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ResearchIn-Press PreviewMetabolismNephrology
Open Access | 10.1172/JCI160959
1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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Okabe, J.
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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Thomas, M.
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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Huang, Y.
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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Ma, R.
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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Chan, J.
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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Rossing, P.
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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1Department of Diabetes, Monash University, Melbourne, Australia
2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
3School of Life and Environmental Sciences, Monash University, Melbourne, Australia
4Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
5Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
6School of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong
7Diabetes, Theptarin Hospital, Bangkok, Thailand
8Department of Anatomy, American University of Beirut, Beirut, Lebanon
9American University of Beirut, Beirut, Lebanon
10Complications Research, Steno Diabetes Center, Copenhagen, Denmark
11The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong
12Epigenetics in Human Health and Disease Laboratory, Monash University, Melbourne, Australia
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El-Osta, A.
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Published January 12, 2023 - More info
Diabetic nephropathy (DN) is a polygenic disorder with few risk variants showing robust replication in large-scale genome-wide association studies. To understand the role of DNA methylation, it is important to have the prevailing genomic view to distinguish key sequence elements that influence gene expression. This is particularly challenging for DN because genome wide methylation patterns are poorly defined. While methylation is known to alter gene expression the importance of this causal relationship is obscured by array-based technologies since coverage outside promoter regions is low. To overcome these challenges, we performed methylation sequencing using leukocytes derived from participants of the Finnish Diabetic Nephropathy (FinnDiane) type 1 diabetes (T1D) study (n=39) that was subsequently replicated in a larger validation cohort (n=296). Gene body related regions made up >60% of the methylation differences and emphasised the importance of methylation sequencing. We observe differentially methylated genes associated with DN (DDN) in three independent T1D registries originating from Denmark (n=445), Hong Kong (n=107) and Thailand (n=130). Reduced DNA methylation at CTCF and Pol2B sites were tightly connected with DN pathways that include insulin signalling, lipid metabolism and fibrosis. To define the pathophysiological significance of these population findings, methylation indices were assessed in human renal cells such as podocytes and proximal convoluted tubules. The expression of core genes was associated with reduced methylation, elevated CTCF and Pol2B binding and the activation of insulin signalling phosphoproteins in hyperglycaemic cells. These experimental observations also closely parallel methylation-mediated regulation in human macrophage and vascular endothelial cells.