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IRIS
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 (β=-0.09±0.01 mmol l(-1), P=3.4 × 10(-12)), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035 pmolinsulin mmolglucose(-1), P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l(-1), P=4.3 × 10(-4)). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 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 (β=0.02±0.004 mmol l(-1), P=1.3 × 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility / Wessel, Jennifer; Chu, Audrey Y; Willems, Sara M; Wang, Shuai; Yaghootkar, Hanieh; Brody, Jennifer A; Dauriz, Marco; Hivert, Marie France; Raghavan, Sridharan; Lipovich, Leonard; Hidalgo, Bertha; Fox, Keolu; Huffman, Jennifer E; An, Ping; Lu, Yingchang; Rasmussen Torvik, Laura J; Grarup, Niels; Ehm, Margaret G; Li, Li; Baldridge, Abigail S; Stančáková, Alena; Abrol, Ravinder; Besse, Céline; Boland, Anne; Bork Jensen, Jette; Fornage, Myriam; Freitag, Daniel F; Garcia, Melissa E; Guo, Xiuqing; Hara, Kazuo; Isaacs, Aaron; Jakobsdottir, Johanna; Lange, Leslie A; Layton, Jill C; Li, Man; Hua Zhao, Jing; Meidtner, Karina; Morrison, Alanna C; Nalls, Mike A; Peters, Marjolein J; Sabater Lleal, Maria; Schurmann, Claudia; Silveira, Angela; Smith, Albert V; Southam, Lorraine; Stoiber, Marcus H; Strawbridge, Rona J; Taylor, Kent D; Varga, Tibor V; Allin, Kristine H; Amin, Najaf; Aponte, Jennifer L; Aung, Tin; Barbieri, Caterina; Bihlmeyer, Nathan A; Boehnke, Michael; Bombieri, Cristina; Bowden, Donald W; Burns, Sean M; Chen, Yuning; Chen, Yii DerI; Cheng, Ching Yu; Correa, Adolfo; Czajkowski, Jacek; Dehghan, Abbas; Ehret, Georg B; Eiriksdottir, Gudny; Escher, Stefan A; Farmaki, Aliki Eleni; Frånberg, Mattias; Gambaro, Giovanni; Giulianini, Franco; Goddard, William A; Goel, Anuj; Gottesman, Omri; Grove, Megan L; Gustafsson, Stefan; Hai, Yang; Hallmans, Göran; Heo, Jiyoung; Hoffmann, Per; Ikram, Mohammad K; Jensen, Richard A; Jørgensen, Marit E; Jørgensen, Torben; Karaleftheri, Maria; Khor, Chiea C; Kirkpatrick, Andrea; Kraja, Aldi T; Kuusisto, Johanna; Lange, Ethan M; Lee, I. T; Lee, Wen Jane; Leong, Aaron; Liao, Jiemin; Liu, Chunyu; Liu, Yongmei; Lindgren, Cecilia M; Linneberg, Allan; Malerba, Giovanni; Mamakou, Vasiliki; Marouli, Eirini; Maruthur, Nisa M; Matchan, Angela; McKean Cowdin, Roberta; Mcleod, Olga; Metcalf, Ginger A; Mohlke, Karen L; Muzny, Donna M; Ntalla, Ioanna; Palmer, Nicholette D; Pasko, Dorota; Peter, Andreas; Rayner, Nigel W; Renström, Frida; Rice, Ken; Sala, Cinzia F; Sennblad, Bengt; Serafetinidis, Ioannis; Smith, Jennifer A; Soranzo, Nicole; Speliotes, Elizabeth K; Stahl, Eli A; Stirrups, Kathleen; Tentolouris, Nikos; Thanopoulou, Anastasia; Torres, Mina; Traglia, Michela; Tsafantakis, Emmanouil; Javad, Sundas; Yanek, Lisa R; Zengini, Eleni; Becker, Diane M; Bis, Joshua C; Brown, James B; Cupples, L. Adrienne; Hansen, Torben; Ingelsson, Erik; Karter, Andrew J; Lorenzo, Carlos; Mathias, Rasika A; Norris, Jill M; Peloso, Gina M; Sheu, Wayne H. H; Toniolo, Daniela; Vaidya, Dhananjay; Varma, Rohit; Wagenknecht, Lynne E; Boeing, Heiner; Bottinger, Erwin P; Dedoussis, George; Deloukas, Panos; Ferrannini, Ele; Franco, Oscar H; Franks, Paul W; Gibbs, Richard A; Gudnason, Vilmundur; Hamsten, Anders; Harris, Tamara B; Hattersley, Andrew T; Hayward, Caroline; Hofman, Albert; Jansson, Jan Håkan; Langenberg, Claudia; Launer, Lenore J; Levy, Daniel; Oostra, Ben A; O'Donnell, Christopher J; O'Rahilly, Stephen; Padmanabhan, Sandosh; Pankow, James S; Polasek, Ozren; Province, Michael A; Rich, Stephen S; Ridker, Paul M; Rudan, Igor; Schulze, Matthias B; Smith, Blair H; Uitterlinden, André G; Walker, Mark; Watkins, Hugh; Wong, Tien Y; Zeggini, Eleftheria; Laakso, Markku; Borecki, Ingrid B; Chasman, Daniel I; Pedersen, Oluf; Psaty, Bruce M; Tai, E. Shyong; van Duijn, Cornelia M; Wareham, Nicholas J; Waterworth, Dawn M; Boerwinkle, Eric; Kao, W. H. Linda; Florez, Jose C; Loos, Ruth J. F; Wilson, James G; Frayling, Timothy M; Siscovick, David S; Dupuis, Josée; Rotter, Jerome I; Meigs, James B; Scott, Robert A; Goodarzi, Mark O.; Panico, Salvatore. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 6:(2015), p. 5897. [10.1038/ncomms6897]
Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
Wessel, Jennifer;Chu, Audrey Y;Willems, Sara M;Wang, Shuai;Yaghootkar, Hanieh;Brody, Jennifer A;Dauriz, Marco;Hivert, Marie France;Raghavan, Sridharan;Lipovich, Leonard;Hidalgo, Bertha;Fox, Keolu;Huffman, Jennifer E;An, Ping;Lu, Yingchang;Rasmussen Torvik, Laura J;Grarup, Niels;Ehm, Margaret G;Li, Li;Baldridge, Abigail S;Stančáková, Alena;Abrol, Ravinder;Besse, Céline;Boland, Anne;Bork Jensen, Jette;Fornage, Myriam;Freitag, Daniel F;Garcia, Melissa E;Guo, Xiuqing;Hara, Kazuo;Isaacs, Aaron;Jakobsdottir, Johanna;Lange, Leslie A;Layton, Jill C;Li, Man;Hua Zhao, Jing;Meidtner, Karina;Morrison, Alanna C;Nalls, Mike A;Peters, Marjolein J;Sabater Lleal, Maria;Schurmann, Claudia;Silveira, Angela;Smith, Albert V;Southam, Lorraine;Stoiber, Marcus H;Strawbridge, Rona J;Taylor, Kent D;Varga, Tibor V;Allin, Kristine H;Amin, Najaf;Aponte, Jennifer L;Aung, Tin;Barbieri, Caterina;Bihlmeyer, Nathan A;Boehnke, Michael;Bombieri, Cristina;Bowden, Donald W;Burns, Sean M;Chen, Yuning;Chen, Yii DerI;Cheng, Ching Yu;Correa, Adolfo;Czajkowski, Jacek;Dehghan, Abbas;Ehret, Georg B;Eiriksdottir, Gudny;Escher, Stefan A;Farmaki, Aliki Eleni;Frånberg, Mattias;Gambaro, Giovanni;Giulianini, Franco;Goddard, William A;Goel, Anuj;Gottesman, Omri;Grove, Megan L;Gustafsson, Stefan;Hai, Yang;Hallmans, Göran;Heo, Jiyoung;Hoffmann, Per;Ikram, Mohammad K;Jensen, Richard A;Jørgensen, Marit E;Jørgensen, Torben;Karaleftheri, Maria;Khor, Chiea C;Kirkpatrick, Andrea;Kraja, Aldi T;Kuusisto, Johanna;Lange, Ethan M;Lee, I. T;Lee, Wen Jane;Leong, Aaron;Liao, Jiemin;Liu, Chunyu;Liu, Yongmei;Lindgren, Cecilia M;Linneberg, Allan;Malerba, Giovanni;Mamakou, Vasiliki;Marouli, Eirini;Maruthur, Nisa M;Matchan, Angela;McKean Cowdin, Roberta;Mcleod, Olga;Metcalf, Ginger A;Mohlke, Karen L;Muzny, Donna M;Ntalla, Ioanna;Palmer, Nicholette D;Pasko, Dorota;Peter, Andreas;Rayner, Nigel W;Renström, Frida;Rice, Ken;Sala, Cinzia F;Sennblad, Bengt;Serafetinidis, Ioannis;Smith, Jennifer A;Soranzo, Nicole;Speliotes, Elizabeth K;Stahl, Eli A;Stirrups, Kathleen;Tentolouris, Nikos;Thanopoulou, Anastasia;Torres, Mina;Traglia, Michela;Tsafantakis, Emmanouil;Javad, Sundas;Yanek, Lisa R;Zengini, Eleni;Becker, Diane M;Bis, Joshua C;Brown, James B;Cupples, L. Adrienne;Hansen, Torben;Ingelsson, Erik;Karter, Andrew J;Lorenzo, Carlos;Mathias, Rasika A;Norris, Jill M;Peloso, Gina M;Sheu, Wayne H. H;Toniolo, Daniela;Vaidya, Dhananjay;Varma, Rohit;Wagenknecht, Lynne E;Boeing, Heiner;Bottinger, Erwin P;Dedoussis, George;Deloukas, Panos;Ferrannini, Ele;Franco, Oscar H;Franks, Paul W;Gibbs, Richard A;Gudnason, Vilmundur;Hamsten, Anders;Harris, Tamara B;Hattersley, Andrew T;Hayward, Caroline;Hofman, Albert;Jansson, Jan Håkan;Langenberg, Claudia;Launer, Lenore J;Levy, Daniel;Oostra, Ben A;O'Donnell, Christopher J;O'Rahilly, Stephen;Padmanabhan, Sandosh;Pankow, James S;Polasek, Ozren;Province, Michael A;Rich, Stephen S;Ridker, Paul M;Rudan, Igor;Schulze, Matthias B;Smith, Blair H;Uitterlinden, André G;Walker, Mark;Watkins, Hugh;Wong, Tien Y;Zeggini, Eleftheria;Laakso, Markku;Borecki, Ingrid B;Chasman, Daniel I;Pedersen, Oluf;Psaty, Bruce M;Tai, E. Shyong;van Duijn, Cornelia M;Wareham, Nicholas J;Waterworth, Dawn M;Boerwinkle, Eric;Kao, W. H. Linda;Florez, Jose C;Loos, Ruth J. F;Wilson, James G;Frayling, Timothy M;Siscovick, David S;Dupuis, Josée;Rotter, Jerome I;Meigs, James B;Scott, Robert A;Goodarzi, Mark O.;PANICO, SALVATORE
2015
Abstract
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 (β=-0.09±0.01 mmol l(-1), P=3.4 × 10(-12)), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035 pmolinsulin mmolglucose(-1), P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l(-1), P=4.3 × 10(-4)). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 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 (β=0.02±0.004 mmol l(-1), P=1.3 × 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility / Wessel, Jennifer; Chu, Audrey Y; Willems, Sara M; Wang, Shuai; Yaghootkar, Hanieh; Brody, Jennifer A; Dauriz, Marco; Hivert, Marie France; Raghavan, Sridharan; Lipovich, Leonard; Hidalgo, Bertha; Fox, Keolu; Huffman, Jennifer E; An, Ping; Lu, Yingchang; Rasmussen Torvik, Laura J; Grarup, Niels; Ehm, Margaret G; Li, Li; Baldridge, Abigail S; Stančáková, Alena; Abrol, Ravinder; Besse, Céline; Boland, Anne; Bork Jensen, Jette; Fornage, Myriam; Freitag, Daniel F; Garcia, Melissa E; Guo, Xiuqing; Hara, Kazuo; Isaacs, Aaron; Jakobsdottir, Johanna; Lange, Leslie A; Layton, Jill C; Li, Man; Hua Zhao, Jing; Meidtner, Karina; Morrison, Alanna C; Nalls, Mike A; Peters, Marjolein J; Sabater Lleal, Maria; Schurmann, Claudia; Silveira, Angela; Smith, Albert V; Southam, Lorraine; Stoiber, Marcus H; Strawbridge, Rona J; Taylor, Kent D; Varga, Tibor V; Allin, Kristine H; Amin, Najaf; Aponte, Jennifer L; Aung, Tin; Barbieri, Caterina; Bihlmeyer, Nathan A; Boehnke, Michael; Bombieri, Cristina; Bowden, Donald W; Burns, Sean M; Chen, Yuning; Chen, Yii DerI; Cheng, Ching Yu; Correa, Adolfo; Czajkowski, Jacek; Dehghan, Abbas; Ehret, Georg B; Eiriksdottir, Gudny; Escher, Stefan A; Farmaki, Aliki Eleni; Frånberg, Mattias; Gambaro, Giovanni; Giulianini, Franco; Goddard, William A; Goel, Anuj; Gottesman, Omri; Grove, Megan L; Gustafsson, Stefan; Hai, Yang; Hallmans, Göran; Heo, Jiyoung; Hoffmann, Per; Ikram, Mohammad K; Jensen, Richard A; Jørgensen, Marit E; Jørgensen, Torben; Karaleftheri, Maria; Khor, Chiea C; Kirkpatrick, Andrea; Kraja, Aldi T; Kuusisto, Johanna; Lange, Ethan M; Lee, I. T; Lee, Wen Jane; Leong, Aaron; Liao, Jiemin; Liu, Chunyu; Liu, Yongmei; Lindgren, Cecilia M; Linneberg, Allan; Malerba, Giovanni; Mamakou, Vasiliki; Marouli, Eirini; Maruthur, Nisa M; Matchan, Angela; McKean Cowdin, Roberta; Mcleod, Olga; Metcalf, Ginger A; Mohlke, Karen L; Muzny, Donna M; Ntalla, Ioanna; Palmer, Nicholette D; Pasko, Dorota; Peter, Andreas; Rayner, Nigel W; Renström, Frida; Rice, Ken; Sala, Cinzia F; Sennblad, Bengt; Serafetinidis, Ioannis; Smith, Jennifer A; Soranzo, Nicole; Speliotes, Elizabeth K; Stahl, Eli A; Stirrups, Kathleen; Tentolouris, Nikos; Thanopoulou, Anastasia; Torres, Mina; Traglia, Michela; Tsafantakis, Emmanouil; Javad, Sundas; Yanek, Lisa R; Zengini, Eleni; Becker, Diane M; Bis, Joshua C; Brown, James B; Cupples, L. Adrienne; Hansen, Torben; Ingelsson, Erik; Karter, Andrew J; Lorenzo, Carlos; Mathias, Rasika A; Norris, Jill M; Peloso, Gina M; Sheu, Wayne H. H; Toniolo, Daniela; Vaidya, Dhananjay; Varma, Rohit; Wagenknecht, Lynne E; Boeing, Heiner; Bottinger, Erwin P; Dedoussis, George; Deloukas, Panos; Ferrannini, Ele; Franco, Oscar H; Franks, Paul W; Gibbs, Richard A; Gudnason, Vilmundur; Hamsten, Anders; Harris, Tamara B; Hattersley, Andrew T; Hayward, Caroline; Hofman, Albert; Jansson, Jan Håkan; Langenberg, Claudia; Launer, Lenore J; Levy, Daniel; Oostra, Ben A; O'Donnell, Christopher J; O'Rahilly, Stephen; Padmanabhan, Sandosh; Pankow, James S; Polasek, Ozren; Province, Michael A; Rich, Stephen S; Ridker, Paul M; Rudan, Igor; Schulze, Matthias B; Smith, Blair H; Uitterlinden, André G; Walker, Mark; Watkins, Hugh; Wong, Tien Y; Zeggini, Eleftheria; Laakso, Markku; Borecki, Ingrid B; Chasman, Daniel I; Pedersen, Oluf; Psaty, Bruce M; Tai, E. Shyong; van Duijn, Cornelia M; Wareham, Nicholas J; Waterworth, Dawn M; Boerwinkle, Eric; Kao, W. H. Linda; Florez, Jose C; Loos, Ruth J. F; Wilson, James G; Frayling, Timothy M; Siscovick, David S; Dupuis, Josée; Rotter, Jerome I; Meigs, James B; Scott, Robert A; Goodarzi, Mark O.; Panico, Salvatore. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 6:(2015), p. 5897. [10.1038/ncomms6897]
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.