16 research outputs found
Bladder-cancer-associated mutations in RXRA activate peroxisome proliferator-activated receptors to drive urothelial proliferation
- Author
- Publication venue
- Digital Commons@Becker
- Publication date
- 01/01/2017
- Field of study
Plasma Dynamics
- Author
- Bekefi George
- Bers Abraham
- Brewer Warren K.
- Bromberg Leslie
- Chrisman Paul W., Jr.
- Chu Flora Y. F.
- Cook Donald L.
- Coppi Bruno
- Dupree Thomas H.
- Ehst David A.
- Fisch Nathaniel J.
- Fisher Alan S.
- Fisher Jay L.
- Forbes Alan R.
- Freeman Richard R.
- Gottlieb Mark
- Hershcovitch Ady
- Hunter Kevin
- Johnston George L.
- Kaplan David L.
- Karney Charles F. F.
- Kaup David J.
- Kenyon Peter T.
- Kulp John L., Jr.
- Laskey Kenneth J.
- Lidsky Lawrence M.
- Maby Edward W.
- McCune James E.
- McKinstry Mark L.
- Orzechowski Thaddeus J.
- Overskei David O.
- Pant Aniket
- Pasquarelli Louis R.
- Politzer Peter A.
- Reiman Allan H.
- Reitman Allan H.
- Richards Burton
- Smullin Louis D.
- Stone David S.
- Tekula Miloslav S.
- Tetrault David J.
- Thomas Clarence E.
- Throop Alan E.
- Publication venue
- Research Laboratory of Electronics (RLE) at the Massachusetts Institute of Technology (MIT)
- Publication date
- 01/01/1976
- Field of study
Contains research objectives and summary of research on twenty-one projects split into three sections, with four sub-sections in the second section and reports on twelve research projects.National Science Foundation (Grant ENG75-06242)U.S. Energy Research and Development Administration (Contract E(11-1)-2766)U.S. Energy Research and Development Agency (Contract E(11-1)-3070)U.S. Energy Research and Development Administration (Contract E(11-1)-3070)Research Laboratory of Electronics, M.I.T. Industrial Fellowshi
Phylo: A Citizen Science Approach for Improving Multiple Sequence Alignment
- Author
- A Löytynoja
- A Löytynoja
- A Siepel
- AB Diallo
- AJ Westphal
- Alexander Kawrykow
- Alfred Kam
- AM Waterhouse
- B Knudsen
- B Paten
- BN Chorley
- C Notredame
- Chu Wu
- Clarence Leung
- D Sankoff
- Daniel Kwak
- E Korpela
- Eleyine Zarour
- F Khatib
- Gary Roumanis
- GG Loots
- J Amberger
- JS Pedersen
- Jérôme Waldispühl
- K Land
- K Lindblad-Toh
- L Chindelevitch
- L von Ahn
- L von Ahn
- L Wang
- Luis Sarmenta
- M Blanchette
- M Blanchette
- M Blanchette
- M Brudno
- M Gouy
- M Kellis
- M Shirts
- Mathieu Blanchette
- N Bray
- PA Fujita
- Pawel Michalak
- PC Ng
- S Cooper
- S De
- S Schwartz
- SB Needleman
- T Jiang
- W Fletcher
- W Miller
- WM Fitch
- Publication venue
- Public Library of Science
- Publication date
- 07/03/2012
- Field of study
BACKGROUND: Comparative genomics, or the study of the relationships of genome structure and function across different species, offers a powerful tool for studying evolution, annotating genomes, and understanding the causes of various genetic disorders. However, aligning multiple sequences of DNA, an essential intermediate step for most types of analyses, is a difficult computational task. In parallel, citizen science, an approach that takes advantage of the fact that the human brain is exquisitely tuned to solving specific types of problems, is becoming increasingly popular. There, instances of hard computational problems are dispatched to a crowd of non-expert human game players and solutions are sent back to a central server. METHODOLOGY/PRINCIPAL FINDINGS: We introduce Phylo, a human-based computing framework applying "crowd sourcing" techniques to solve the Multiple Sequence Alignment (MSA) problem. The key idea of Phylo is to convert the MSA problem into a casual game that can be played by ordinary web users with a minimal prior knowledge of the biological context. We applied this strategy to improve the alignment of the promoters of disease-related genes from up to 44 vertebrate species. Since the launch in November 2010, we received more than 350,000 solutions submitted from more than 12,000 registered users. Our results show that solutions submitted contributed to improving the accuracy of up to 70% of the alignment blocks considered. CONCLUSIONS/SIGNIFICANCE: We demonstrate that, combined with classical algorithms, crowd computing techniques can be successfully used to help improving the accuracy of MSA. More importantly, we show that an NP-hard computational problem can be embedded in casual game that can be easily played by people without significant scientific training. This suggests that citizen science approaches can be used to exploit the billions of "human-brain peta-flops" of computation that are spent every day playing games. Phylo is available at: http://phylo.cs.mcgill.ca
A Study of Gases in Porcelain Enameling
- Author
- Anson Hayes
- Badger A. E.
- Bastress A. W.
- Becker A.
- Chu P. K.
- Clarence Hahner
- Dalton R. H.
- Darken L. S.
- Davis H. M.
- Deringer W. A.
- Deringer W. A.
- Dietzel A.
- Ebright H. E.
- Enss J.
- Fanderlik M.
- Freeman S. F.
- Green R. L.
- Gruver R. M.
- Higgins W. W.
- Hoff H.
- Kautz K.
- Keeler J. H.
- Keeler J. H.
- King B. W.
- Lucian A. N.
- Marboe E. C.
- Ryde J. W.
- Salmang H.
- Shadduck H. A.
- Spencer-Strong G. H.
- Terry G. E.
- Washburn E. W.
- Weyl W. A.
- Zapffe C. A.
- Publication venue
- 'Wiley'
- Publication date
- Field of study
Effects of particle size of mono-disperse granular flows impacting a rigid barrier
- Author
- A Leonardi
- B Leroy
- B Zanuttigh
- C Berger
- CE Choi
- CE Choi
- CE Choi
- CE Choi
- CE Choi
- Charles W. W. Ng
- Clarence E. Choi
- CWW Ng
- CWW Ng
- CWW Ng
- CWW Ng
- CWW Ng
- D Mancarella
- D Proske
- D Salciarini
- D Song
- DF VanDine
- DG Lin
- DJ White
- DO Potyondy
- DP Kanungo
- F Podczeck
- GGD Zhou
- H Teufelsbauer
- H Teufelsbauer
- J DeBruyn
- JA Fleischmann
- JHS Kwan
- JMNT Gray
- JW Zhou
- JW Zhou
- K Hu
- L Bugnion
- Luis H. D. Liu
- M Brunet
- M Hürlimann
- M Jakob
- O Hungr
- O Hungr
- O Hungr
- R Brighenti
- R Valentino
- R Yuan
- R Yuan
- RCH Koo
- RM Iverson
- RM Iverson
- RM Iverson
- RPH Law
- S Hauksson
- S Moriguchi
- S Zhang
- SB Savage
- SB Savage
- SB Tan
- SP Pudasaini
- T Chu
- T Faug
- W Ashwood
- X Li
- Y Cui
- Y Cui
- Y Forterre
- Y Tang
- YF Cui
- Yifei Cui
- YJ Jiang
- YJ Jiang
- Z Feng
- Z Liu
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- Author
- Aaltonen L. (Lauri)
- Aaltonen V. (Vesa)
- Arvas M. (Mikko)
- Auge F. (Franck)
- Auranen A. (Annika)
- Auro K. (Kirsi)
- Auvinen P. (Paivi)
- Awaisa G. (Ghazal)
- Betts J. (Jo)
- Bhangale T. (Tushar)
- Bing N. (Nan)
- Biswas S. (Shameek)
- Blomster T. (Timo)
- Bowers N. (Natalie)
- Brein G. (Georg)
- Bronson P. (Paola)
- Call K. (Kathy)
- Carpen O. (Olli)
- Challis B. (Ben)
- Chang D. (Diana)
- Chatelain C. (Clement)
- Chen C.-Y. (Chia-Yen)
- Chen H. (Hao)
- Chen H. (Hubert)
- Chen X. (Xing)
- Chhibber A. (Aparna)
- Chu A. (Audrey)
- Close D. (David)
- Crohns M. (Marika)
- Dada A. (Alexander)
- Daly M. J. (Mark J.)
- Davis J. W. (Justin Wade)
- Diogo D. (Dorothee)
- Donner K. (Kati)
- Eaton S. (Susan)
- Ehm M. (Meg)
- Eicher J. (John)
- Eklund K. (Kari)
- Elenius K. (Klaus)
- Esmaeeli S. (Sahar)
- Farkkila M. (Martti)
- Fox C. (Caroline)
- Freimer N. B. (Nelson B.)
- Ganna A. (Andrea)
- Georgantas B. (Bob)
- Gerl M. J. (Mathias J.)
- Ghosh S. (Soumitra)
- Gordillo J. E. (Jorge Esparza)
- Gormley P. (Padhraig)
- Gossel M. (Matthias)
- Greenberg S. (Steven)
- Hannula-Jouppi K. (Katariina)
- Harju J. (Jarmo)
- Harju T. (Terttu)
- Harvima I. (Ilkka)
- Hassan S. (Shabbeer)
- Hautala N. (Nina)
- Havulinna A. S. (Aki S.)
- Heap G. (Graham)
- Hedman A. (Asa)
- Heikkinen S. (Sami)
- Hendolin M. (Minna)
- Hiekkalinna T. (Tero)
- Hiltunen M. (Mikko)
- Hinttala R. (Reetta)
- Hochfeld M. (Marla)
- Hoffman J. (Joshua)
- Holzinger E. (Emily)
- Hu X. (Xinli)
- Huhtakangas J. (Johanna)
- Huilaja L. (Laura)
- Hunkapiller J. (Julie)
- Hyvarinen K. (Kati)
- Isomaki P. (Pia)
- Jacob H. (Howard)
- Jalanko A. (Anu)
- Jarvensivu E. (Elina)
- Jauhiainen M. (Matti)
- Jimenez M. G. (Manuel Gonzalez)
- Joensuu H. (Heikki)
- John S. (Sally)
- Julkunen V. (Valtteri)
- Junttila J. (Juhani)
- Juonala M. (Markus)
- Jussila A. (Airi)
- Kaarniranta K. (Kai)
- Kaarteenaho R. (Riitta)
- Kahonen M. (Mika)
- Kaiharju E. (Essi)
- Kaipiainen-Seppanen O. (Oili)
- Kajanne R. (Risto)
- Kalaoja M. (Marita)
- Kallio L. (Lila)
- Kalpala K. (Kirsi)
- Kalviainen R. (Reetta)
- Kangasniemi E. (Eeva)
- Kankaanranta H. (Hannu)
- Kaprio J. (Jaakko)
- Karihtala P. (Peeter)
- Karjalainen J. (Juha)
- Karjalainen M. (Minna)
- Karlsson A. (Antti)
- Kaunisto M. (Mari)
- Kauppi P. (Paula)
- Kauppila S. (Saila)
- Kerchner G. (Geoff)
- Kettunen J. (Johannes)
- Kiiskinen T. T. (Tuomo T. J.)
- Kilpelainen E. (Elina)
- Kilpi T. (Terhi)
- Kiviniemi M. (Mikko)
- Klinger K. (Kathy)
- Klose C. (Christian)
- Kononen J. (Juha)
- Koskela J. T. (Jukka T.)
- Koskinen M. (Miika)
- Kosma V.-M. (Veli-Matti)
- Koulu L. (Leena)
- Kristiansson K. (Kati)
- Kujala U. (Urho)
- Kulkarni D. (Diptee)
- Kuopio T. (Teijo)
- Kurki M. (Mitja)
- Laakkonen E. (Eija)
- Laakso M. (Markku)
- Laaksonen R. (Reijo)
- Lahteenmaki S. (Sini)
- Laiho P. (Paivi)
- Laitinen T. (Tarja)
- Laivuori H. (Hannele)
- Landenpera S. (Sanni)
- Laukkanen J. (Jari)
- Laukkanen M. (Markku)
- Lehisto A. (Arto)
- Lehtonen A. (Anne)
- Lehtonen H. (Heli)
- Lemmela S. (Susanna)
- Lertratanakul A. (Apinya)
- Linden K. (Kari)
- Liu J. (Jimmy)
- Llorens V. (Vincent)
- Loboda A. (Andrey)
- Loukola A. (Anu)
- Lu T. (Tim)
- Luodonpaa M. (Marja)
- Lyhs U. (Ulrike)
- Makela T. (Tomi)
- Malarstig A. (Anders)
- Mannermaa A. (Arto)
- Mannikko L. (Lotta)
- Mantere T. (Tuomo)
- Maranville J. (Joseph)
- Mars N. (Nina)
- Marshal C. (Catherine)
- Matakidou A. (Athena)
- Matikainen N. (Niina)
- Mattsson H. (Hannele)
- McCarthy L. (Linda)
- McCarthy M. (Mark)
- McDonough S. (Stefan)
- Mehta V. (Vinay)
- Meretoja T. (Tuomo)
- Metsarinne K. (Kaj)
- Michon J. (John)
- Miller M. (Melissa)
- Muslin A. (Anthony)
- Niiranen T. (Teemu)
- Nunez-Fontarnau J. (Javier)
- Oh D. (Danny)
- Ollila T. (Terhi)
- Pakkanen R. (Raimo)
- Palin K. (Kimmo)
- Palomaki A. (Antti)
- Paloneva J. (Juha)
- Palotie A. (Aarno)
- Palta P. (Priit)
- Parkkinen J. (Jaakko)
- Parolo P. D. (Pietro Della Briotta)
- Parr K. (Kalle)
- Partanen J. (Jukka)
- Pelkonen M. (Margit)
- Peltola J. (Jukka)
- Peltonen S. (Sirkku)
- Perola M. (Markus)
- Peterson A. (Andrew)
- Petrovski S. (Slave)
- Pihlajamaki J. (Jussi)
- Pikkarainen S. (Sampsa)
- Pirila L. (Laura)
- Pirinen M. (Matti)
- Pitkanen K. (Kimmo)
- Pitkaranta A. (Anne)
- Plenge R. (Robert)
- Podgornaia A. (Anna)
- Popovic R. (Relja)
- Pulford D. (David)
- Pulkki K. (Kari)
- Pylkas K. (Katri)
- Quarless D. (Danjuma)
- Rahimov F. (Fedik)
- Ramo J. T. (Joel T.)
- Remes A. (Anne)
- Riley-Gillis B. (Bridget)
- Rinne J. (Juha)
- Ripatti P. (Pietari)
- Ripatti S. (Samuli)
- Ritari J. (Jarmo)
- Rivas M. (Manuel)
- Runz H. (Heiko)
- Salmi T. (Teea)
- Salomaa V. (Veikko)
- Savinainen K. (Kimmo)
- Schleutker J. (Johanna)
- Schutzman J. (Jennifer)
- Seitsonen S. (Sanna)
- Service S. K. (Susan K.)
- Shcherban A. (Anastasia)
- Siirtola H. (Harri)
- Simons K. (Kai)
- Sinisalo J. (Juha)
- Sipila T. (Tuomas)
- Sipila T. P. (Timo P.)
- Sistonen T. (Tuuli)
- Smaoui N. (Nizar)
- Soderlund S. (Sanni)
- Soini S. (Sirpa)
- Soininen H. (Hilkka)
- Stitziel N. O. (Nathan O.)
- Strauss E. (Erich)
- Surma M. A. (Michal A.)
- Tabassum R. (Rubina)
- Tabuenca J. G. (Javier Gracia)
- Tasanen K. (Kaisa)
- Taskinen M.-R. (Marja-Riitta)
- Teng E. (Edmond)
- Tienari P. (Pentti)
- Tuomi T. (Tiinamaija)
- Tuovila O. (Outi)
- Turunen J. (Joni)
- Usiskin K. (Keith)
- Uusitalo H. (Hannu)
- Uusitalo-Jarvinen H. (Hannele)
- Vainio S. (Seppo)
- Virolainen P. (Petri)
- Voutilainen M. (Markku)
- Wahlfors T. (Tiina)
- Wang C. (Clarence)
- Wang X. (Xulong)
- Waring J. (Jeff)
- Waring J. (Jeffrey)
- Waterworth D. (Dawn)
- Whelan C. (Christopher)
- Wong R. (Regis)
- Wu Y. (Ying)
- Xu E. (Ethan)
- Xu F. (Fanli)
- Yang R. (Robert)
- Zhou W. (Wei)
- Ziemann A. (Adam)
- Publication venue
- Springer Nature
- Publication date
- 01/01/2019
- Field of study
Abstract
Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD
Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
- Author
- Aaltonen L. (Lauri)
- Aaltonen V. (Vesa)
- Abe N. (Namiko)
- Abecasis G. (Goncalo)
- Albert C. (Christine)
- Almasy L. (Laura)
- Alonso A. (Alvaro)
- Ament S. (Seth)
- Anderson P. (Peter)
- Antonacci-Fulton L. (Lucinda)
- Applebaum-Bowden D. (Deborah)
- Aragam K. (Krishna)
- Arden M. (Moscati)
- Arking D. (Dan)
- Arnett D. K. (Donna K.)
- Arvas M. (Mikko)
- Ashley-Koch A. (Allison)
- Aslibekyan S. (Stella)
- Assimes T. L. (Themistocles L.)
- Auer P. (Paul)
- Auge F. (Franck)
- Auranen A. (Annika)
- Auro K. (Kirsi)
- Auvinen P. (Pivi)
- Avramopoulos D. (Dimitrios)
- Awaisa G. (Ghazal)
- Ballantyne C. M. (Christie M.)
- Barnard J. (John)
- Barnes K. (Kathleen)
- Barr R. G. (R. Graham)
- Barron-Casella E. (Emily)
- Beaty T. (Terri)
- Becker D. (Diane)
- Becker J. P. (Julia Powers)
- Becker L. C. (Lewis C.)
- Beer R. (Rebecca)
- Begum F. (Ferdouse)
- Beitelshees A. (Amber)
- Benjamin E. (Emelia)
- Betts J. (Jo)
- Bezerra M. (Marcos)
- Bhangale T. (Tushar)
- Bielak L. (Larry)
- Bielak L. F. (Lawrence F.)
- Bing D. C. (David Close Marla Hochfeld Nan)
- Bisl J. C. (Joshua C.)
- Biswas S. (Shameek)
- Blackwel T. (Thomas)
- Blangercy J. (John)
- Blomster T. (Timo)
- Boerwinkle E. (Eric)
- Boorgula M. P. (Meher Preethi)
- Bowden D. W. (Donald W.)
- Bowers N. (Natalie)
- Bowler R. (Russell)
- Brein G. (Georg)
- Brody J. A. (Jennifer A.)
- Broecke U. (Ulrich)
- Bronson P. (Paola)
- Broome J. G. (Jai G.)
- Bunting K. (Karen)
- Burchard E. (Esteban)
- Buth E. (Erin)
- Cade B. E. (Brian E.)
- Call K. (Kathy)
- Cardwel J. (Jonathan)
- Carty C. (Cara)
- Casaburi R. (Richard)
- Casella J. (James)
- Chaffin M. (Mark)
- Challis B. (Ben)
- Chang C. (Christy)
- Chang D. (Diana)
- Chang Y.-C. (Yi-Cheng)
- Chasman D. (Daniel)
- Chatelain C. (Clement)
- Chavan S. (Sameer)
- Chen B.-J. (Bo-Juen)
- Chen C.-Y. (Chia-Yen)
- Chen H. (Hao)
- Chen H. (Hubert)
- Chen W.-M. (Wei-Min)
- Chen X. (Xing)
- Chen Y. I. (Yii-Der, I)
- Chhibber A. (Aparna)
- Choi S. H. (Seung Hoan)
- Choi W. J. (Won Jung)
- Chol M. (Michael)
- Choy D. (David)
- Chu A. (Audrey)
- Chuang L.-M. (Lee-Ming)
- Chung M. (Mina)
- Connell J. O. (Jeff O.)
- Connell J. R. (Jeffrey R. O.)
- Connor T. O. (Tim O.)
- Conomos M. P. (Matthew P.)
- Cornell E. (Elaine)
- Correa A. (Adolfo)
- Crapo J. (James)
- Crohns M. (Marika)
- Cupples L. A. (L. Adrienne)
- Curran J. E. (Joanne E.)
- Curtis J. (Jeffrey)
- Custer B. (Brian)
- Dada A. (Alexander)
- Daly M. (Mark)
- Daly M. J. (Mark J.)
- Damcott C. (Coleen)
- Darbar D. (Dawood)
- Das S. (Sayantan)
- David S. (Sean)
- Davis C. (Colleen)
- Davis J. W. (Justin Wade)
- Daya M. (Michelle)
- de Andrade M. (Mariza)
- de Vries P. S. (Paul S.)
- DeBaunuo M. (Michael)
- Devine R. D. (Ranjan Deka Dawn DeMeo Scott)
- Diogo D. (Dorothee)
- Do R. (Ron)
- Doddapaneni H. (Harsha)
- Donner K. (Kati)
- Duan Q. (Qing)
- Duggirala Q. R. (Qing Ravi)
- Durda J. P. (Jon Peter)
- Dutcher S. (Susan)
- DutcherE S. K. (Susan K.)
- Eaton C. (Charles)
- Eaton S. (Susan)
- Ehm M. (Meg)
- Eicher J. (John)
- Eklund K. (Kari)
- Ekunwe L. (Lynette)
- Elenius K. (Klaus)
- Ellinor P. T. (Patrick T.)
- Emery L. S. (Leslie S.)
- Esmaeeli S. (Sahar)
- Farber C. (Charles)
- Farnaml L. (Leanna)
- Fingerlin T. (Tasha)
- Flickinger M. (Matthew)
- Fornage M. (Myriam)
- Fox C. (Caroline)
- Franceschini N. (Nora)
- Freedman B. I. (Barry, I)
- Frkkil M. (Martti)
- Fu M. (Mao)
- Fullerton S. M. (Stephanie M.)
- Fulton L. (Lucinda)
- Gabriel S. (Stacey)
- Gan W. (Weiniu)
- Ganna A. (Andrea)
- Gao Y. (Yan)
- Gass M. (Margery)
- Ge B. (Bruce)
- Geng X. P. (Xiaoqi Priscilla)
- Georgantas B. (Bob)
- Germer S. (Soren)
- Germer S. (Soren)
- Ghosh S. (Soumitra)
- Gibbs R. A. (Richard A.)
- Gignoux C. (Chris)
- Gladwin M. (Mark)
- Glahn D. (David)
- Gogarten S. (Stephanie)
- Gong D.-W. (Da-Wei)
- Gordillo J. E. (Jorge Esparza)
- Goring H. (Harald)
- Gormle P. Y. (Padhraig Y.)
- Gossel M. (Matthias)
- Graham S. E. (Sarah E.)
- Greenberg S. (Steven)
- Gu C. C. (C. Charles)
- Guan Y. (Yue)
- Guo X. (Xiuqing)
- Haessler J. (Jeff)
- Hall M. (Michael)
- Hannula-Jouppi K. (Katariina)
- Harju J. (Jarmo)
- Harju T. (Terttu)
- Harris D. (Daniel)
- Harvima I. (Ilkka)
- Hautala N. (Nina)
- Havulinna A. (Aki)
- Hawle N. Y. (Nicola Y.)
- He J. (Jiang)
- Heap G. (Graham)
- Heavner B. (Ben)
- Heckbert S. (Susan)
- Heikkinen S. (Sami)
- Hendolin M. (Minna)
- Hernandez R. (Ryan)
- Herrington D. (David)
- Hersh C. (Craig)
- Hidalgo B. (Bertha)
- Hiekkalinna T. (Tero)
- Hiltunen M. (Mikko)
- Hinttala R. (Reetta)
- Hixson J. (James)
- Hoffman J. (Joshua)
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- Publication venue
- Springer Nature
- Publication date
- 01/01/2021
- Field of study
Abstract
Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids
New insights into the genetic etiology of Alzheimer’s disease and related dementias
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- Aaltonen L.
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- Xuan Liu
- Yanbing Wang
- Yanek L.
- Yang Q.
- Yang Y.
- Yannakoulia M.
- Yaqub A.
- Yasaman Saba
- Yash Patel
- Yeunjoo E Song
- Yi Zhao
- Ying Wu
- Yoav Ben-Shlomo
- Yogen Patel
- Younkin S. G.
- Yu C. -E.
- Yu L.
- Yuanchao Zhang
- Yuk Yee Leung
- Yunfeng Huang
- Yunju Yang
- Zare H.
- Zdenka Pausova
- Zhang X.
- Zhang Y.
- Zhao Y.
- Zhao Y.
- Zhou W.
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- Ziemann A.
- Zoia C. P.
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- Zulaica M.
- Zulma Sevillano
- Álvarez V.
- Åsa Hedman
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
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
- Carol Ann Linebarger
- Carol Kauffman
- Carol L. Mitchell
- Carolene Stephenson
- Caroline Greene
- Carolyn Scatamacchia
- Carolyn Tran
- Carrie Johnston
- Carrie Sopher
- Catherine A. Bunce
- Catherine Mary Healy
- Catherine Q. Gular
- Cathy Laflan
- Cecilia McKeown-Bragas
- Celia Gonzalez
- Celia Maxwell
- Charles Harper
- Charles M. Fogarty
- Charlotte-Paige Rolle
- Charnell Cromer
- Chelsea Miles
- Chelsie Nutsch
- Chelsie Nutsch
- Chen S. Tan
- Chenchen Yu
- Cheryl Nuss
- Cheryl Young
- Chimeremma Nnadi
- Chinar Desai
- Christian Tomaszewski
- Christina A. Rostad
- Christina Bacher
- Christina Kennelly
- Christine Akamine
- Christine B. Turley
- Christine Hull
- Christine Wilson
- Christopher Carpenter
- Christopher Dedon
- Christopher Galloway
- Christopher Matich
- Christy Schmeck
- Christy Sweet
- Clarence B. Creech II
- Clarisse Baudelaire
- Claudia De La Matta Rodriguez
- Claudia Espinosa
- Claudio Nuñez Lagos
- Clint C. Guillory
- Clint Wilson
- Codi M. Anthony
- Colleen F. Kelley
- Colleen Jacobsen
- Connie Moya
- Cora Sonnier
- Corey G. Anderson
- Corey M. Chen
- Cornell Calinescu
- Corrina Pavetto
- Cortney Burch
- Cory J. Huffine
- Craig Dietz
- Cristina Cicogna
- Crystal Rowell
- Cynthia Becher Strout
- Cynthia Brown
- Cynthia Bueno
- Cynthia L. Gay
- Cynthia L. Monaco
- Cynthia Montano-Pereira
- Cyrus Hoseyni
- Dakotah C. Lane
- Dalia Tovar
- Daniel Duncanson
- Daniel Hoft
- Daniel Kaul
- Daniel S. Graciaa
- Daniel T. Lawler
- Daniela Pineda Méndez
- Danielle Raley
- Danny Sugimoto
- Danyel Johnson
- Darlene Bartilucci
- David B. Musante
- David Beckmann
- David Browder
- David Dellaero
- David Fitz-Patrick
- David Halpert
- David I. Bernstein
- David J. Diemert
- David J. Ensz
- David Kline
- David L. Fried
- David Metzger
- David Pampe
- David Pitrak
- David R. Andes
- David Rosenberg
- David Tatelbaum
- David Wohl
- Dawn Furey
- Dawn Robison
- Dean Follmann
- Dean M. Boswell
- Deanna Cooper
- Debora Dunbar
- Deborah A. Theodore
- Deborah Murray
- Debra B. Schroeck
- Delia Bullock
- Denis Tarakjian
- Denise Casey
- Denise Roadman
- Denise Sample
- Denisse Alejandra González Estrada
- Derek Lewis
- Derek M. Smith
- Destiny S. Heinzig-Cartwright
- Diana Badillo
- Diana F. Florescu
- Diana Vegas
- Dianca Sierra
- Diane H. Johnson
- Dilek Ince
- Dima Dandachi
- Dirk Heerwegh
- Dolores Rijos
- Donald M. Brandon
- Donald Quinn
- Donna Percy
- Doris Franco-Vitteri
- Douglas S. Denham
- E. Javier Pretell Alva
- Edgar Garcia
- Edith Swann
- Eduardo Gabriel Vázquez Saldaña
- Edward C. Jones-López
- Edward E. Walsh
- Edward Ellerbeck
- Edward M. Tavel Jr.
- Elham Ghadishah
- Elie Gharib
- Elisa Swieboda
- Elissa Malkin
- Elizabeth Barranco-Santana
- Elizabeth Bennett
- Elizabeth Bruce
- Elizabeth Danford
- Elizabeth Duke
- Elizabeth E. Robison
- Elizabeth Everette
- Elizabeth Formentini
- Elizabeth Hammershaimb
- Elizabeth Parker
- Elizabeth Secord
- Ellie Carmody
- Elliot DeHaan
- Elwaleed Elnagar
- Emily Degan
- Emily Oppenheim
- Emma Bainbridge
- Emmanuel B. Walter
- Eneyda Giuvanela Llerena Zegarra
- Enrique Ocaña
- Eric A. Meyerowitz
- Eric Bravo
- Eric McGrath
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- Sybil G. Hosek
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- Teresa Becker
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- Terry L. Poling
- Terry Piedra
- Theresa Hegmann
- Thomas B. Campbell
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- Thomas C.S. Martin
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- Thomas Patterson
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- 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