3 research outputs found
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)
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- Ahmed N. (Nabeel)
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- Allen H.L.
- Almgren P. (Peter)
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- 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)
- Öhrvik J. (John)
- Östenson 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 × 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 × 10-5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 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
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.)
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- Bidulescu A. (Aurelian)
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- Rudan I. (Igor)
- Rudan I. (Igor)
- Ruokonen A. (Aimo)
- Ruokonen A. (Aimo)
- Rybin D. (Denis)
- Sabatti C. (Chiara)
- Saharinen J. (Juha)
- Salomaa V. (Veikko)
- Salomaa V. (Veikko)
- Salomaa V. (Veikko)
- Samani N.J. (Nilesh)
- Samani N.J. (Nilesh)
- Sampson M.J. (Michael J)
- Sampson M.J. (Michael)
- Sandbaek A. (Annelli)
- Sandhu M. (Manjinder)
- Sandhu M.S. (Manjinder)
- Sanna S. (Serena)
- Sanna S. (Serena)
- Sattar N. (Naveed)
- Saxena R. (Richa)
- Saxena R. (Richa)
- Sayer A.A.
- Schadt E.E. (Eric E.)
- Schadt E.E. (Eric)
- Scheet P. (Paul)
- Schlessinger D. (David)
- Schlessinger D. (David)
- Schunkert H. (Heribert)
- Schwarz P.E.H. (Peter)
- Scott L.J. (Laura J.)
- Scott L.J. (Laura)
- Scott R.A. (Robert)
- Scuteri A. (Angelo)
- Scuteri A. (Angelo)
- Scuteri A. (Angelo)
- Seedorf U. (Udo)
- Segrè A.V. (Ayellet)
- Seielstad M. (Mark)
- Semple R.K. (Robert K.)
- Serrano-Ríos M. (Manuel)
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- Sharp S.J. (Stephen)
- Shields B.M. (Beverley)
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- Shrader P. (Peter)
- Shrader P. (Peter)
- Shuldiner A.R. (Alan)
- Sigurdsson G. (Gunnar)
- Sigursson G. (Gunnar)
- Sijbrands E. (Eric)
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- Sijbrands E.J.G. (Eric)
- Silander K. (Kaisa)
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- Simpson L. (Laila)
- Singleton A. (Andrew)
- Sinisalo J. (Juha)
- Siscovick D.S. (David)
- Siscovick D.S. (David)
- Sladek R. (Rob)
- Sladek R. (Rob)
- Slagboom P.E. (Eline)
- Small K.S. (Kerrin)
- Smith A.V. (Albert Vernon)
- Smith A.V. (Albert)
- Smith A.V. (Davey)
- Smith A.V. (Davey)
- Smith G.D. (George Davey)
- Smith J.D. (Joshua D.)
- Smith N.L. (Nicholas)
- Song K. (Kijoung)
- Soranzo N. (Nicole)
- Soranzo N. (Nicole)
- Sovio U. (Ulla)
- Sparsø T. (Thomas)
- Sparsø T. (Thomas)
- Spector T.D. (Tim D.)
- Spector T.D. (Timothy D.)
- Spector T.D. (Timothy)
- Spranger J. (Joachim)
- St Pourcain B. (Beate)
- Stefansson K. (Kari)
- Stefansson K. (Kari)
- Stein L.D. (Lincoln)
- Steinthorsdottir V. (Valgerdur)
- Steinthorsdottir V. (Valgerdur)
- Strachan D.P. (David)
- Strassburger K. (Klaus)
- Stringham H.M. (Heather M.)
- Stringham H.M. (Heather M.)
- Stringham H.M. (Heather)
- Stumvoll M. (Michael)
- Stylianou I.M. (Ioannis M.)
- Stylianou I.M. (Ioannis)
- Sun Q. (Qi)
- Surakka I. (Ida)
- Swift A.J. (Amy)
- Swift A.J. (Amy)
- Syddall H. (Holly)
- Syvänen A.C.
- Tai E.-S. (E-Shyong)
- Tai E.S. (Shyong)
- Tall A.R. (Alan R.)
- Tanaka T. (Toshiko)
- Taylor H.A. (Herman A.)
- Taylor H.A. (Herman)
- Teslovich T.M. (Tanya M.)
- Teslovich T.M. (Tanya M.)
- Thompson J.R. (John)
- Thompson J.R. (John)
- Thorand B. (Barbara)
- Thorand B. (Barbara)
- Thorleifsson G. (Gudmar)
- Thorleifsson G. (Gudmar)
- Thorleifsson G. (Gudmar)
- Thorsteinsdottir U. (Unnur)
- Thorsteinsdottir U. (Unnur)
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- Thorsteinsdottir U. (Unnur)
- Tichet J. (Jean)
- Tichet J. (Jean)
- Timpson N.J. (Nicholas J.)
- Timpson N.J. (Nicholas)
- Tracy R.P. (Russell)
- Tuomi T. (Tiinamaija)
- Tuomi T. (Tiinamaija)
- Tuomilehto J. (Jaakko)
- Tuomilehto J. (Jaakko)
- Tuomilehto J. (Jaakko)
- Tönjes A. (Anke)
- Uda M. (Manuela)
- Uda M. (Manuela)
- Uh H.-W. (Hae-Won)
- Uitterlinden A. (Andre)
- Uitterlinden A.G. (Andre G.)
- Uitterlinden A.G. (André)
- Valle T.T. (Timo T.)
- van Duijn C. (Cornelia)
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- van Duijn C.M. (Cornelia M.)
- van Hoek M. (Mandy)
- Varma D. (Dhiraj)
- Viikari J. (Jorma)
- Visvikis-Siest S. (Sophie)
- Vitart V. (Veronique)
- Vitart V. (Veronique)
- Vliet-Ostaptchouk J.V. (Jana) van
- 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. (Gérard)
- Waeber G. (Gérard)
- Wagner P.J. (Peter)
- Walker M. (Mark)
- Walley A. (Andrew)
- Walters G. (GBragi)
- Walters G.B. (Bragi)
- Ward K.L. (Kim L.)
- Wareham N.J. (Nick J.)
- Wareham N.J. (Nick)
- Wareham N.J. (Nick)
- Watanabe R.M. (Richard M.)
- Watanabe R.M. (Richard)
- Waterworth D. (Dawn)
- Waterworth D. (Dawn)
- Waterworth D.M. (Dawn)
- Watkins H. (Hugh)
- Weedon M.N. (Michael)
- Weedon M.N. (Michael)
- Welch R.P. (Ryan)
- Wheeler E. (Eleanor)
- Whitfield J. (John)
- Wichmann H.-E. (H.-Erich)
- Wichmann H.E. (H. Erich)
- Wichmann H.E. (Heinz Erich)
- Wichmann H.E. (Heinz Erich)
- Wijmenga C. (Cisca)
- 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)
- Ódonnell 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 = 4.5×10−8- 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
Abdominal Aortic Aneurysm Is Associated with a Variant in Low-Density Lipoprotein Receptor-Related Protein 1
- Author
- Abecasis G.R. (Gonçalo R.)
- Abecasis Gonçalo
- Absher D. (Devin)
- Adrienne Cupples L.
- Aherrahrou Zouhair
- Allayee Hooman
- Allione Alessandra
- Altshuler David
- Altshuler David
- Altshuler David
- Amin Najaf
- Anand Sonia
- Andersen Karl
- Anderson J.L. (Jeffrey L.)
- Angelica Merlini Pier
- Ardissino Diego
- Ardlie Kristin
- Assimes T.L. (Themistocles L.)
- Assimes Themistocles
- Aulchenko Yurii
- Baas Annette
- Badger Jonathan
- Balkau Beverley
- Ball Stephen
- Balmforth Anthony
- Bandinelli Stefania
- Barbalic maja
- Barnes Timothy
- Barroso Inês
- Barroso Inês
- Becker Diane
- Becker Lewis
- Beckmann Jacques
- Benediktsson Rafn
- Bengtsson Boström Kristina
- Bennett Amanda
- Berger Klaus
- Berglund G.
- Bergman R.N. (Richard N.)
- Bergman Richard N.
- Bergmann S. (Sven)
- Bingham Sheila
- Bis Joshua
- Blagieva Roza
- Blair R.D. (Ross D.)
- Blankenberg Stefan
- Blankensteijn Jan
- Bochud Murielle
- Bockxmeer Frank
- Boehm Bernhard
- Boehnke Michael
- Boehnke Michael
- Boekholdt Matthijs
- Boerwinkle E. (Eric)
- Boerwinkle Eric
- Bonnycastle L.L. (Lori L.)
- Bonnycastle Lori
- Bots Michiel
- Bown N.
- Bradley Declan
- Bragi Walters G.
- Braund Peter
- Bravenboer Bert
- Brown M.J. (Morris J.)
- Brown Morris
- Bumpstead Suzannah
- Bumpstead Suzannah
- Burnand Kevin
- Burton Paul
- Burtt Noël
- Buysschaert Ian
- Cambien François
- Campbell Harry
- Carlquist John
- Cauchi Stephane
- Caulfield Mark
- Chambers John
- Charpentier Guillaume
- Chen L. (Li)
- Child Anne
- Chines Peter
- Cichon Sven
- Clarke Robert
- Clough Rachel
- Cockerill Gillian
- Codd Veryan
- Coin L. (Lachlan)
- Collins F.S. (Francis S.)
- Collins Francis
- Connell John
- Cornelis Marilyn
- Couper David
- Crawford G.J. (Gabriel J.)
- Crawford Gabe
- Daly Mark
- Dam Rob
- Davies Robert
- de Jong P.E. (Paul E.)
- Dedoussis George
- Dehghan Abbas
- Deloukas P. (Panos)
- Deloukas P. (Panos)
- Deloukas Panagiotis
- Demissie Serkalem
- Devaney Joseph
- Di Gregorio Alessandra
- Diemert Patrick
- Dina Christian
- Do Ron
- Doering Angela
- Dominiczak Anna
- Doney Alex
- Duijn Cornelia
- Dupuis Josée
- Döring Angela
- Dörr Marcus
- Edkins Ted
- Eifert Sandra
- El Mokhtari Nour Eddine
- Elliott Amanda
- Elliott K.S. (Katherine S.)
- Elliott Katherine
- Elliott P. (Paul)
- Ellis Stephen
- Elosua R. (Roberto)
- Elosua Roberto
- Engert J.C. (James C.)
- Epstein Stephen
- Erdmann Jeanette
- Erdos Michael
- Eriksson Per
- Ernst F. (Florian)
- Eyheramendy Susana
- Faire Ulf
- Farrall Martin
- Felix Stephan
- Ferreira Teresa
- Ferrucci Luigi
- Fischer M. (Marcus)
- Florez J.C. (Jose C.)
- Folkersen Lasse
- Folsom Aaron
- Forouhi Nita
- Fox Caroline
- Franco-Cereceda Anders
- Franklin Christopher
- Frayling Timothy
- Freimer Nelson B.
- Freyer Jennifer
- Frikke-Schmidt Ruth
- Froguel Philippe
- Futers Simon
- Galan Pilar
- Ganser Martha
- Gateva Vesela
- Gerry Hill B.
- Gieger C. (Christian)
- Gieger C. (Christian)
- Gieger Christian
- Gigante Bruna
- Gilst Wiek
- Girelli Domenico
- Gloyn Anna
- Goel A. (Anuj)
- Golledge Jonathan
- Goodall Alison
- Graaf Jacqueline
- Grallert Harald
- Grarup Niels
- Green T. (Todd)
- Gretarsdottir S. (Solveig)
- Gretarsdottir Solveig
- Griffin Simon
- Grobbee Diederick
- Groop Leif
- Groop Leif
- Groves Christopher
- Guarrera Simonetta
- Gudnason Vilmundur
- Guiducci Candace
- Gulcher Jeffrey
- Gut Ivo
- Gwilliam Rhian
- Gyllensten U. (Ulf)
- Hadjadj Samy
- Hadley D. (David)
- Haeften Timon
- Hafez Hany
- Hall Alistair
- Halperin Eran
- Hammond Naomi
- Hamsten Anders
- Hansen T. (Torben)
- Harrison Seamus
- Harst Pim
- Hartikainen A.L.
- Hassanali Neelam
- Hattersley Andrew
- Hazen Stanley
- Heath Simon
- Hengstenberg Christian
- Hercberg Serge
- Herder Christian
- Herpt Thijs
- Hide Winston
- Hill A.A. (Andrew A.)
- Hitman Graham
- Hoek Mandy
- Hofman A. (Albert)
- Hofman Albert
- Hofmann Oliver
- Holm Hilma
- Homuth Georg
- Horne Benjamin
- Hu Frank
- Hua Zhao J. (Jing)
- Hughes Anne
- Humphries Steve
- Hunt Sarah
- Hunter D.J. (David J.)
- Huth Cornelia
- Hveem Kristian
- Illig Thomas
- Illig Thomas
- Illig Thomas
- Iribarren Carlos
- Isomaa Bo
- Jackson Anne
- Jackson Anne
- Jarvelin Marjo-Riitta
- Johnson A. (Anne)
- Johnson P.R.V. (Paul R. V.)
- Johnson Toby
- Jones G.T. (Gregory T.)
- Jones Gregory
- Jorgensen Torben
- Jousilahti Pekka
- Jukema Jan Wouter
- Kaiser Michael
- Kao Wen
- Kaplan Lee
- Kastelein John
- Kathiresan S. (Sekar)
- Kathiresan S. (Sekar)
- Khaw K.T.
- Khaw Kay-Tee
- Kiemeney Bart
- Klopp Norman
- Knowles Joshua
- Kolovou G. (Genovefa)
- Kong Augustine
- Kong Augustine
- Kooner Jaspal S.
- Kraft Peter
- Kuusisto Johanna
- König Inke
- Laakso M. (Markku)
- Laakso Markku
- Laaksonen Reijo
- Laan Maris
- Lakatta Edward
- Lambrechts Diether
- Langenberg Claudia
- Lathrop Mark
- Lauritzen Torsten
- Leander Karin
- Lettre Guillaume
- Lewis David
- Li Man
- Li X.
- Lieb Wolfgang
- Lieverse Aloysius
- Lim Noha
- Lindgren Cecilia
- Lindholt Jes
- Loley Christina
- Loos Ruth
- Lorbeer Roberto
- Lotery Andrew
- Lourdes Sampietro M.
- Luan J.
- Luben Robert
- Lucas G. (Gavin)
- Lyssenko Valeriya
- Mannucci Pier
- Maouche Seraya
- Marre Michel
- Marrugat Jaume
- Martinelli Nicola
- Matthiasson S.E. (Stefan E.)
- Matullo G.
- McArdle Wendy
- McCarroll Steve
- McCarthy Mark
- McCarthy Mark I.
- McCulloch Laura
- McKeown Pascal
- McNoe Les
- McPherson R. (Ruth)
- McPherson Ruth
- Meigs James
- Meisinger Christa
- Meitinger T. (Thomas)
- Meitinger T. (Thomas)
- Meitinger Thomas
- Melander O. (Olle)
- Melander Olle
- Meneton Pierre
- Merriman T.R. (Tony R.)
- Midthjell Kristian
- Mohlke Karen
- Mohlke Karen L.
- Mooser V. (Vincent)
- Mooser Vincent
- Morgan Thomas
- Morken M.A. (Mario A.)
- Morken Mario
- Morris Andrew
- Morris Andrew
- Muhlestein Joseph
- Munroe Patricia
- Munzel Thomas
- Musunuru Kiran
- März Winfried
- Mühleisen Thomas
- Nahrstaedt Janja
- Naik D.K. (Dilip K.)
- Najjar Samer
- Narisu Narisu
- Navarro Pau
- Navis Gerjan
- Nelson Christopher P.
- Newhouse Stephen
- Newton-Cheh Christopher
- Nilsson P. (Peter)
- Nilsson P. (Peter)
- Norman Paul E.
- Numans Mattijs
- Nöthen Markus
- O'Donnell Christopher
- O'Donnell Christopher J.
- O'Reilly Paul
- Olivieri O. (Oliviero)
- Onland-Moret N.C. (N. Charlotte)
- Org Elin
- Orho-Melander Marju
- Ouwehand Willem
- Owen Katharine
- Palmen Jutta
- Palmer Colin
- Panico Salvatore
- Pankow James
- Papadakis K. (Konstantinos)
- Patel Riyaz
- Patterson Chris
- Payne Felicity
- Peden John
- Pedersen Oluf
- Peltonen Leena Johanna
- Perola Markus
- Perry John
- Peters Annette
- Petersen A.K.
- Peyvandi Flora
- Pfeufer Arne
- Platou Carl
- Polidoro Silvia
- Potter Simon
- Pouta Anneli
- Powell Janet
- Pramstaller Peter Paul
- Preuss Michael
- Proença Christine
- Prokopenko Inga
- Qi Lu
- Qu Liming
- Quertermous Thomas
- Quyyumi Arshed
- Rader Daniel
- Rallidis Loukianos
- Rathmann Wolfgang
- Raychaudhuri Soumya
- Rayner Nigel William
- Reffelmann Thorsten
- Refstrup Mette
- Reilly M.P. (Muredach P.)
- Rettig Rainer
- Ricceri Fulvio
- Rice Catherine
- Rij Andre
- Roberts Robert
- Robertson Neil
- Rocheleau Ghislain
- Roden Michael
- Romanazzi Valeria
- Rosendaal Frits
- Rubin Diana
- Rudan Igor
- Sacerdote Carlotta
- Salomaa Veikko
- Salomaa Veikko
- Samani N.J. (Nilesh J.)
- Samani Nilesh
- Samani Nilesh
- Sampson M.J. (Michael J.)
- Sandhu Manjinder
- Sandhu Manjinder
- Sanna Serena
- Saxena Richa
- Sayers Ian
- Schadt Eric
- Scheet Paul
- Schillert Arne
- Schlessinger D. (David)
- Schouw Yvonne
- Schreiber S. (Stefan)
- Schrezenmeir J. (Jürgen)
- Schunkert Heribert
- Schwartz S.M. (Stephen M.)
- Schwartz S.M. (Stephen M.)
- Schäfer A. (Arne)
- Scott D Julian
- Scott L.J. (Laura J.)
- Scott Laura
- Scuteri Angelo
- Seedorf U. (Udo)
- Segrè Ayellet
- Shields Beverley
- Shrader Peter
- Sigurdsson G. (Gunnar)
- Sijbrands Eric
- Siscovick D.S. (David S.)
- Siscovick David
- Sivananthan Mohan
- Sivapalaratnam Suthesh
- Sladek Rob
- Smith A. (Alberto)
- Smith A.J.P.
- Smith Albert Vernon
- Smith T.B. (Tamara B.)
- Snieder Harold
- Snoep Jaapjan
- Sohrabi Soroush
- Song Kijoung
- Soranzo N. (Nicole)
- Soranzo Nicole
- Sparsø Thomas
- Spector Timothy
- Spertus John
- Stark K. (Klaus)
- Stefansson K. (Kari)
- Stefansson K. (Kari)
- Stein Lincoln
- Steinthorsdottir Valgerdur
- Stewart Alexandre F.
- Stirrups Kathy
- Stoll Monika
- Strachan David
- Strassburger Klaus
- Stringham H.M. (Heather M.)
- Stringham Heather
- Subirana Isaac
- Sun Qi
- Susan Burnett Mary
- Swift Amy
- Sylvius Nicolas
- Syvänen A.C.
- Tanaka Toshiko
- Tang W.
- Teijink J. A W
- Tennstedt Stephanie
- Teumer Alexander
- Thompson John
- Thompson John
- Thompson Matthew
- Thomson I.A. (Ian A.)
- Thorand Barbara
- Thorgeirsson Gudmundur
- Thorleifsson G. (Gudmar)
- Thorleifsson G. (Gudmar)
- Thorleifsson Gudmar
- Thorsteinsdottir U. (Unnur)
- Thorsteinsdottir U. (Unnur)
- Thorsteinsdottir Unnur
- Tichet Jean
- Tobin Martin
- Tognoni G. (Giovanni)
- Tomaszewski Maciej
- Topless Ruth
- Tuomi Tiinamaija
- Tuomilehto Jaakko
- Tuomilehto Jaakko
- Tybjaerg-Hansen A.
- Uda Manuela
- Uiterwaal Cuno
- Uitterlinden A. (Andre)
- Uitterlinden André
- Valle T.T. (Timo T.)
- van Rij A. (Andre)
- Vasudevan Thodur
- Vicky Phillips L.
- Vineis Paolo
- Vliet-Ostaptchouk Jana
- Voight B.F. (Benjamin F.)
- Voight B.F. (Benjamin F.)
- Voight Benjamin
- Vollenweider Peter
- Völker Uwe
- Völzke Henry
- Waeber Gérard
- Wain Louise
- Walker M. (Mark)
- Wallace Chris
- Waltham Matthew
- Wareham N.J. (Nicholas J.)
- Wareham Nick
- Wareham Nick
- Watanabe R.M. (Richard M.)
- Waterworth Dawn
- Watkins Hugh
- Webster J. (John)
- Weedon Michael
- Welch Ryan
- Wells George
- Wichmann H.E. (H. Erich)
- Wichmann Heinz Erich
- Wichmann Heinz Erich
- Wijmenga C. (Cisca)
- Wijmenga Cisca
- Wild John
- Wild Philipp
- Willenborg Christina
- Willer C.J. (Cristen J.)
- Willer Cristen
- Williams Frances
- Wilson J.F. (James F.)
- Witteman J. (Jacqueline)
- Witteman Jacqueline
- Wright Benjamin
- Wright Benjamin
- Wu Guanming
- Ye S. (Shu)
- Yu Grace
- Yuan Xin
- Zeggini Eleftheria
- Zeggini Eleftheria
- Zelenika Diana
- Zeller Tanja
- Zhai Guangju
- Zhang Feng
- Ziegler A. (Andreas)
- Zwart John-Anker
- Publication venue
- Elsevier
- Publication date
- 01/01/2011
- Field of study
Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10−5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10−5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10−10, odds ratio 1.15 [1.10–1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04–1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression