5 research outputs found
Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution
- Author
- Abril G. (Gabriela)
- Anders R.A. (Robert)
- Ewing A.D. (Adam D.)
- Gacita A. (Anthony)
- Gillis A.J.M. (Ad)
- Hruban R.H. (Ralph)
- Iacobuzio-Donahue C.A.
- Kazazian H.H. (Haig)
- Kim M.-S. (Min-Sik)
- Kinzler K.W. (Kenneth W.)
- Looijenga L.H.J. (Leendert)
- Ma F. (Florence)
- Makohon-Moore A. (Alvin)
- Manda S.S. (Srikanth S.)
- Pandey A. (Akhilesh)
- Pereira G. (Gavin)
- Romans K.E. (Katharine E.)
- Solyom S. (Szilvia)
- Vogelstein B. (Bert)
- Wood L.D. (Laura D.)
- Xing D. (Dongmei)
- Publication venue
- 'Cold Spring Harbor Laboratory'
- Publication date
- 01/10/2015
- Field of study
Somatic L1 retrotransposition events have been shown to occur in epithelial cancers. Here, we attempted to determine how early somatic L1 insertions occurred during the development of gastrointestinal (GI) cancers. Using L1-targeted resequencing (L1-seq), we studied different stages of four colorectal cancers arising from colonic polyps, seven pancreatic carcinomas, as well as seven gastric cancers. Surprisingly, we found somatic L1 insertions not only in all cancer types and metastases but also in colonic adenomas, well-known cancer precursors. Some insertions were also present in low quantities in normal GI tissues, occasionally caught in the act of being clonally fixed in the adjacent tumors. Insertions in adenomas and cancers numbered in the hundreds, and many were present in multiple tumor sections, implying clonal distribution. Our results demonstrate that extensive somatic insertional mutagenesis occurs very early during the development of GI tumors, probably before dysplastic growth
Young and Intermediate-Age Distance Indicators
- Author
- A. Bhardwaj
- A. Bhardwaj
- A. Bhardwaj
- A. Bressan
- A. Gallenne
- A. GarcĂa-Varela
- A. Nakagawa
- A. Nakagawa
- A. Nakagawa
- A. Siebert
- A. Udalski
- A. Udalski
- A.A. Cole
- A.G. Riess
- A.G. Riess
- A.J. Cuesta
- A.J. Monson
- A.J. Monson
- A.K. Dambis
- A.M. Jacyszyn-Dobrzeniecka
- Akiharu Nakagawa
- Anupam Bhardwaj
- B. Aringer
- B. PaczyĆski
- B. Schölkopf
- B. Sesar
- B. Westerlund
- B. Zhang
- B.F. Madore
- B.L. Tatton
- C. Alcock
- C. Dvorkin
- C. Min
- C. Ngeow
- C. Ngeow
- C. Wegg
- C.-C. Ngeow
- C.-C. Ngeow
- C.-C. Ngeow
- C.-C. Ngeow
- C.A. Haniff
- C.D. Laney
- C.D. Laney
- C.G. RomĂĄn-ZĂșñiga
- C.W. McAlary
- D. Graczyk
- D. Huber
- D. Minniti
- D. Nyu
- D. Stello
- D. Stello
- D.E. Knuth
- D.J. Marshall
- D.L. Nidever
- E. Hubble
- E. Kapakos
- E. Puzeras
- E.F. Schlafly
- E.P. Hubble
- ESA
- F. Caputo
- F. Leeuwen van
- F. Leeuwen van
- F. Leeuwen van
- G. Bono
- G. Bono
- G. Bono
- G. Bono
- G. Bono
- G. Fiorentino
- G. Fiorentino
- G. Marchi De
- G. PietrzyĆski
- G. PietrzyĆski
- G. PietrzyĆski
- G.A. Tammann
- G.F. Benedict
- G.G. Fazio
- G.H. Rieke
- G.H. Rieke
- G.M. Green
- G.P. Benedetto di
- G.R. Ricker
- H. Kobayashi
- H. Nakanishi
- H. Rauer
- H.-B. Yuan
- H.R. Neilson
- H.S. Leavitt
- I. SoszyĆski
- I. SoszyĆski
- I. SoszyĆski
- J. Bovy
- J. Storm
- J. Storm
- J. Storm
- J.-J. Ren
- J.A. Cardelli
- J.A. Rich
- J.F. Koerwer
- J.P. Beaulieu
- J.P. Gardner
- Jesper Storm
- K. Fricke
- K. Kusuno
- K.A.G. Olsen
- K.M. Flaherty
- K.Z. Stanek
- K.Z. Stanek
- Kh.S. Rezaei
- L. Girardi
- L. Girardi
- L. Girardi
- L. Girardi
- L. Inno
- L. Inno
- L. Inno
- L.D. Matthews
- L.D. Matthews
- L.M. Macri
- Laura Inno
- M. Marconi
- M. Marconi
- M. Marengo
- M. Marengo
- M. Marengo
- M. Marengo
- M. Romaniello
- M. Salaris
- M. Shintani
- M. Wyman
- M.-R.L. Cioni
- M.A.C. Perryman
- M.E.K. Williams
- M.H. Pinsonneault
- M.L. McCall
- M.M. Phillips
- M.S. Xiang
- M.W. Feast
- M.W. Feast
- M.W. Feast
- M.W. Werner
- Massimo Marengo
- N. Kawaguchi
- N. Matsunaga
- N. Matsunaga
- N. Matsunaga
- N. Zacharias
- N.E. Evans
- N.L. Chapman
- N.R. Evans
- N.R. Simon
- O. Bienaymé
- O. Pejcha
- O.L. Creevey
- P. Barmby
- P. Fouque
- P. Fouqué
- P. Kervella
- P. Kervella
- P. Whitelock
- P.R. Wood
- Planck Collaboration
- R. Grijs de
- R. Grijs de
- R. Haschke
- R. Haschke
- R. Indebetouw
- R. Kamohara
- R.C. Kennicutt Jr.
- R.D. Cannon
- R.E. Luck
- R.I. Anderson
- R.I. Anderson
- R.M. Cutri
- R.P. Martin
- R.V. Jones
- S. Bergh van den
- S. Bilir
- S. Kanbur
- S. Nishiyama
- S. Roeser
- S. Rubele
- S. Subramanian
- S. Subramanian
- S. Subramanian
- S. Subramanian
- S. Subramanian
- S.C. Keller
- S.D. Friedman
- S.E. Persson
- S.M. Andrievsky
- Smitha Subramanian
- T. Kamezaki
- T. Kamezaki
- T. Kamezaki
- T. Kamezaki
- T. Kurayama
- T.G. Barnes
- V. Ripepi
- V. Scowcroft
- V. Scowcroft
- V. Scowcroft
- V.M.R. Muggeo
- V.R.M. Muggeo
- W. Dehnen
- W.H.T. Vlemmings
- W.H.T. Vlemmings
- W.L. Freedman
- W.L. Freedman
- W.L. Freedman
- W.L. Freedman
- W.L. Freedman
- X.-W. Liu
- Y. Asaki
- Y. Huang
- Y. Huang
- Y. Ita
- Y.K. Choi
- Yang Huang
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Whole-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
- AgĂŒero 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.
- AlBardis H.
- Albeladi M.
- Albesher N.
- Albrich W.
- AlDhawi N.
- Aldridge J.
- Aleagha Afshar Etemadi
- Alexander Peter.
- Alfonso J.
- Alghamdi B.
- Alghamdi J.
- Ali A.
- Ali Altaf
- Ali I.A.M.
- Ali Syamlan
- Aliannejad Rasoul
- Aljawini N.
- AlJohani S.
- Alkwai S.
- Allan A.
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- Allan J.
- Alldis Zoe
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- Allibone S.
- Allison K.S.
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- Ally S.M.
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- Almalki F.
- Almohammed I.
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- Alqubaishi F.
- Alrashed M.
- Alshareef A.
- Alsolm E.
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- Altabaibeh A.
- Alvaro A.
- AlZahrani D.
- Amin V.
- Amirsavadkouhi Ali
- Amitrano Sara
- Anastasescu E.
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- Andolfo I.
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- Andreucci E.
- Andrew Angela
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- Ă svold BjĂžrn Olav
- Publication venue
- Publication date
- 01/01/2022
- Field of study
Altres 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
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)
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- An P. (Ping)
- Ardlie K.G. (Kristin)
- Ardlie K.G. (Kristin)
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- Aulchenko Y.S. (Yurii S.)
- Aulchenko Y.S. (Yurii S.)
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- Kronenberg F. (Florian)
- Kumari M. (Meena)
- Kuusisto J. (Johanna)
- Kuzawa C.W. (Christopher W.)
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- KÀhönen M. (Mika)
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- Laakso M. (Markku)
- Laakso M. (Markku)
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- Lajunen T. (Taina)
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- Lange L.A. (Leslie)
- Langenberg C. (Claudia)
- Langenberg C. (Claudia)
- Langenberg C. (Claudia)
- Langenberg C. (Claudia)
- Lathrop G. (GMark)
- Launer L.J. (Lenore J.)
- Lauritzen T. (Torsten)
- Lawlor D.A. (Debbie)
- Lecoeur C. (CĂ©cile)
- Lee J.-Y. (Jong-Young)
- LehtimÀki T. (Terho)
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- Li M. (Man)
- Li M. (Man)
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- Lindgren C.M. (Cecilia M.)
- Lindgren C.M. (Cecilia)
- Liu C.-T. (Ching-Ti)
- Liu Y. (YongMei)
- Lohman K. (Kurt)
- Lokki M.L.
- Loo B.-M. (Britt-Marie)
- Loos R.J.F. (Ruth)
- Loos R.J.F. (Ruth)
- Loos R.J.F. (Ruth)
- Luan J. (Jianâan)
- Luan J. (Jianâan)
- Luben R.N. (Robert)
- Lucas G. (Gavin)
- Lyssenko V. (Valeriya)
- Lyssenko V. (Valeriya)
- LyytikÀinen L.-P. (Leo-Pekka)
- MAGIC Consortium
- Magnusson P.K. (Patrik)
- Magnusson P.K.E. (Patrik K. E.)
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- Manning A.K. (Alisa K.)
- Manning A.K. (Alisa)
- Marmot M. (Michael)
- Marre M. (Michel)
- Marroni F. (Fabio)
- Martin N.G. (Nicholas)
- Martinez-Larrad M.T. (Maria Teresa)
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- McArdle W.L. (Wendy)
- McAteer J.B. (Jarred)
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- McCarroll S.A. (Steven)
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- MuTHER Consortium
- MĂ€gi R. (Reedik)
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- van Duijn C. (Cornelia)
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- Vogelzangs N. (Nicole)
- Voight B.F. (Benjamin F.)
- Voight B.F. (Benjamin F.)
- Voight B.F. (Benjamin)
- Vollenweider P. (Peter)
- Vollenweider P. (Peter)
- Vollenweider P. (Peter)
- Waeber G. (GĂ©rard)
- Waeber G. (GĂ©rard)
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- Wild S.H. (Sarah)
- Willems van Dijk J.A.P. (Ko)
- Willems S.M. (Sara)
- Willems-vanDijk K. (Ko)
- Willemsen G.
- Willemsen G.A.H.M. (Gonneke)
- Willer C.J. (Cristen J.)
- Willer C.J. (Cristen)
- Williams G.H. (Gordon)
- Wilson J.F. (James F.)
- Wilson J.F. (James)
- Wilson J.G. (James G.)
- Winkler T.W. (Thomas W.)
- 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)
- Ădonnell C.J. (Christopher)
- Publication venue
- Publication date
- 01/01/2012
- Field of study
Circulating 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 = 4.5Ă10â8- 1.2 Ă10â43). 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<3Ă10â4). 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 = 4.3Ă10â3, n = 22,044), increased triglycerides (p = 2.6Ă10â14, n = 93,440), increased waist-to-hip ratio (p = 1.8Ă10â5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4Ă10â3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL- cholesterol concentrations (p = 4.5Ă10â13, n = 96,748) and decreased BMI (p = 1.4Ă10â4, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance
Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes
- Author
- Abecasis G. (Goncalo)
- Abecasis G.R. (Gonçalo)
- Abecasis G.R. (Gonçalo)
- Aben K.K.H. (Katja)
- Absher D. (Devin)
- Absher D. (Devin)
- Aherrahrou Z. (Zouhair)
- Ahlqvist E. (Emma)
- Ahmadi K.R. (Kourosh)
- Ahmed N. (Nabeel)
- Alavere H. (Helene)
- Alibrandi M.T.S. (Maria)
- Allayee H. (Hooman)
- Allen H.L.
- Almgren P. (Peter)
- Altshuler D. (David)
- Amin N. (Najaf)
- Anand S.S. (Sonia)
- Andersen K.K. (Karl)
- Ardissino D. (Diego)
- Ardlie K.G. (Kristin)
- Armitage J. (Jane)
- Arnold A.M. (Alice)
- Aspelund T. (Thor)
- Assimes T.L. (Themistocles)
- Assmann G. (Gerd)
- Aulchenko Y.S. (Yurii)
- Azhar M. (Muhammad)
- Balkau B. (Beverley)
- Ball S.G. (Stephen G.)
- Barbalic M. (maja)
- Barker A.M. (Adam)
- Barlassina C. (Christina)
- Barlera S. (Simona)
- Barnes D. (Daniel)
- Barnes T.A. (Timothy)
- Barrett A. (Angela)
- Barroso I.E. (InĂȘs)
- Bataille V. (Veronique)
- Becker D.M. (Diane)
- Becker L.C. (Lewis)
- Beckmann J.S. (Jacques)
- Beckmann J.S. (Jacques)
- Beilby J.P. (John)
- Bell J.T. (Jordana)
- Ben-Shlomo Y.
- Ben-Shlomo Y. (Yoav)
- Bennett A.J. (Amanda)
- Berger K. (Klaus)
- Bergman R.N. (Richard N.)
- Bergmann S.M. (Sven)
- Berndt S.I. (Sonja)
- Biebermann H. (Heike)
- Bis J.C. (Joshua)
- Blagieva R. (Roza)
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- Blankenberg S. (Stefan)
- Boehm B.O. (Bernhard)
- Boehm B.O. (Bernhard)
- Boehnke M. (Michael)
- Boeing H. (Heiner)
- Boeing H. (Heiner)
- Boekholdt S.M. (Matthijs)
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- Boomsma D.I. (Dorret)
- Borecki I.B. (Ingrid)
- Bornstein S.R. (Stefan R.)
- Bornstein S.R. (Stefan)
- Boström K.B. (Kristina Bengtsson)
- Bouatia-Naji N. (Nabila)
- Bowman L.
- Braund P.S. (Peter)
- Bravenboer B. (Bert)
- Buchanan T.A. (Thomas)
- Bumpstead S. (Suzannah)
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- Busonero F.
- Buysschaert I. (Ian)
- Cambien F. (François)
- Campbell H. (Harry)
- Cappuccio F.P. (Francesco P.)
- Cappuccio F.P. (Francesco)
- Carlquist J.F. (John)
- Cauchi S. (Stephane)
- Caulfield M. (Mark)
- Cavalcanti-Proença C. (Christine)
- Chambers J.C. (John C.)
- Chambers J.C. (John)
- Chanock S.J. (Stephen)
- Charpentier G. (Guillaume)
- Chasman D.I. (Daniel)
- Chatterjee N. (Nilanjan)
- Chen C.-M. (Chih-Mei)
- Chen H. (Han)
- Chen L. (Li)
- Chines P.S. (Peter)
- Cichon S. (Sven)
- Clarke R.
- Clarke R. (Robert)
- Codd V. (Veryan)
- Coin L. (Lachlan)
- Coin L. (Lachlan)
- Collins F.S. (Francis S.)
- Collins F.S. (Francis)
- Collins F.S. (Francis)
- Connell J. (John)
- Cooper C. (Charles)
- Cooper C.C. (Cyrus C.)
- Cooper M.N. (Matthew N.)
- Cooper M.N. (Matthew)
- Cornelis M. (Marilyn)
- Couper D.J. (David)
- Crawford G. (Gabe)
- Cupples L.A. (Adrienne)
- Daly M.J. (Mark)
- Dam R.M. (Rob) van
- Danesh J. (John)
- Davies R.W. (Robert)
- Day I.N.M. (Ian N.M.)
- Day I.N.M. (Ian)
- Dedoussis G.V. (George)
- Dedoussis G.V. (George)
- Dedoussis G.V. (George)
- Dehghan A. (Abbas)
- Deloukas P. (Panagiotis)
- Demissie S. (Serkalem)
- Den Heijer M. (Martin)
- Dennison E.M. (Elaine)
- Dermitzakis E.T. (Emmanouil T.)
- Devaney J.M. (Joseph M.)
- Di Meglio P. (Paola)
- Diemert P. (Patrick)
- Dimas A.S. (Antigone)
- Dina C. (Christian)
- Dixon A.L. (Anna)
- Do R. (Ron)
- Doering A. (Angela)
- Doney A.S.F. (Alex)
- Donnelly P. (Peter)
- Duan J. (Jubao)
- Duijn C.M. (Cornelia) van
- Dupuis J. (Josée)
- Durbin R. (Richard)
- Ebrahim S. (Shah)
- Ebrahim S. (Shanil)
- Eifert S. (Sandra)
- Eiriksdottir G. (Gudny)
- El Mokhtari N.E. (Nour Eddine)
- Elliott A.L. (Amanda)
- Elliott K.S. (Katherine)
- Elliott P. (Paul)
- Ellis S.G. (Stephen)
- Elosua R. (Roberto)
- Engert J.C. (James C.)
- Epstein S.E. (Stephen)
- Erdmann J. (Jeanette)
- Erdos M.R. (Michael)
- Eriksson P. (Per)
- Esko T. (Tonu)
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- Eury E. (Elodie)
- Faire U. (Ulf) de
- Farooqi I.S. (I. Sadaf)
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- Ferrannini E. (Ele)
- Ferreira T. (Teresa)
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- Johnson P. (Paul)
- Johnson P.R.V. (Paul R.V.)
- Johnson T. (Toby)
- Johnson T. (Toby)
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- Kaprio J. (Jaakko)
- Kaprio J. (Jaakko)
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- Kettunen J. (Johannes)
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- Kolovou G. (Genovefa)
- Kong A. (Augustine)
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- Kraft P. (Peter)
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- Lettre G. (Guillaume)
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- Levinson D.F. (Douglas)
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- Li S. (Shengxu)
- Li X. (Xiaohui)
- Liang L. (Liming)
- Lieb W. (Wolfgang)
- Lieverse A.G. (Aloysius)
- Linksted P. (Pamela)
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- Liu J. (Jianjun)
- Lokki M.L.
- Loley C. (Christina)
- Loos R.J.F. (Ruth)
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- Luan J.
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- Lyssenko V. (Valeriya)
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- Mallick C.B. (Chandana Basu)
- Mannila M.N. (Maria Nastase)
- Manning A.K. (Alisa)
- Mannucci P.M. (Pier)
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- Marre M. (Michel)
- Martin N.G. (Nicholas)
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- McCarroll S.A. (Steven)
- McCarthy A. (Anne)
- McCarthy M. (Mark)
- McCarthy M.I. (Mark I.)
- McCarthy M.I. (Mark)
- McCulloch L.J. (Laura)
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- McPherson R. (Ruth)
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- Merlini P.A. (Pier Angelica)
- Metspalu A. (Andres)
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- Min J. (Josine)
- Mohlke K.L. (Karen L.)
- Monda K.L. (Keri)
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- Montgomery G.W. (Grant)
- Mooser V. (Vincent)
- Morgan T. (Thomas)
- Morken M.A. (Mario)
- Morris A.D. (Andrew)
- Morris A.P. (Andrew)
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- Mulic R. (Rosanda)
- Munroe P. (Patricia)
- Munroe P.B. (Patricia B.)
- Munzel T. (Thomas)
- Musunuru K. (Kiran)
- Myers R.H. (Richard)
- MĂ€gi R. (Reedik)
- MĂ€larstig A. (Anders)
- MĂ€rz W. (Winfried)
- Nahrstaedt J. (Janja)
- Narisu N. (Narisu)
- Narisu N. (Narisu)
- Navarro P. (Pau)
- Nelis M. (Mari)
- Nelson C.P. (Christopher P.)
- Nemesh J. (James)
- Nestle F.O. (Frank)
- Neville M.J. (Matthew)
- Ngwa J.S.
- Nica A. (Alexandra)
- Nieminen M.S. (Markku)
- Nilsson P. (Peter)
- Nisbet J. (James)
- North K.E. (Kari)
- Nyholt D.R. (Dale)
- Nöthen M.M. (Markus)
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- O'Donnell C.J. (Christopher)
- O'Rahilly S. (Stephen)
- O'Rahilly S. (Stephen)
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- Offer A. (Alison)
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- Osmond C. (Clive)
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- OÂŽConnell J.R.
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- Pascoe L. (Laura)
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- Peden J. (John)
- Pedersen O. (Oluf)
- Pellikka N. (Niina)
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- Penninx B.W.J.H.
- Perola M. (Markus)
- Perola M. (Markus)
- Perry J.R.B. (John)
- Peters A. (Annette)
- Peters M.J. (Marjolein)
- Petersen A.K.
- Peto R. (R.)
- Petrie J.R. (John)
- Peyvandi F. (Flora)
- Pichler I. (Irene)
- Pietilainen K.H. (Kirsi Hannele)
- Platou C. (Carl)
- Platou C.P. (Carl)
- Polasek O. (Ozren)
- Potter S.C. (Simon)
- Pramstaller P.P. (Peter P.)
- Preuss M. (Michael)
- Proença C. (Christine)
- Prokopenko I. (Inga)
- Prokopenko I. (Inga)
- Purcell S. (Shaun)
- Qi L. (Lu)
- Quertermous T. (Thomas)
- Quyyumi A.A. (Arshed)
- Rader D.J. (Daniel)
- Rafelt S. (Suzanne)
- Raitakari O. (Olli)
- Raitakari O.T. (Olli T.)
- Rallidis L.S. (Loukianos)
- Randall J.C. (Joshua)
- Rasheed A. (Asif)
- Rathmann W. (Wolfgang)
- Rathmann W. (Wolfgang)
- Raychaudhuri S. (Soumya)
- Rayner N.W. (N. William)
- Rayner N.W. (Nigel William)
- Reilly M.P. (Muredach P.)
- Reinehr T. (Thomas)
- RidderstrÄle M. (Martin)
- Ridker P.M. (Paul)
- Rij A.M. (Andre) van
- Ripatti S. (Samuli)
- Rissanen A. (Aila)
- Rivadeneira Ramirez F. (Fernando)
- Roberts R. (Robert)
- Rocheleau G. (Ghislain)
- Roden M. (Michael)
- Rosendaal F.R. (Frits R.)
- Rudan I. (Igor)
- Rudan I. (Igor)
- Rust S. (Stephan)
- Rybin D. (Denis)
- Rzehak P. (Peter)
- Sabater-Lleal M. (Maria)
- Saleheen D. (Danish)
- Salomaa V. (Veikko)
- Samad A. (Adbus)
- Samani N.J. (Nilesh)
- Samani N.J. (Nilesh)
- Sampietro M.L. (Maria Lourdes)
- Sampson M.J. (Michael)
- Samuel M. (Maria)
- Sanders A.R. (Alan R.)
- Sandholt C. (Camilla)
- Sandhu M.S. (Manjinder)
- Sandhu M.S. (Manjinder)
- Sanna S. (Serena)
- Saramies J. (Jouko)
- Savolainen M.J. (Markku)
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- Sayer A.A.
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- Schrezenmeir J. (JĂŒrgen)
- Schunkert H. (Heribert)
- Schwartz S.M. (Stephen)
- Schwarz P.E.H. (Peter)
- SchÀfer A. (Arne)
- Scott J. (James)
- Scott L.J. (Laura)
- Scott L.J. (Laura)
- Seedorf U. (Udo)
- SegrĂš A.V. (Ayellet)
- Sehmi J.S. (Joban)
- Sekowska M. (Magdalena)
- Sennblad B. (Bengt)
- Serrano-RĂos M. (Manuel)
- Shah N. (Nisha)
- Shi J. (Jianxin)
- Shi J. (Jianxin)
- Shields B.M. (Beverley)
- Shields B.M. (Beverley)
- Shrader P. (Peter)
- Shuldiner A.R. (Alan)
- Shuldiner A.R. (Alan)
- Sigurdsson G. (Gunnar)
- Sijbrands E. (Eric)
- Sijbrands E.J.G. (Eric)
- Silander K. (Kaisa)
- Sinisalo J. (Juha)
- Siscovick D.S. (David)
- Sivapalaratnam S. (Suthesh)
- Sladek R. (Rob)
- Sleight P. (Peter)
- Smit J.H. (Jan)
- Smith A.V. (Albert Vernon)
- Smith A.V. (Albert)
- Smith A.V. (Davey)
- Smith T.B. (Tamara B.)
- Snoep J.D. (Jaapjan)
- Soranzo N. (Nicole)
- SparsĂž T. (Thomas)
- Spector T.D. (Timothy)
- Speliotes E.K. (Elizabeth)
- Spertus J.A. (John)
- StanÄcĂĄkovĂĄ A. (Alena)
- Stark K. (Klaus)
- Stein L.D. (Lincoln)
- Steinthorsdottir V. (Valgerdur)
- Stephens J. (Jonathan)
- Stewart A.F. (Alexandre F.)
- Stirrups K. (Kathy)
- Stoll M. (Monika)
- Strachan D.P. (David)
- Strassburger K. (Klaus)
- Strawbridge R.J. (Rona)
- Strawbridge R.J. (Rona)
- Stringham H.M. (Heather)
- Stumvoll M. (Michael)
- Sun Q. (Qi)
- Surdulescu G. (Gabriela)
- Swift A.J. (Amy)
- SyvÀnen A.C.
- Tammesoo M.L.
- Taneera J. (Jalal)
- Tang W. (W.)
- Tardif J.-C. (Jean-Claude)
- Tennstedt S. (Stephanie)
- Teslovich T.M. (Tanya M.)
- Thiering E. (Eelisabeth)
- Thiering E. (Elisabeth)
- Thompson J.R. (John)
- Thomson B. (Brian)
- Thorand B. (Barbara)
- Thorand B. (Barbara)
- Thorgeirsson G. (Gudmundur)
- Thorleifsson G. (Gudmar)
- Thorsteinsdottir U. (Unnur)
- Tichet J. (Jean)
- Timpson N.J. (Nicholas)
- Tognoni G.
- Tomaszewski M. (Maciej)
- Travers M.E. (Mary E.)
- Travers M.E. (Mary)
- Tuomi T. (Tiinamaija)
- Tuomilehto J. (Jaakko)
- Turrini F. (Fabiola)
- Tyrer J.P. (Jonathan)
- Tönjes A. (Anke)
- Uda M. (Manuela)
- Uitterlinden A.G. (André)
- Valle T.T. (Timo T.)
- Van Dam R.M. (Rob M.)
- van't Hooft F. (Ferdinand)
- Van't Hooft F. (Ferdinand)
- Vatin V. (Vincent)
- Vedantam S. (Sailaja)
- Visscher P.M. (Peter M.)
- Visscher P.M. (Peter)
- Vitart V. (Veronique)
- Vliet-Ostaptchouk J.V. (Jana) van
- Voight B.F. (Benjamin)
- Wabitsch M. (Martin)
- Waeber G. (GĂ©rard)
- Waite L. (Lindsay)
- Walker M. (Mark)
- Wallaschofski H. (Henri)
- Walters G.B. (Bragi)
- Wareham N.J. (Nicholas J.)
- Wareham N.J. (Nick)
- Watanabe R.M. (Richard)
- Watkins H. (Hugh)
- Weedon M.N. (Michael)
- Weedon M.N. (Michael)
- Welch R. (Ryan)
- Welch R.P. (Ryan)
- Wells G.A. (George)
- Weyant R.J. (Robert)
- Wheeler E. (Eleanor)
- White C.C. (Charles)
- Wichmann H.-E. (H-Erich)
- Wichmann H.E. (Heinz Erich)
- Widen E. (Elisabeth)
- Wiegand S. (Susanna)
- Wijmenga C. (Cisca)
- Wiklund F. (Fredrik)
- Wild P.S. (Philipp)
- Wild S.H. (Sarah)
- Wilk A. (Alicja)
- Willemsen G.A.H.M. (Gonneke)
- Willenborg C. (Christina)
- Willer C.J. (Cristen)
- Wilson J.F. (James F.)
- Wingerden S. (Sophie) van
- Winkler T.W. (Thomas W.)
- Witte D.R. (Daniel R.)
- Witte D.R. (Deniel)
- Witteman J. (Jacqueline)
- Witteman J.C.M. (Jacqueline)
- Witteman J.C.M. (Jaqueline C.M.)
- Wood A.R. (Andrew)
- Workalemahu T. (Tsegaselassie)
- Wright A.F. (Alan)
- Wright B.J. (Benjamin)
- Wu G. (Guanming)
- Xie W. (Weijia)
- Xu J. (Jianfeng)
- Yang J. (Jian)
- Yang J. (Joanna)
- Yang T.-P. (Tsun-Po)
- Ye S. (Shu)
- Zabena C. (Carina)
- Zaidi M.A. (Aghar)
- Zaman K.S. (Khan Shah)
- Zeggini E. (Eleftheria)
- Zeller T. (Tanja)
- Zethelius B. (Björn)
- Zgaga L. (Lina)
- Zhang Q. (Qunyuan)
- Zhang W. (Weihua)
- Zhao J.H. (Jing Hua)
- Ziegler A. (Andreas)
- Ziegler A. (Andreas)
- Zillikens M.C. (Carola)
- Zitting P. (Paavo)
- Zondervan K.T. (Krina T.)
- Zondervan K.T. (Krina)
- Zwart J-A. (John-Anker)
- Ăhrvik J. (John)
- Ăstenson C.-G. (Claes-Göran)
- Publication venue
- Publication date
- 01/10/2011
- Field of study
OBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS - Nine SNPs at eight loci were associated with proinsulin levels (P < 5 Ă 10-8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/ C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 3 10-4), improved b-cell function (P = 1.1 Ă 10-5), and lower risk of T2D (odds ratio 0.88; P = 7.8 Ă 10-6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS - We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis