New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
Copyright policy )New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
- University of North Carolina at Chapel Hill United States
- Leibniz Association Germany
- TU Dresden Germany
- Uppsala University Sweden
- Karolinska Institute Sweden
Netherlands Twin Register (NTR), Blood Glucose, [SDV]Life Sciences [q-bio], CIRCADIAN CLOCK, TRIGLYCERIDE LEVELS, Delta-5 Fatty Acid Desaturase, Databases, Genetic, Homeostasis, T2D, glucose, GENETICS & HEREDITY, Anders Hamsten on behalf of Procardis Consortium, Child, EMC MGC-02-96-01, genome wide association study, Genetics & Heredity, PLASMA-GLUCOSE, COMMON VARIANTS, Single Nucleotide, 11 Medical And Health Sciences, Fasting, MAGIC investigators, [SDV] Life Sciences [q-bio], MODEL ASSESSMENT, /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, Life Sciences & Biomedicine, Type 2, EMC COEUR-09, Adult, 571, /dk/atira/pure/subjectarea/asjc/1300/1311, ESSENTIAL COMPONENTS, Adolescent, DNA Copy Number Variations, name=Genetics, Adolescent; Adult; Alleles; Blood Glucose/genetics; Blood Glucose/metabolism; Child; DNA Copy Number Variations/genetics; Databases, Genetic; Diabetes Mellitus, Type 2/genetics; Fasting/blood; Gene Expression Regulation; Genetic Loci/genetics; Genetic Predisposition to Disease; Genome-Wide Association Study; Homeostasis/genetics; Humans; Meta-Analysis as Topic; Polymorphism, Single Nucleotide/genetics; Quantitative Trait Loci/genetics; Quantitative Trait, Heritable; Reproducibility of Results, Quantitative Trait Loci, 610, DIAGRAM Consortium, INSULIN-SECRETION, Polymorphism, Single Nucleotide, Article, Databases, Quantitative Trait, Quantitative Trait, Heritable, Genetic, SDG 3 - Good Health and Well-being, Meta-Analysis as Topic, genome wide association study; glucose; diabetes type 2, Diabetes Mellitus, Genetics, GIANT Consortium, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, Heritable, Global BPgen Consortium, Alleles, Science & Technology, diabetes type 2, genome-wide association beta-cell dysfunction plasma-glucose insulin-secretion triglyceride levels essential components model assessment common variants circadian clock disease risk, DISEASE RISK, Reproducibility of Results, 06 Biological Sciences, MAGIC, name=SDG 3 - Good Health and Well-being, EMC MM-01-39-02, Diabetes Mellitus, Type 2, Gene Expression Regulation, Genetic Loci, BETA-CELL DYSFUNCTION, Developmental Biology, Genome-Wide Association Study
Netherlands Twin Register (NTR), Blood Glucose, [SDV]Life Sciences [q-bio], CIRCADIAN CLOCK, TRIGLYCERIDE LEVELS, Delta-5 Fatty Acid Desaturase, Databases, Genetic, Homeostasis, T2D, glucose, GENETICS & HEREDITY, Anders Hamsten on behalf of Procardis Consortium, Child, EMC MGC-02-96-01, genome wide association study, Genetics & Heredity, PLASMA-GLUCOSE, COMMON VARIANTS, Single Nucleotide, 11 Medical And Health Sciences, Fasting, MAGIC investigators, [SDV] Life Sciences [q-bio], MODEL ASSESSMENT, /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, Life Sciences & Biomedicine, Type 2, EMC COEUR-09, Adult, 571, /dk/atira/pure/subjectarea/asjc/1300/1311, ESSENTIAL COMPONENTS, Adolescent, DNA Copy Number Variations, name=Genetics, Adolescent; Adult; Alleles; Blood Glucose/genetics; Blood Glucose/metabolism; Child; DNA Copy Number Variations/genetics; Databases, Genetic; Diabetes Mellitus, Type 2/genetics; Fasting/blood; Gene Expression Regulation; Genetic Loci/genetics; Genetic Predisposition to Disease; Genome-Wide Association Study; Homeostasis/genetics; Humans; Meta-Analysis as Topic; Polymorphism, Single Nucleotide/genetics; Quantitative Trait Loci/genetics; Quantitative Trait, Heritable; Reproducibility of Results, Quantitative Trait Loci, 610, DIAGRAM Consortium, INSULIN-SECRETION, Polymorphism, Single Nucleotide, Article, Databases, Quantitative Trait, Quantitative Trait, Heritable, Genetic, SDG 3 - Good Health and Well-being, Meta-Analysis as Topic, genome wide association study; glucose; diabetes type 2, Diabetes Mellitus, Genetics, GIANT Consortium, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, Heritable, Global BPgen Consortium, Alleles, Science & Technology, diabetes type 2, genome-wide association beta-cell dysfunction plasma-glucose insulin-secretion triglyceride levels essential components model assessment common variants circadian clock disease risk, DISEASE RISK, Reproducibility of Results, 06 Biological Sciences, MAGIC, name=SDG 3 - Good Health and Well-being, EMC MM-01-39-02, Diabetes Mellitus, Type 2, Gene Expression Regulation, Genetic Loci, BETA-CELL DYSFUNCTION, Developmental Biology, Genome-Wide Association Study
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