yilmaz Z. (Zeynep)
- Young L. (L.)
- Zeggini E. (Eleftheria)
- Zerwas S. (Stephanie)
- Zgaga L. (L.)
- Zhai G. (G.)
- Zhao J.H. (J. H.)
- Zhuang W.V. (W. V.)
- Zipfel S. (S.)
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/02/2017
- Field of study
No full textThe maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation
DNA and Double-Stranded Oligonucleotides
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- A. Adhikary
- A. Adhikary
- A. Adhikary
- A. Barbouti
- A. Cahill
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2006
- Field of study
No full textWhole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar Mohamed S.
- Abdel-Aziz Mahmoud
- Abdelrazik Marwa
- Abdollahi Hamed
- Abdullah T.
- Abecasis Goncalo
- Abedalthagafi M.
- Abel Lynn
- Abernathy C.
- Abraheem Azmeralde
- Abul-Husn Noura S.
- Acquilini D.
- Adams C.
- Adams Emma L.
- Adams K.
- Adamsara Alireza
- Adanini Olurenke
- Adeleye O.
- Adra D.
- Afilalo J.
- Afilalo M.
- Afolabi D.
- Afrasiabi Z.
- Agasou A.
- Agrawal Shruti
- Agüero D.
- Ahmad N.
- Ahmadi Saeideh
- Ahmed A.
- Ahmed Cecilia
- Akeroyd L.
- Akhtar M.N.
- Akinkugbe O.
- Aksentijevich Alexandra
- Al-Afghani H.
- Al-Awdah L.
- Alaamery M.
- Alahmadey Z.Z.
- Alaverdian D.
- Alavere H.
- Albader A.
- Albaiceta G.M.
- Albakri J.K.
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- Ali Altaf
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- Åsvold Bjørn Olav
- Publication venue
- Publication date
- 01/01/2022
- Field of study
No full textAltres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization 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
