Standard
A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease. / Scott, Robert A.; Freitag, Daniel F.; Li, Li; Chu, Audrey Y.; Surendran, Praveen; Young, Robin; Grarup, Niels; Stancakova, Alena; Chen, Yuning; Varga, Tibor V.; Yaghootkar, Hanieh; Luan, Jian'an; Zhao, Jing Hua; Willems, Sara M.; Wessel, Jennifer; Wang, Shuai; Maruthur, Nisa; Michailidou, Kyriaki; Pirie, Ailith; van der Lee, Sven J.; Gillson, Christopher; Al Olama, Ali Amin; Amouyel, Philippe; Arriola, Larraitz; Arveiler, Dominique; Aviles-Olmos, Iciar; Balkau, Beverley; Barricarte, Aurelio; Barroso, Ines; Garcia, Sara Benlloch; Bis, Joshua C.; Blankenberg, Stefan; Boehnke, Michael; Boeing, Heiner; Boerwinkle, Eric; Borecki, Ingrid B.; Bork-Jensen, Jette; Bowden, Sarah; Caldas, Carlos; Caslake, Muriel; Cupples, L. Adrienne; Cruchaga, Carlos; Czajkowski, Jacek; den Hoed, Marcel; Dunn, Janet A.; Earl, Helena M.; Ehret, Georg B.; Ferrannini, Ele; Ferrieres, Jean; Foltynie, Thomas; Ford, Ian; Forouhi, Nita G.; Gianfagna, Francesco; Gonzalez, Carlos; Grioni, Sara; Hiller, Louise; Jansson, Jan-Hakan; Jørgensen, Marit E.; Jukema, J. Wouter; Kaaks, Rudolf; Kee, Frank; Kerrison, Nicola D.; Key, Timothy J.; Kontto, Jukka; Kote-Jarai, Zsofia; Kraja, Aldi T.; Kuulasmaa, Kari; Kuusisto, Johanna; Linneberg, Allan; Liu, Chunyu; Marenne, Galle; Mohlke, Karen L.; Morris, Andrew P.; Muir, Kenneth; Mueller-Nurasyid, Martina; Munroe, Patricia B.; Navarro, Carmen; Nielsen, Sune F.; Nilsson, Peter M.; Nordestgaard, Borge G.; Packard, Chris J.; Palli, Domenico; Panico, Salvatore; Peloso, Gina M.; Perola, Markus; Peters, Annette; Poole, Christopher J.; Quiros, J. Ramn; Rolandsson, Olov; Sacerdote, Carlotta; Salomaa, Veikko; Sanchez, Mara-Jose; Sattar, Naveed; Sharp, Stephen J.; Sims, Rebecca; Slimani, Nadia; Smith, Jennifer A.; Thompson, Deborah J.; Trompet, Stella; Tumino, Rosario; van der A, Daphne L.; van der Schouw, Yvonne T.; Virtamo, Jarmo; Walker, Mark; Walter, Klaudia; Abraham, Jean E.; Amundadottir, Laufey T.; Aponte, Jennifer L.; Butterworth, Adams.; Dupuis, Josee; Easton, Douglas F.; Eeles, Rosalind A.; Erdmann, Jeanette; Franks, Paul W.; Frayling, Timothy M.; Hansen, Torben; Howson, Joanna M. M.; Jørgensen, Torben; Kooner, Jaspal; Laakso, Markku; Langenberg, Claudia; McCarthy, Mark I.; Pankow, James S.; Pedersen, Oluf; Riboli, Elio; Rotter, Jerome I.; Saleheen, Danish; Samani, Nilesh J.; Schunkert, Heribert; Vollenweider, Peter; O'Rahilly, Stephen; Deloukas, Panos; Danesh, John; Goodarzi, Mark O.; Kathiresan, Sekar; Meigs, James B.; Ehm, Margaret G.; Wareham, Nicholas J.; Waterworth, Dawn M.
In:
Science Translational Medicine, Vol. 8, No. 341, 341ra76, 01.06.2016.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Scott, RA, Freitag, DF, Li, L, Chu, AY, Surendran, P, Young, R
, Grarup, N, Stancakova, A, Chen, Y, Varga, TV, Yaghootkar, H, Luan, J, Zhao, JH, Willems, SM, Wessel, J, Wang, S, Maruthur, N, Michailidou, K, Pirie, A, van der Lee, SJ, Gillson, C, Al Olama, AA, Amouyel, P, Arriola, L, Arveiler, D, Aviles-Olmos, I, Balkau, B, Barricarte, A, Barroso, I, Garcia, SB, Bis, JC, Blankenberg, S, Boehnke, M, Boeing, H, Boerwinkle, E, Borecki, IB, Bork-Jensen, J, Bowden, S, Caldas, C, Caslake, M, Cupples, LA, Cruchaga, C, Czajkowski, J, den Hoed, M, Dunn, JA, Earl, HM, Ehret, GB, Ferrannini, E, Ferrieres, J, Foltynie, T, Ford, I, Forouhi, NG, Gianfagna, F, Gonzalez, C, Grioni, S, Hiller, L, Jansson, J-H, Jørgensen, ME, Jukema, JW, Kaaks, R, Kee, F, Kerrison, ND, Key, TJ, Kontto, J, Kote-Jarai, Z, Kraja, AT, Kuulasmaa, K, Kuusisto, J
, Linneberg, A, Liu, C, Marenne, G, Mohlke, KL, Morris, AP, Muir, K, Mueller-Nurasyid, M, Munroe, PB, Navarro, C, Nielsen, SF, Nilsson, PM, Nordestgaard, BG, Packard, CJ, Palli, D, Panico, S, Peloso, GM, Perola, M, Peters, A, Poole, CJ, Quiros, JR, Rolandsson, O, Sacerdote, C, Salomaa, V, Sanchez, M-J, Sattar, N, Sharp, SJ, Sims, R, Slimani, N, Smith, JA, Thompson, DJ, Trompet, S, Tumino, R, van der A, DL, van der Schouw, YT, Virtamo, J, Walker, M, Walter, K, Abraham, JE, Amundadottir, LT, Aponte, JL, Butterworth, A, Dupuis, J, Easton, DF, Eeles, RA, Erdmann, J, Franks, PW, Frayling, TM
, Hansen, T, Howson, JMM, Jørgensen, T, Kooner, J, Laakso, M, Langenberg, C, McCarthy, MI, Pankow, JS
, Pedersen, O, Riboli, E, Rotter, JI, Saleheen, D, Samani, NJ, Schunkert, H, Vollenweider, P, O'Rahilly, S, Deloukas, P, Danesh, J, Goodarzi, MO, Kathiresan, S, Meigs, JB, Ehm, MG, Wareham, NJ & Waterworth, DM 2016, '
A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease',
Science Translational Medicine, vol. 8, no. 341, 341ra76.
https://doi.org/10.1126/scitranslmed.aad3744APA
Scott, R. A., Freitag, D. F., Li, L., Chu, A. Y., Surendran, P., Young, R.
, Grarup, N., Stancakova, A., Chen, Y., Varga, T. V., Yaghootkar, H., Luan, J., Zhao, J. H., Willems, S. M., Wessel, J., Wang, S., Maruthur, N., Michailidou, K., Pirie, A., ... Waterworth, D. M. (2016).
A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease.
Science Translational Medicine,
8(341), [341ra76].
https://doi.org/10.1126/scitranslmed.aad3744Vancouver
Scott RA, Freitag DF, Li L, Chu AY, Surendran P, Young R et al.
A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease.
Science Translational Medicine. 2016 Jun 1;8(341). 341ra76.
https://doi.org/10.1126/scitranslmed.aad3744Author
Scott, Robert A. ; Freitag, Daniel F. ; Li, Li ; Chu, Audrey Y. ; Surendran, Praveen ; Young, Robin ; Grarup, Niels ; Stancakova, Alena ; Chen, Yuning ; Varga, Tibor V. ; Yaghootkar, Hanieh ; Luan, Jian'an ; Zhao, Jing Hua ; Willems, Sara M. ; Wessel, Jennifer ; Wang, Shuai ; Maruthur, Nisa ; Michailidou, Kyriaki ; Pirie, Ailith ; van der Lee, Sven J. ; Gillson, Christopher ; Al Olama, Ali Amin ; Amouyel, Philippe ; Arriola, Larraitz ; Arveiler, Dominique ; Aviles-Olmos, Iciar ; Balkau, Beverley ; Barricarte, Aurelio ; Barroso, Ines ; Garcia, Sara Benlloch ; Bis, Joshua C. ; Blankenberg, Stefan ; Boehnke, Michael ; Boeing, Heiner ; Boerwinkle, Eric ; Borecki, Ingrid B. ; Bork-Jensen, Jette ; Bowden, Sarah ; Caldas, Carlos ; Caslake, Muriel ; Cupples, L. Adrienne ; Cruchaga, Carlos ; Czajkowski, Jacek ; den Hoed, Marcel ; Dunn, Janet A. ; Earl, Helena M. ; Ehret, Georg B. ; Ferrannini, Ele ; Ferrieres, Jean ; Foltynie, Thomas ; Ford, Ian ; Forouhi, Nita G. ; Gianfagna, Francesco ; Gonzalez, Carlos ; Grioni, Sara ; Hiller, Louise ; Jansson, Jan-Hakan ; Jørgensen, Marit E. ; Jukema, J. Wouter ; Kaaks, Rudolf ; Kee, Frank ; Kerrison, Nicola D. ; Key, Timothy J. ; Kontto, Jukka ; Kote-Jarai, Zsofia ; Kraja, Aldi T. ; Kuulasmaa, Kari ; Kuusisto, Johanna ; Linneberg, Allan ; Liu, Chunyu ; Marenne, Galle ; Mohlke, Karen L. ; Morris, Andrew P. ; Muir, Kenneth ; Mueller-Nurasyid, Martina ; Munroe, Patricia B. ; Navarro, Carmen ; Nielsen, Sune F. ; Nilsson, Peter M. ; Nordestgaard, Borge G. ; Packard, Chris J. ; Palli, Domenico ; Panico, Salvatore ; Peloso, Gina M. ; Perola, Markus ; Peters, Annette ; Poole, Christopher J. ; Quiros, J. Ramn ; Rolandsson, Olov ; Sacerdote, Carlotta ; Salomaa, Veikko ; Sanchez, Mara-Jose ; Sattar, Naveed ; Sharp, Stephen J. ; Sims, Rebecca ; Slimani, Nadia ; Smith, Jennifer A. ; Thompson, Deborah J. ; Trompet, Stella ; Tumino, Rosario ; van der A, Daphne L. ; van der Schouw, Yvonne T. ; Virtamo, Jarmo ; Walker, Mark ; Walter, Klaudia ; Abraham, Jean E. ; Amundadottir, Laufey T. ; Aponte, Jennifer L. ; Butterworth, Adams. ; Dupuis, Josee ; Easton, Douglas F. ; Eeles, Rosalind A. ; Erdmann, Jeanette ; Franks, Paul W. ; Frayling, Timothy M. ; Hansen, Torben ; Howson, Joanna M. M. ; Jørgensen, Torben ; Kooner, Jaspal ; Laakso, Markku ; Langenberg, Claudia ; McCarthy, Mark I. ; Pankow, James S. ; Pedersen, Oluf ; Riboli, Elio ; Rotter, Jerome I. ; Saleheen, Danish ; Samani, Nilesh J. ; Schunkert, Heribert ; Vollenweider, Peter ; O'Rahilly, Stephen ; Deloukas, Panos ; Danesh, John ; Goodarzi, Mark O. ; Kathiresan, Sekar ; Meigs, James B. ; Ehm, Margaret G. ; Wareham, Nicholas J. ; Waterworth, Dawn M. / A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease. In: Science Translational Medicine. 2016 ; Vol. 8, No. 341.
Bibtex
@article{a73ffa0b705d4d7ea2257b12a1011ac2,
title = "A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease",
abstract = "Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.",
author = "Scott, {Robert A.} and Freitag, {Daniel F.} and Li Li and Chu, {Audrey Y.} and Praveen Surendran and Robin Young and Niels Grarup and Alena Stancakova and Yuning Chen and Varga, {Tibor V.} and Hanieh Yaghootkar and Jian'an Luan and Zhao, {Jing Hua} and Willems, {Sara M.} and Jennifer Wessel and Shuai Wang and Nisa Maruthur and Kyriaki Michailidou and Ailith Pirie and {van der Lee}, {Sven J.} and Christopher Gillson and {Al Olama}, {Ali Amin} and Philippe Amouyel and Larraitz Arriola and Dominique Arveiler and Iciar Aviles-Olmos and Beverley Balkau and Aurelio Barricarte and Ines Barroso and Garcia, {Sara Benlloch} and Bis, {Joshua C.} and Stefan Blankenberg and Michael Boehnke and Heiner Boeing and Eric Boerwinkle and Borecki, {Ingrid B.} and Jette Bork-Jensen and Sarah Bowden and Carlos Caldas and Muriel Caslake and Cupples, {L. Adrienne} and Carlos Cruchaga and Jacek Czajkowski and {den Hoed}, Marcel and Dunn, {Janet A.} and Earl, {Helena M.} and Ehret, {Georg B.} and Ele Ferrannini and Jean Ferrieres and Thomas Foltynie and Ian Ford and Forouhi, {Nita G.} and Francesco Gianfagna and Carlos Gonzalez and Sara Grioni and Louise Hiller and Jan-Hakan Jansson and J{\o}rgensen, {Marit E.} and Jukema, {J. Wouter} and Rudolf Kaaks and Frank Kee and Kerrison, {Nicola D.} and Key, {Timothy J.} and Jukka Kontto and Zsofia Kote-Jarai and Kraja, {Aldi T.} and Kari Kuulasmaa and Johanna Kuusisto and Allan Linneberg and Chunyu Liu and Galle Marenne and Mohlke, {Karen L.} and Morris, {Andrew P.} and Kenneth Muir and Martina Mueller-Nurasyid and Munroe, {Patricia B.} and Carmen Navarro and Nielsen, {Sune F.} and Nilsson, {Peter M.} and Nordestgaard, {Borge G.} and Packard, {Chris J.} and Domenico Palli and Salvatore Panico and Peloso, {Gina M.} and Markus Perola and Annette Peters and Poole, {Christopher J.} and Quiros, {J. Ramn} and Olov Rolandsson and Carlotta Sacerdote and Veikko Salomaa and Mara-Jose Sanchez and Naveed Sattar and Sharp, {Stephen J.} and Rebecca Sims and Nadia Slimani and Smith, {Jennifer A.} and Thompson, {Deborah J.} and Stella Trompet and Rosario Tumino and {van der A}, {Daphne L.} and {van der Schouw}, {Yvonne T.} and Jarmo Virtamo and Mark Walker and Klaudia Walter and Abraham, {Jean E.} and Amundadottir, {Laufey T.} and Aponte, {Jennifer L.} and Adams. Butterworth and Josee Dupuis and Easton, {Douglas F.} and Eeles, {Rosalind A.} and Jeanette Erdmann and Franks, {Paul W.} and Frayling, {Timothy M.} and Torben Hansen and Howson, {Joanna M. M.} and Torben J{\o}rgensen and Jaspal Kooner and Markku Laakso and Claudia Langenberg and McCarthy, {Mark I.} and Pankow, {James S.} and Oluf Pedersen and Elio Riboli and Rotter, {Jerome I.} and Danish Saleheen and Samani, {Nilesh J.} and Heribert Schunkert and Peter Vollenweider and Stephen O'Rahilly and Panos Deloukas and John Danesh and Goodarzi, {Mark O.} and Sekar Kathiresan and Meigs, {James B.} and Ehm, {Margaret G.} and Wareham, {Nicholas J.} and Waterworth, {Dawn M.}",
year = "2016",
month = jun,
day = "1",
doi = "10.1126/scitranslmed.aad3744",
language = "English",
volume = "8",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "american association for the advancement of science",
number = "341",
}
RIS
TY - JOUR
T1 - A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
AU - Scott, Robert A.
AU - Freitag, Daniel F.
AU - Li, Li
AU - Chu, Audrey Y.
AU - Surendran, Praveen
AU - Young, Robin
AU - Grarup, Niels
AU - Stancakova, Alena
AU - Chen, Yuning
AU - Varga, Tibor V.
AU - Yaghootkar, Hanieh
AU - Luan, Jian'an
AU - Zhao, Jing Hua
AU - Willems, Sara M.
AU - Wessel, Jennifer
AU - Wang, Shuai
AU - Maruthur, Nisa
AU - Michailidou, Kyriaki
AU - Pirie, Ailith
AU - van der Lee, Sven J.
AU - Gillson, Christopher
AU - Al Olama, Ali Amin
AU - Amouyel, Philippe
AU - Arriola, Larraitz
AU - Arveiler, Dominique
AU - Aviles-Olmos, Iciar
AU - Balkau, Beverley
AU - Barricarte, Aurelio
AU - Barroso, Ines
AU - Garcia, Sara Benlloch
AU - Bis, Joshua C.
AU - Blankenberg, Stefan
AU - Boehnke, Michael
AU - Boeing, Heiner
AU - Boerwinkle, Eric
AU - Borecki, Ingrid B.
AU - Bork-Jensen, Jette
AU - Bowden, Sarah
AU - Caldas, Carlos
AU - Caslake, Muriel
AU - Cupples, L. Adrienne
AU - Cruchaga, Carlos
AU - Czajkowski, Jacek
AU - den Hoed, Marcel
AU - Dunn, Janet A.
AU - Earl, Helena M.
AU - Ehret, Georg B.
AU - Ferrannini, Ele
AU - Ferrieres, Jean
AU - Foltynie, Thomas
AU - Ford, Ian
AU - Forouhi, Nita G.
AU - Gianfagna, Francesco
AU - Gonzalez, Carlos
AU - Grioni, Sara
AU - Hiller, Louise
AU - Jansson, Jan-Hakan
AU - Jørgensen, Marit E.
AU - Jukema, J. Wouter
AU - Kaaks, Rudolf
AU - Kee, Frank
AU - Kerrison, Nicola D.
AU - Key, Timothy J.
AU - Kontto, Jukka
AU - Kote-Jarai, Zsofia
AU - Kraja, Aldi T.
AU - Kuulasmaa, Kari
AU - Kuusisto, Johanna
AU - Linneberg, Allan
AU - Liu, Chunyu
AU - Marenne, Galle
AU - Mohlke, Karen L.
AU - Morris, Andrew P.
AU - Muir, Kenneth
AU - Mueller-Nurasyid, Martina
AU - Munroe, Patricia B.
AU - Navarro, Carmen
AU - Nielsen, Sune F.
AU - Nilsson, Peter M.
AU - Nordestgaard, Borge G.
AU - Packard, Chris J.
AU - Palli, Domenico
AU - Panico, Salvatore
AU - Peloso, Gina M.
AU - Perola, Markus
AU - Peters, Annette
AU - Poole, Christopher J.
AU - Quiros, J. Ramn
AU - Rolandsson, Olov
AU - Sacerdote, Carlotta
AU - Salomaa, Veikko
AU - Sanchez, Mara-Jose
AU - Sattar, Naveed
AU - Sharp, Stephen J.
AU - Sims, Rebecca
AU - Slimani, Nadia
AU - Smith, Jennifer A.
AU - Thompson, Deborah J.
AU - Trompet, Stella
AU - Tumino, Rosario
AU - van der A, Daphne L.
AU - van der Schouw, Yvonne T.
AU - Virtamo, Jarmo
AU - Walker, Mark
AU - Walter, Klaudia
AU - Abraham, Jean E.
AU - Amundadottir, Laufey T.
AU - Aponte, Jennifer L.
AU - Butterworth, Adams.
AU - Dupuis, Josee
AU - Easton, Douglas F.
AU - Eeles, Rosalind A.
AU - Erdmann, Jeanette
AU - Franks, Paul W.
AU - Frayling, Timothy M.
AU - Hansen, Torben
AU - Howson, Joanna M. M.
AU - Jørgensen, Torben
AU - Kooner, Jaspal
AU - Laakso, Markku
AU - Langenberg, Claudia
AU - McCarthy, Mark I.
AU - Pankow, James S.
AU - Pedersen, Oluf
AU - Riboli, Elio
AU - Rotter, Jerome I.
AU - Saleheen, Danish
AU - Samani, Nilesh J.
AU - Schunkert, Heribert
AU - Vollenweider, Peter
AU - O'Rahilly, Stephen
AU - Deloukas, Panos
AU - Danesh, John
AU - Goodarzi, Mark O.
AU - Kathiresan, Sekar
AU - Meigs, James B.
AU - Ehm, Margaret G.
AU - Wareham, Nicholas J.
AU - Waterworth, Dawn M.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
AB - Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
U2 - 10.1126/scitranslmed.aad3744
DO - 10.1126/scitranslmed.aad3744
M3 - Journal article
C2 - 27252175
VL - 8
JO - Science Translational Medicine
JF - Science Translational Medicine
SN - 1946-6234
IS - 341
M1 - 341ra76
ER -
