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Sci Rep. 2019 Jul 1;9(1):9439. 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.

Liu CT1, Merino J2,3,4, Rybin D5, DiCorpo D5, Benke KS6, Bragg-Gresham JL7, Canouil M8, Corre T9,10,11, Grallert H12,13, Isaacs A14,15, Kutalik Z9,11, Lahti J16,17, Marullo L18, Marzi C12,13, Rasmussen-Torvik LJ19, Rocheleau G8,20,21,22,23, Rueedi R10,11, Scapoli C18, Verweij N24, Vogelzangs N25, Willems SM14, Yengo L8, Bakker SJL26, Beilby J27,28,29, Hui J27,28,29,30, Kajantie E31, Müller-Nurasyid M32,33,34,35, Rathmann W36, Balkau B37,38,39, Bergmann S10,11,40, Eriksson JG31,41,42, Florez JC2,3,4,43, Froguel P8,44, Harris T45, Hung J29,46, James AL29,46,47, Kavousi M48, Miljkovic I49, Musk AW29,30,46, Palmer LJ50, Peters A13,51, Roussel R52,53,54, van der Harst P24,55,56, van Duijn CM14, Vollenweider P57, Barroso I58, Prokopenko I59,60,61, Dupuis J5,62, Meigs JB3,43,63, Bouatia-Naji N64,65.

Author information

1
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, MA, 02118, USA. ctliu@bu.edu.
2
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
3
Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
4
Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
5
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, MA, 02118, USA.
6
Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
7
Kidney Epidemiology and Cost Center, Department of Internal Medicine - Nephrology, University of Michigan, Ann Arbor, MI, 48109, USA.
8
CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, 59000, Lille, France.
9
Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
10
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
11
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
12
Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany.
13
German Center for Diabetes Research (DZD), Neuherberg, Germany.
14
Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
15
CARIM School for Cardiovascular Diseases, Maastricht Centre for Systems Biology (MaCSBio) and Department of Biochemistry, Maastricht University, Maastricht, The Netherlands.
16
Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland.
17
Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
18
Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
19
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
20
Preventive and Genomic Cardiology, McGill University Health Centre and Research Institute, Montreal, Quebec, Canada.
21
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
22
The Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
23
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
24
University Medical Center Groningen, Department of Cardiology, University of Groningen, Groningen, The Netherlands.
25
Maastricht University, Department of Epidemiology, Cardiovascular Research Institute Maastricht (CARIM) & Maastricht Centre for Systems Biology (MaCSBio), Maastricht, The Netherlands.
26
University of Groningen, University Medical Center Groningen, Department of Internal Medicine, Groningen, The Netherlands.
27
PathWest Laboratory Medicine of Western Australia, Nedlands WA, 6009, Australia.
28
School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands WA, 6009, Australia.
29
Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Nedlands WA, Australia.
30
School of Population and Global Health, The University of Western Australia, Nedlands WA, 6009, Australia.
31
National Institute for Health and Welfare, Helsinki, Finland.
32
Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
33
Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.
34
Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
35
DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
36
Institute for Biometrics and Epidemiology, German Diabetes Centre, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany.
37
CESP Centre for Research in Epidemiology and Population Health, Villejuif, France.
38
Univ. Paris-Saclay, Univ. Paris Sud, UVSQ, UMRS 1018, F-94807, Villejuif, France.
39
INSERM U1018, CESP, Renal and Cardiovascular Epidemiology, UVSQ-UPS, Villejuif, France.
40
Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.
41
Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
42
Folkhälsan Research Centre, Helsinki, Finland.
43
Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
44
Department of Genomics of Common Disease, Imperial College London, London, United Kingdom.
45
National Institute on Aging, Laboratory of Epidemiology and Population Sciences in Intramural Research Program, Baltimore, MD, USA.
46
School of Medicine and Pharmacology, The University of Western Australia, Nedlands WA, 6009, Australia.
47
Department of Pulmonary Physiology, Sir Charles Gairdner Hospital, Nedlands WA, 6009, Australia.
48
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
49
Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
50
School of Public Health, University of Adelaide, Adelaide, Australia.
51
Institute of Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany.
52
INSERM U1138 (équipe 2: Pathophysiology and Therapeutics of Vascular and Renal Diseases Related to Diabetes, Centre de Recherches des Cordeliers), Paris, France.
53
Univ. Paris 7 Denis Diderot, Sorbonne Paris Cité, France.
54
AP-HP, DHU FIRE, Department of Endocrinology, Diabetology, Nutrition, and Metabolic Diseases, Bichat Claude Bernard Hospital, Paris, France.
55
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
56
Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.
57
Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
58
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
59
Department of Medicine, Imperial College London, London, United Kingdom.
60
Wellcome Centre for Human genetics, University of Oxford, Oxford, United Kingdom.
61
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.
62
The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
63
Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA.
64
INSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris, F-75015, France. nabila.bouatia-naji@inserm.fr.
65
Paris-Descartes University, Sorbonne Paris Cité, Paris, 75006, France. nabila.bouatia-naji@inserm.fr.

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.

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