Genome-wide Association Study of Change in Fasting Glucose over time in 13,807 non-diabetic European Ancestry Individuals

Ching Ti Liu; Jordi Merino; Denis Rybin; Daniel DiCorpo; Kelly S. Benke; Jennifer L. Bragg-Gresham; Mickaël Canouil; Tanguy Corre; Harald Grallert; Aaron Isaacs; Zoltan Kutalik; Jari Lahti; Letizia Marullo; Carola Marzi; Laura J. Rasmussen-Torvik; Ghislain Rocheleau; Rico Rueedi; Chiara Scapoli; Niek Verweij; Nicole Vogelzangs; Sara M. Willems; Loïc Yengo; Stephan J.L. Bakker; John Beilby; Jennie Hui; Eero Kajantie; Martina Müller-Nurasyid; Wolfgang Rathmann; Beverley Balkau; Sven Bergmann; Johan G. Eriksson; Jose C. Florez; Philippe Froguel; Tamara Harris; Joseph Hung; Alan L. James; Maryam Kavousi; Iva Miljkovic; Arthur W. Musk; Lyle J. Palmer; Annette Peters; Ronan Roussel; Pim van der harst; Cornelia M. van Duijn; Peter Vollenweider; Inês Barroso; Inga Prokopenko; Josée Dupuis; James B. Meigs; Nabila Bouatia-Naji

doi:10.1038/s41598-019-45823-7

Genome-wide Association Study of Change in Fasting Glucose over time in 13,807 non-diabetic European Ancestry Individuals

Ching Ti Liu, Jordi Merino, Denis Rybin, Daniel DiCorpo, Kelly S. Benke, Jennifer L. Bragg-Gresham, Mickaël Canouil, Tanguy Corre, Harald Grallert, Aaron Isaacs, Zoltan Kutalik, Jari Lahti, Letizia Marullo, Carola Marzi, Laura J. Rasmussen-Torvik, Ghislain Rocheleau, Rico Rueedi, Chiara Scapoli, Niek Verweij, Nicole VogelzangsSara M. Willems, Loïc Yengo, Stephan J.L. Bakker, John Beilby, Jennie Hui, Eero Kajantie, Martina Müller-Nurasyid, Wolfgang Rathmann, Beverley Balkau, Sven Bergmann, Johan G. Eriksson, Jose C. Florez, Philippe Froguel, Tamara Harris, Joseph Hung, Alan L. James, Maryam Kavousi, Iva Miljkovic, Arthur W. Musk, Lyle J. Palmer, Annette Peters, Ronan Roussel, Pim van der harst, Cornelia M. van Duijn, Peter Vollenweider, Inês Barroso, Inga Prokopenko, Josée Dupuis, James B. Meigs, Nabila Bouatia-Naji

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Abstract

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 × 10⁻⁸) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.

Original language	English
Article number	9439
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-45823-7
State	Published - 1 Dec 2019

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Liu, C. T., Merino, J., Rybin, D., DiCorpo, D., Benke, K. S., Bragg-Gresham, J. L., Canouil, M., Corre, T., Grallert, H., Isaacs, A., Kutalik, Z., Lahti, J., Marullo, L., Marzi, C., Rasmussen-Torvik, L. J., Rocheleau, G., Rueedi, R., Scapoli, C., Verweij, N., ... Bouatia-Naji, N. (2019). Genome-wide Association Study of Change in Fasting Glucose over time in 13,807 non-diabetic European Ancestry Individuals. Scientific Reports, 9(1), Article 9439. https://doi.org/10.1038/s41598-019-45823-7

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title = "Genome-wide Association Study of Change in Fasting Glucose over time in 13,807 non-diabetic European Ancestry Individuals",

abstract = "Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 × 10−8) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.",

author = "Liu, {Ching Ti} and Jordi Merino and Denis Rybin and Daniel DiCorpo and Benke, {Kelly S.} and Bragg-Gresham, {Jennifer L.} and Micka{\"e}l Canouil and Tanguy Corre and Harald Grallert and Aaron Isaacs and Zoltan Kutalik and Jari Lahti and Letizia Marullo and Carola Marzi and Rasmussen-Torvik, {Laura J.} and Ghislain Rocheleau and Rico Rueedi and Chiara Scapoli and Niek Verweij and Nicole Vogelzangs and Willems, {Sara M.} and Lo{\"i}c Yengo and Bakker, {Stephan J.L.} and John Beilby and Jennie Hui and Eero Kajantie and Martina M{\"u}ller-Nurasyid and Wolfgang Rathmann and Beverley Balkau and Sven Bergmann and Eriksson, {Johan G.} and Florez, {Jose C.} and Philippe Froguel and Tamara Harris and Joseph Hung and James, {Alan L.} and Maryam Kavousi and Iva Miljkovic and Musk, {Arthur W.} and Palmer, {Lyle J.} and Annette Peters and Ronan Roussel and {van der harst}, Pim and {van Duijn}, {Cornelia M.} and Peter Vollenweider and In{\^e}s Barroso and Inga Prokopenko and Jos{\'e}e Dupuis and Meigs, {James B.} and Nabila Bouatia-Naji",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41598-019-45823-7",

language = "English",

volume = "9",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

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Liu, CT, Merino, J, Rybin, D, DiCorpo, D, Benke, KS, Bragg-Gresham, JL, Canouil, M, Corre, T, Grallert, H, Isaacs, A, Kutalik, Z, Lahti, J, Marullo, L, Marzi, C, Rasmussen-Torvik, LJ, Rocheleau, G, Rueedi, R, Scapoli, C, Verweij, N, Vogelzangs, N, Willems, SM, Yengo, L, Bakker, SJL, Beilby, J, Hui, J, Kajantie, E, Müller-Nurasyid, M, Rathmann, W, Balkau, B, Bergmann, S, Eriksson, JG, Florez, JC, Froguel, P, Harris, T, Hung, J, James, AL, Kavousi, M, Miljkovic, I, Musk, AW, Palmer, LJ, Peters, A, Roussel, R, van der harst, P, van Duijn, CM, Vollenweider, P, Barroso, I, Prokopenko, I, Dupuis, J, Meigs, JB & Bouatia-Naji, N 2019, 'Genome-wide Association Study of Change in Fasting Glucose over time in 13,807 non-diabetic European Ancestry Individuals', Scientific Reports, vol. 9, no. 1, 9439. https://doi.org/10.1038/s41598-019-45823-7

TY - JOUR

T1 - Genome-wide Association Study of Change in Fasting Glucose over time in 13,807 non-diabetic European Ancestry Individuals

AU - Liu, Ching Ti

AU - Merino, Jordi

AU - Rybin, Denis

AU - DiCorpo, Daniel

AU - Benke, Kelly S.

AU - Bragg-Gresham, Jennifer L.

AU - Canouil, Mickaël

AU - Corre, Tanguy

AU - Grallert, Harald

AU - Isaacs, Aaron

AU - Kutalik, Zoltan

AU - Lahti, Jari

AU - Marullo, Letizia

AU - Marzi, Carola

AU - Rasmussen-Torvik, Laura J.

AU - Rocheleau, Ghislain

AU - Rueedi, Rico

AU - Scapoli, Chiara

AU - Verweij, Niek

AU - Vogelzangs, Nicole

AU - Willems, Sara M.

AU - Yengo, Loïc

AU - Bakker, Stephan J.L.

AU - Beilby, John

AU - Hui, Jennie

AU - Kajantie, Eero

AU - Müller-Nurasyid, Martina

AU - Rathmann, Wolfgang

AU - Balkau, Beverley

AU - Bergmann, Sven

AU - Eriksson, Johan G.

AU - Florez, Jose C.

AU - Froguel, Philippe

AU - Harris, Tamara

AU - Hung, Joseph

AU - James, Alan L.

AU - Kavousi, Maryam

AU - Miljkovic, Iva

AU - Musk, Arthur W.

AU - Palmer, Lyle J.

AU - Peters, Annette

AU - Roussel, Ronan

AU - van der harst, Pim

AU - van Duijn, Cornelia M.

AU - Vollenweider, Peter

AU - Barroso, Inês

AU - Prokopenko, Inga

AU - Dupuis, Josée

AU - Meigs, James B.

AU - Bouatia-Naji, Nabila

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 × 10−8) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.

AB - Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 × 10−8) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.

UR - http://www.scopus.com/inward/record.url?scp=85068203036&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-45823-7

DO - 10.1038/s41598-019-45823-7

M3 - Article

C2 - 31263163

AN - SCOPUS:85068203036

SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 9439

ER -

Genome-wide Association Study of Change in Fasting Glucose over time in 13,807 non-diabetic European Ancestry Individuals

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