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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Wessel, Jennifer (author)
Chu, Audrey Y. (author)
Willems, Sara M. (author)
show more...
Wang, Shuai (author)
Yaghootkar, Hanieh (author)
Brody, Jennifer A. (author)
Dauriz, Marco (author)
Hivert, Marie-France (author)
Raghavan, Sridharan (author)
Lipovich, Leonard (author)
Hidalgo, Bertha (author)
Fox, Keolu (author)
Huffman, Jennifer E. (author)
An, Ping (author)
Lu, Yingchang (author)
Rasmussen-Torvik, Laura J. (author)
Grarup, Niels (author)
Ehm, Margaret G. (author)
Li, Li (author)
Baldridge, Abigail S. (author)
Stancakova, Alena (author)
Abrol, Ravinder (author)
Besse, Celine (author)
Boland, Anne (author)
Bork-Jensen, Jette (author)
Fornage, Myriam (author)
Freitag, Daniel F. (author)
Garcia, Melissa E. (author)
Guo, Xiuqing (author)
Hara, Kazuo (author)
Isaacs, Aaron (author)
Jakobsdottir, Johanna (author)
Lange, Leslie A. (author)
Layton, Jill C. (author)
Li, Man (author)
Zhao, Jing Hua (author)
Meidtner, Karina (author)
Morrison, Alanna C. (author)
Nalls, Mike A. (author)
Peters, Marjolein J. (author)
Sabater-Lleal, Maria (author)
Schurmann, Claudia (author)
Silveira, Angela (author)
Smith, Albert V. (author)
Southam, Lorraine (author)
Stoiber, Marcus H. (author)
Strawbridge, Rona J. (author)
Taylor, Kent D. (author)
Varga, Tibor V. (author)
Allin, Kristine H. (author)
Amin, Najaf (author)
Aponte, Jennifer L. (author)
Aung, Tin (author)
Barbieri, Caterina (author)
Bihlmeyer, Nathan A. (author)
Boehnke, Michael (author)
Bombieri, Cristina (author)
Bowden, Donald W. (author)
Burns, Sean M. (author)
Chen, Yuning (author)
Chen, Yii-Deri (author)
Cheng, Ching-Yu (author)
Correa, Adolfo (author)
Czajkowski, Jacek (author)
Dehghan, Abbas (author)
Ehret, Georg B. (author)
Eiriksdottir, Gudny (author)
Andersson Escher, Stefan (author)
Farmaki, Aliki-Eleni (author)
Franberg, Mattias (author)
Gambaro, Giovanni (author)
Giulianini, Franco (author)
Goddard, William A., III (author)
Goel, Anuj (author)
Gottesman, Omri (author)
Grove, Megan L. (author)
Gustafsson, Stefan (author)
Hai, Yang (author)
Hallmans, Goeran (author)
Heo, Jiyoung (author)
Hoffmann, Per (author)
Ikram, Mohammad K. (author)
Jensen, Richard A. (author)
Jorgensen, Marit E. (author)
Jorgensen, Torben (author)
Karaleftheri, Maria (author)
Khor, Chiea C. (author)
Kirkpatrick, Andrea (author)
Kraja, Aldi T. (author)
Kuusisto, Johanna (author)
Lange, Ethan M. (author)
Lee, I. T. (author)
Lee, Wen-Jane (author)
Leong, Aaron (author)
Liao, Jiemin (author)
Liu, Chunyu (author)
Liu, Yongmei (author)
Lindgren, Cecilia M. (author)
Linneberg, Allan (author)
Malerba, Giovanni (author)
Mamakou, Vasiliki (author)
Marouli, Eirini (author)
Maruthur, Nisa M. (author)
Matchan, Angela (author)
McKean-Cowdin, Roberta (author)
McLeod, Olga (author)
Metcalf, Ginger A. (author)
Mohlke, Karen L. (author)
Muzny, Donna M. (author)
Ntalla, Ioanna (author)
Palmer, Nicholette D. (author)
Pasko, Dorota (author)
Peter, Andreas (author)
Rayner, Nigel W. (author)
Renstroem, Frida (author)
Rice, Ken (author)
Sala, Cinzia F. (author)
Sennblad, Bengt (author)
Serafetinidis, Ioannis (author)
Smith, Jennifer A. (author)
Soranzo, Nicole (author)
Speliotes, Elizabeth K. (author)
Stahl, Eli A. (author)
Stirrups, Kathleen (author)
Tentolouris, Nikos (author)
Thanopoulou, Anastasia (author)
Torres, Mina (author)
Traglia, Michela (author)
Tsafantakis, Emmanouil (author)
Javad, Sundas (author)
Yanek, Lisa R. (author)
Zengini, Eleni (author)
Becker, Diane M. (author)
Bis, Joshua C. (author)
Brown, James B. (author)
Cupples, L. Adrienne (author)
Hansen, Torben (author)
Ingelsson, Erik (author)
Karter, Andrew J. (author)
Lorenzo, Carlos (author)
Mathias, Rasika A. (author)
Norris, Jill M. (author)
Peloso, Gina M. (author)
Sheu, Wayne H. -H. (author)
Toniolo, Daniela (author)
Vaidya, Dhananjay (author)
Varma, Rohit (author)
Wagenknecht, Lynne E. (author)
Boeing, Heiner (author)
Bottinger, Erwin P. (author)
Dedoussis, George (author)
Deloukas, Panos (author)
Ferrannini, Ele (author)
Franco, Oscar H. (author)
Franks, Paul W. (author)
Gibbs, Richard A. (author)
Gudnason, Vilmundur (author)
Hamsten, Anders (author)
Harris, Tamara B. (author)
Hattersley, Andrew T. (author)
Hayward, Caroline (author)
Hofman, Albert (author)
Jansson, Jan-Håkan (author)
Langenberg, Claudia (author)
Launer, Lenore J. (author)
Levy, Daniel (author)
Oostra, Ben A. (author)
O'Donnell, Christopher J. (author)
O'Rahilly, Stephen (author)
Padmanabhan, Sandosh (author)
Pankow, James S. (author)
Polasek, Ozren (author)
Province, Michael A. (author)
Rich, Stephen S. (author)
Ridker, Paul M. (author)
Rudan, Igor (author)
Schulze, Matthias B. (author)
Smith, Blair H. (author)
Uitterlinden, Andre G. (author)
Walker, Mark (author)
Watkins, Hugh (author)
Wong, Tien Y. (author)
Zeggini, Eleftheria (author)
Laakso, Markku (author)
Borecki, Ingrid B. (author)
Chasman, Daniel I. (author)
Pedersen, Oluf (author)
Psaty, Bruce M. (author)
Tai, E. Shyong (author)
van Duijn, Cornelia M. (author)
Wareham, Nicholas J. (author)
Waterworth, Dawn M. (author)
Boerwinkle, Eric (author)
Kao, W. H. Linda (author)
Florez, Jose C. (author)
Loos, Ruth J. F. (author)
Wilson, James G. (author)
Frayling, Timothy M. (author)
Siscovick, David S. (author)
Dupuis, Josee (author)
Rotter, Jerome I. (author)
Meigs, James B. (author)
Scott, Robert A. (author)
Goodarzi, Mark O. (author)
Sharp, Stephen J. (author)
Forouhi, Nita G. (author)
Kerrison, Nicola D. (author)
Lucarelli, Debora M. E. (author)
Sims, Matt (author)
Barroso, Ines (author)
McCarthy, Mark I. (author)
Arriola, Larraitz (author)
Balkau, Beverley (author)
Barricarte, Aurelio (author)
Gonzalez, Carlos (author)
Grioni, Sara (author)
Kaaks, Rudolf (author)
Key, Timothy J. (author)
Navarro, Carmen (author)
Nilsson, Peter M. (author)
Overvad, Kim (author)
Palli, Domenico (author)
Panico, Salvatore (author)
Quiros, J. Ramon (author)
Rolandsson, Olov (author)
Sacerdote, Carlotta (author)
Sanchez, Maria-Jose (author)
Slimani, Nadia (author)
Tjonneland, Anne (author)
Tumino, Rosario (author)
van der A, Daphne L. (author)
van der Schouw, Yvonne T. (author)
Riboli, Elio (author)
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 (publisher)
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 (publisher)
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2015
2015
English.
In: Nature Communications. - 2041-1723. ; 6
  • swepub:Mat__t
Abstract Subject headings
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  • Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.

Subject headings

Medical and Health Sciences  (hsv)
Clinical Medicine  (hsv)
Endocrinology and Diabetes  (hsv)
Medicin och hälsovetenskap  (hsv)
Klinisk medicin  (hsv)
Endokrinologi och diabetes  (hsv)

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Wessel, Jennifer
Chu, Audrey Y.
Willems, Sara M.
Wang, Shuai
Yaghootkar, Hani ...
Brody, Jennifer ...
show more...
Dauriz, Marco
Hivert, Marie-Fr ...
Raghavan, Sridha ...
Lipovich, Leonar ...
Hidalgo, Bertha
Fox, Keolu
Huffman, Jennife ...
An, Ping
Lu, Yingchang
Rasmussen-Torvik ...
Grarup, Niels
Ehm, Margaret G.
Li, Li
Baldridge, Abiga ...
Stancakova, Alen ...
Abrol, Ravinder
Besse, Celine
Boland, Anne
Bork-Jensen, Jet ...
Fornage, Myriam
Freitag, Daniel ...
Garcia, Melissa ...
Guo, Xiuqing
Hara, Kazuo
Isaacs, Aaron
Jakobsdottir, Jo ...
Lange, Leslie A.
Layton, Jill C.
Li, Man
Zhao, Jing Hua
Meidtner, Karina
Morrison, Alanna ...
Nalls, Mike A.
Peters, Marjolei ...
Sabater-Lleal, M ...
Schurmann, Claud ...
Silveira, Angela
Smith, Albert V.
Southam, Lorrain ...
Stoiber, Marcus ...
Strawbridge, Ron ...
Taylor, Kent D.
Varga, Tibor V.
Allin, Kristine ...
Amin, Najaf
Aponte, Jennifer ...
Aung, Tin
Barbieri, Cateri ...
Bihlmeyer, Natha ...
Boehnke, Michael
Bombieri, Cristi ...
Bowden, Donald W ...
Burns, Sean M.
Chen, Yuning
Chen, Yii-Deri
Cheng, Ching-Yu
Correa, Adolfo
Czajkowski, Jace ...
Dehghan, Abbas
Ehret, Georg B.
Eiriksdottir, Gu ...
Andersson Escher ...
Farmaki, Aliki-E ...
Franberg, Mattia ...
Gambaro, Giovann ...
Giulianini, Fran ...
Goddard, William ...
Goel, Anuj
Gottesman, Omri
Grove, Megan L.
Gustafsson, Stef ...
Hai, Yang
Hallmans, Goeran
Heo, Jiyoung
Hoffmann, Per
Ikram, Mohammad ...
Jensen, Richard ...
Jorgensen, Marit ...
Jorgensen, Torbe ...
Karaleftheri, Ma ...
Khor, Chiea C.
Kirkpatrick, And ...
Kraja, Aldi T.
Kuusisto, Johann ...
Lange, Ethan M.
Lee, I. T.
Lee, Wen-Jane
Leong, Aaron
Liao, Jiemin
Liu, Chunyu
Liu, Yongmei
Lindgren, Cecili ...
Linneberg, Allan
Malerba, Giovann ...
Mamakou, Vasilik ...
Marouli, Eirini
Maruthur, Nisa M ...
Matchan, Angela
McKean-Cowdin, R ...
McLeod, Olga
Metcalf, Ginger ...
Mohlke, Karen L.
Muzny, Donna M.
Ntalla, Ioanna
Palmer, Nicholet ...
Pasko, Dorota
Peter, Andreas
Rayner, Nigel W.
Renstroem, Frida
Rice, Ken
Sala, Cinzia F.
Sennblad, Bengt
Serafetinidis, I ...
Smith, Jennifer ...
Soranzo, Nicole
Speliotes, Eliza ...
Stahl, Eli A.
Stirrups, Kathle ...
Tentolouris, Nik ...
Thanopoulou, Ana ...
Torres, Mina
Traglia, Michela
Tsafantakis, Emm ...
Javad, Sundas
Yanek, Lisa R.
Zengini, Eleni
Becker, Diane M.
Bis, Joshua C.
Brown, James B.
Cupples, L. Adri ...
Hansen, Torben
Ingelsson, Erik
Karter, Andrew J ...
Lorenzo, Carlos
Mathias, Rasika ...
Norris, Jill M.
Peloso, Gina M.
Sheu, Wayne H. - ...
Toniolo, Daniela
Vaidya, Dhananja ...
Varma, Rohit
Wagenknecht, Lyn ...
Boeing, Heiner
Bottinger, Erwin ...
Dedoussis, Georg ...
Deloukas, Panos
Ferrannini, Ele
Franco, Oscar H.
Franks, Paul W.
Gibbs, Richard A ...
Gudnason, Vilmun ...
Hamsten, Anders
Harris, Tamara B ...
Hattersley, Andr ...
Hayward, Carolin ...
Hofman, Albert
Jansson, Jan-Håk ...
Langenberg, Clau ...
Launer, Lenore J ...
Levy, Daniel
Oostra, Ben A.
O'Donnell, Chris ...
O'Rahilly, Steph ...
Padmanabhan, San ...
Pankow, James S.
Polasek, Ozren
Province, Michae ...
Rich, Stephen S.
Ridker, Paul M.
Rudan, Igor
Schulze, Matthia ...
Smith, Blair H.
Uitterlinden, An ...
Walker, Mark
Watkins, Hugh
Wong, Tien Y.
Zeggini, Elefthe ...
Laakso, Markku
Borecki, Ingrid ...
Chasman, Daniel ...
Pedersen, Oluf
Psaty, Bruce M.
Tai, E. Shyong
van Duijn, Corne ...
Wareham, Nichola ...
Waterworth, Dawn ...
Boerwinkle, Eric
Kao, W. H. Linda
Florez, Jose C.
Loos, Ruth J. F.
Wilson, James G.
Frayling, Timoth ...
Siscovick, David ...
Dupuis, Josee
Rotter, Jerome I ...
Meigs, James B.
Scott, Robert A.
Goodarzi, Mark O ...
Sharp, Stephen J ...
Forouhi, Nita G.
Kerrison, Nicola ...
Lucarelli, Debor ...
Sims, Matt
Barroso, Ines
McCarthy, Mark I ...
Arriola, Larrait ...
Balkau, Beverley
Barricarte, Aure ...
Gonzalez, Carlos
Grioni, Sara
Kaaks, Rudolf
Key, Timothy J.
Navarro, Carmen
Nilsson, Peter M ...
Overvad, Kim
Palli, Domenico
Panico, Salvator ...
Quiros, J. Ramon
Rolandsson, Olov
Sacerdote, Carlo ...
Sanchez, Maria-J ...
Slimani, Nadia
Tjonneland, Anne
Tumino, Rosario
van der A, Daphn ...
van der Schouw, ...
Riboli, Elio
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