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Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci. / Walford, Geoffrey A; Gustafsson, Stefan; Rybin, Denis; Stančáková, Alena; Chen, Han; Liu, Ching-Ti; Hong, Jaeyoung; Jensen, Richard A; Rice, Ken; Morris, Andrew P; Mägi, Reedik; Tönjes, Anke; Prokopenko, Inga; Kleber, Marcus E; Delgado, Graciela; Silbernagel, Günther; Jackson, Anne U; Appel, Emil V; Grarup, Niels; Lewis, Joshua P; Montasser, May E; Landenvall, Claes; Staiger, Harald; Luan, Jian'an; Frayling, Timothy M; Weedon, Michael N; Xie, Weijia; Morcillo, Sonsoles; Martínez-Larrad, María Teresa; Biggs, Mary L; Ida Chen, Yii-Der; Corbaton-Anchuelo, Arturo; Faerch, Kristine; Zumaquero, Juan Miguel; Goodarzi, Mark O; Kizer, Jorge; Koistinen, Heikki A; Leong, Aaron; Lind, Lars; Lindgren, Cecilia; Machicao, Fausto; Manning, Alisa K; Martín-Núñez, Gracia María; Rojo-Martínez, Gemma; Rotter, Jerome I; Siscovick, David S; Zmuda, Joseph M; Zhang, Zhongyang; Serrano-Rios, Manuel; Smith, Ulf; Soriguer, Federico; Hansen, Torben; Jørgensen, Torben; Linnenberg, Allan; Pedersen, Oluf; Walker, Mark; Langenberg, Claudia; Scott, Robert A; Wareham, Nicholas J; Fritsche, Andreas; Häring, Hans-Ulrich; Stefan, Norbert; Groop, Leif; O'Connell, Jeff R; Boehnke, Michael; Bergman, Richard N; Collins, Francis S; Mohlke, Karen L; Tuomilehto, Jaakko; März, Winfried; Kovacs, Peter; Stumvoll, Michael; Psaty, Bruce M; Kuusisto, Johanna; Laakso, Markku; Meigs, James B; Dupuis, Josée; Ingelsson, Erik; Florez, Jose C.
In:
Diabetes, Vol. 65, No. 10, 10.2016, p. 3200-3211.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Walford, GA, Gustafsson, S, Rybin, D, Stančáková, A, Chen, H, Liu, C-T, Hong, J, Jensen, RA, Rice, K, Morris, AP, Mägi, R, Tönjes, A, Prokopenko, I, Kleber, ME, Delgado, G, Silbernagel, G, Jackson, AU, Appel, EV
, Grarup, N, Lewis, JP, Montasser, ME, Landenvall, C, Staiger, H, Luan, J, Frayling, TM, Weedon, MN, Xie, W, Morcillo, S, Martínez-Larrad, MT, Biggs, ML, Ida Chen, Y-D, Corbaton-Anchuelo, A, Faerch, K, Zumaquero, JM, Goodarzi, MO, Kizer, J, Koistinen, HA, Leong, A, Lind, L, Lindgren, C, Machicao, F, Manning, AK, Martín-Núñez, GM, Rojo-Martínez, G, Rotter, JI, Siscovick, DS, Zmuda, JM, Zhang, Z, Serrano-Rios, M, Smith, U, Soriguer, F
, Hansen, T, Jørgensen, T, Linnenberg, A
, Pedersen, O, Walker, M, Langenberg, C, Scott, RA, Wareham, NJ, Fritsche, A, Häring, H-U, Stefan, N, Groop, L, O'Connell, JR, Boehnke, M, Bergman, RN, Collins, FS, Mohlke, KL, Tuomilehto, J, März, W, Kovacs, P, Stumvoll, M, Psaty, BM, Kuusisto, J, Laakso, M, Meigs, JB, Dupuis, J, Ingelsson, E & Florez, JC 2016, '
Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci',
Diabetes, vol. 65, no. 10, pp. 3200-3211.
https://doi.org/10.2337/db16-0199APA
Walford, G. A., Gustafsson, S., Rybin, D., Stančáková, A., Chen, H., Liu, C-T., Hong, J., Jensen, R. A., Rice, K., Morris, A. P., Mägi, R., Tönjes, A., Prokopenko, I., Kleber, M. E., Delgado, G., Silbernagel, G., Jackson, A. U., Appel, E. V.
, Grarup, N., ... Florez, J. C. (2016).
Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci.
Diabetes,
65(10), 3200-3211.
https://doi.org/10.2337/db16-0199Vancouver
Walford GA, Gustafsson S, Rybin D, Stančáková A, Chen H, Liu C-T et al.
Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci.
Diabetes. 2016 Oct;65(10):3200-3211.
https://doi.org/10.2337/db16-0199Author
Walford, Geoffrey A ; Gustafsson, Stefan ; Rybin, Denis ; Stančáková, Alena ; Chen, Han ; Liu, Ching-Ti ; Hong, Jaeyoung ; Jensen, Richard A ; Rice, Ken ; Morris, Andrew P ; Mägi, Reedik ; Tönjes, Anke ; Prokopenko, Inga ; Kleber, Marcus E ; Delgado, Graciela ; Silbernagel, Günther ; Jackson, Anne U ; Appel, Emil V ; Grarup, Niels ; Lewis, Joshua P ; Montasser, May E ; Landenvall, Claes ; Staiger, Harald ; Luan, Jian'an ; Frayling, Timothy M ; Weedon, Michael N ; Xie, Weijia ; Morcillo, Sonsoles ; Martínez-Larrad, María Teresa ; Biggs, Mary L ; Ida Chen, Yii-Der ; Corbaton-Anchuelo, Arturo ; Faerch, Kristine ; Zumaquero, Juan Miguel ; Goodarzi, Mark O ; Kizer, Jorge ; Koistinen, Heikki A ; Leong, Aaron ; Lind, Lars ; Lindgren, Cecilia ; Machicao, Fausto ; Manning, Alisa K ; Martín-Núñez, Gracia María ; Rojo-Martínez, Gemma ; Rotter, Jerome I ; Siscovick, David S ; Zmuda, Joseph M ; Zhang, Zhongyang ; Serrano-Rios, Manuel ; Smith, Ulf ; Soriguer, Federico ; Hansen, Torben ; Jørgensen, Torben ; Linnenberg, Allan ; Pedersen, Oluf ; Walker, Mark ; Langenberg, Claudia ; Scott, Robert A ; Wareham, Nicholas J ; Fritsche, Andreas ; Häring, Hans-Ulrich ; Stefan, Norbert ; Groop, Leif ; O'Connell, Jeff R ; Boehnke, Michael ; Bergman, Richard N ; Collins, Francis S ; Mohlke, Karen L ; Tuomilehto, Jaakko ; März, Winfried ; Kovacs, Peter ; Stumvoll, Michael ; Psaty, Bruce M ; Kuusisto, Johanna ; Laakso, Markku ; Meigs, James B ; Dupuis, Josée ; Ingelsson, Erik ; Florez, Jose C. / Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci. In: Diabetes. 2016 ; Vol. 65, No. 10. pp. 3200-3211.
Bibtex
@article{7c8c656acfbb485689007fdfe005c9df,
title = "Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci",
abstract = "Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-related traits Consortium. Discovery was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, body mass index (BMI) and in a model ({"}Model 3{"}) analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI. In Model 3, three variants reached genome-wide significance: rs13422522 (NYAP2, P=8.87 ×10(-11)), rs12454712 (BCL2, P=2.7×10(-8)) and rs10506418 (FAM19A2, P=1.9×10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardio-metabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.",
author = "Walford, {Geoffrey A} and Stefan Gustafsson and Denis Rybin and Alena Stan{\v c}{\'a}kov{\'a} and Han Chen and Ching-Ti Liu and Jaeyoung Hong and Jensen, {Richard A} and Ken Rice and Morris, {Andrew P} and Reedik M{\"a}gi and Anke T{\"o}njes and Inga Prokopenko and Kleber, {Marcus E} and Graciela Delgado and G{\"u}nther Silbernagel and Jackson, {Anne U} and Appel, {Emil V} and Niels Grarup and Lewis, {Joshua P} and Montasser, {May E} and Claes Landenvall and Harald Staiger and Jian'an Luan and Frayling, {Timothy M} and Weedon, {Michael N} and Weijia Xie and Sonsoles Morcillo and Mart{\'i}nez-Larrad, {Mar{\'i}a Teresa} and Biggs, {Mary L} and {Ida Chen}, Yii-Der and Arturo Corbaton-Anchuelo and Kristine Faerch and Zumaquero, {Juan Miguel} and Goodarzi, {Mark O} and Jorge Kizer and Koistinen, {Heikki A} and Aaron Leong and Lars Lind and Cecilia Lindgren and Fausto Machicao and Manning, {Alisa K} and Mart{\'i}n-N{\'u}{\~n}ez, {Gracia Mar{\'i}a} and Gemma Rojo-Mart{\'i}nez and Rotter, {Jerome I} and Siscovick, {David S} and Zmuda, {Joseph M} and Zhongyang Zhang and Manuel Serrano-Rios and Ulf Smith and Federico Soriguer and Torben Hansen and Torben J{\o}rgensen and Allan Linnenberg and Oluf Pedersen and Mark Walker and Claudia Langenberg and Scott, {Robert A} and Wareham, {Nicholas J} and Andreas Fritsche and Hans-Ulrich H{\"a}ring and Norbert Stefan and Leif Groop and O'Connell, {Jeff R} and Michael Boehnke and Bergman, {Richard N} and Collins, {Francis S} and Mohlke, {Karen L} and Jaakko Tuomilehto and Winfried M{\"a}rz and Peter Kovacs and Michael Stumvoll and Psaty, {Bruce M} and Johanna Kuusisto and Markku Laakso and Meigs, {James B} and Jos{\'e}e Dupuis and Erik Ingelsson and Florez, {Jose C}",
note = "{\textcopyright} 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.",
year = "2016",
month = oct,
doi = "10.2337/db16-0199",
language = "English",
volume = "65",
pages = "3200--3211",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "10",
}
RIS
TY - JOUR
T1 - Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci
AU - Walford, Geoffrey A
AU - Gustafsson, Stefan
AU - Rybin, Denis
AU - Stančáková, Alena
AU - Chen, Han
AU - Liu, Ching-Ti
AU - Hong, Jaeyoung
AU - Jensen, Richard A
AU - Rice, Ken
AU - Morris, Andrew P
AU - Mägi, Reedik
AU - Tönjes, Anke
AU - Prokopenko, Inga
AU - Kleber, Marcus E
AU - Delgado, Graciela
AU - Silbernagel, Günther
AU - Jackson, Anne U
AU - Appel, Emil V
AU - Grarup, Niels
AU - Lewis, Joshua P
AU - Montasser, May E
AU - Landenvall, Claes
AU - Staiger, Harald
AU - Luan, Jian'an
AU - Frayling, Timothy M
AU - Weedon, Michael N
AU - Xie, Weijia
AU - Morcillo, Sonsoles
AU - Martínez-Larrad, María Teresa
AU - Biggs, Mary L
AU - Ida Chen, Yii-Der
AU - Corbaton-Anchuelo, Arturo
AU - Faerch, Kristine
AU - Zumaquero, Juan Miguel
AU - Goodarzi, Mark O
AU - Kizer, Jorge
AU - Koistinen, Heikki A
AU - Leong, Aaron
AU - Lind, Lars
AU - Lindgren, Cecilia
AU - Machicao, Fausto
AU - Manning, Alisa K
AU - Martín-Núñez, Gracia María
AU - Rojo-Martínez, Gemma
AU - Rotter, Jerome I
AU - Siscovick, David S
AU - Zmuda, Joseph M
AU - Zhang, Zhongyang
AU - Serrano-Rios, Manuel
AU - Smith, Ulf
AU - Soriguer, Federico
AU - Hansen, Torben
AU - Jørgensen, Torben
AU - Linnenberg, Allan
AU - Pedersen, Oluf
AU - Walker, Mark
AU - Langenberg, Claudia
AU - Scott, Robert A
AU - Wareham, Nicholas J
AU - Fritsche, Andreas
AU - Häring, Hans-Ulrich
AU - Stefan, Norbert
AU - Groop, Leif
AU - O'Connell, Jeff R
AU - Boehnke, Michael
AU - Bergman, Richard N
AU - Collins, Francis S
AU - Mohlke, Karen L
AU - Tuomilehto, Jaakko
AU - März, Winfried
AU - Kovacs, Peter
AU - Stumvoll, Michael
AU - Psaty, Bruce M
AU - Kuusisto, Johanna
AU - Laakso, Markku
AU - Meigs, James B
AU - Dupuis, Josée
AU - Ingelsson, Erik
AU - Florez, Jose C
N1 - © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
PY - 2016/10
Y1 - 2016/10
N2 - Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-related traits Consortium. Discovery was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, body mass index (BMI) and in a model ("Model 3") analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI. In Model 3, three variants reached genome-wide significance: rs13422522 (NYAP2, P=8.87 ×10(-11)), rs12454712 (BCL2, P=2.7×10(-8)) and rs10506418 (FAM19A2, P=1.9×10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardio-metabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.
AB - Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-related traits Consortium. Discovery was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, body mass index (BMI) and in a model ("Model 3") analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI. In Model 3, three variants reached genome-wide significance: rs13422522 (NYAP2, P=8.87 ×10(-11)), rs12454712 (BCL2, P=2.7×10(-8)) and rs10506418 (FAM19A2, P=1.9×10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardio-metabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.
U2 - 10.2337/db16-0199
DO - 10.2337/db16-0199
M3 - Journal article
C2 - 27416945
VL - 65
SP - 3200
EP - 3211
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 10
ER -
