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Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals
- Source :
- PLoS Genetics; Vol 8, Dastani, Z, Hivert, M F, Timpson, N J, Perry, J R, Yuan, X, Scott, R A, Henneman, P, Heid, I M, Kizer, J R, Lyytikäinen, L P, Fuchsberger, C, Tanaka, T, Morris, A P, Small, K, Isaacs, A, Beekman, M, Coassin, S, Lohman, K, Qi, L, Kanoni, S, Pankow, J S, Uh, H W, Wu, Y, Bidulescu, A, Rasmussen-Torvik, L J, Greenwood, C M, Ladouceur, M, Grimsby, J, Manning, A K, Liu, C T, Kooner, J, Mooser, V E, Vollenweider, P, Kapur, K A, Chambers, J, Wareham, N J, Langenberg, C, Frants, R, Willems van Dijk, K, Oostra, B A, Willems, S M, Lamina, C, Winkler, T W, Psaty, B M, Tracy, R P, Brody, J, Chen, I, Viikari, J, Kähönen, M, Pramstaller, P P, Evans, D M, St Pourcain, B, Sattar, N, Wood, A R, Bandinelli, S, Carlson, O D, Egan, J M, Böhringer, S, van Heemst, D, Kedenko, L, Kristiansson, K, Nuotio, M L, Loo, B M, Harris, T, Garcia, M, Kanaya, A, Haun, M, Klopp, N, Wichmann, H E, Deloukas, P, Katsareli, E, Couper, D J, Duncan, B B, Kloppenburg, M, Adair, L S, Borja, J B, Hottenga, J J, de Geus, E J C, Willemsen, G, Boomsma, D I, Wilson, J G, Musani, G, Guo, X, Johnson, T, Semple, R, Teslovich, T M, Allison, M A, Redline, S, Buxbaum, S G, Mohlke, K L, Meulenbelt, I, Ballantyne, C M, Dedoussis, G V, Hu, F B, Liu, Y, Paulweber, B, Spector, T D, Slagboom, P E, Ferrucci, L, Jula, A, Perola, M, Raitakari, O, Florez, J C, Salomaa, V, Eriksson, J G, Frayling, T M, Hicks, A A, Lehtimäki, T, Smith, G D, Siscovick, D S, Kronenberg, F, van Duijn, C M, Loos, R J, Waterworth, D, Meigs, J B, Dupuis, J, Richards, J B, Posthuma, D, Penninx, B W J H, Vogelzangs, N & Kathiresan, S 2012, ' Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals ', PLoS Genetics, vol. 8, no. 3, e1002607, pp. e1002607 . https://doi.org/10.1371/journal.pgen.1002607, Plos Genetics, 8(3). Public Library of Science, PLoS Genet. 8:e1002607 (2012), DIAGRAM+ Consortium, MAGIC Consortium & GLGC Consortium 2012, ' Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits : a multi-ethnic meta-analysis of 45,891 individuals ', P L o S Genetics, vol. 8, no. 3, pp. e1002607 . https://doi.org/10.1371/journal.pgen.1002607, PLoS Genetics (print), 8(3). Public Library of Science, Dastani, Z, Hivert, M-F, Timpson, N, Perry, J R B, Yuan, X, Scott, R A, Henneman, P, Heid, I M, Kizer, J R, Lyytikäinen, L-P, Fuchsberger, C, Tanaka, T, Morris, A P, Small, K, Isaacs, A, Beekman, M, Coassin, S, Lohman, K, Qi, L, Kanoni, S, Pankow, J S, Uh, H-W, Wu, Y, Bidulescu, A, Rasmussen-Torvik, L J, Greenwood, C M T, Ladouceur, M, Grimsby, J, Manning, A K, Liu, C-T, Kooner, J, Mooser, V E, Vollenweider, P, Kapur, K A, Chambers, J, Wareham, N J, Langenberg, C, Wilson, J G, Navarro, P, Morris, A, Rudan, I, Campbell, H, Wilson, J F, Hayward, C, Sharp, S J, Vitart, V, Wild, S H, Wright, A F & Thompson, J R & Hastie, N D 2012, ' Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits : a multi-ethnic meta-analysis of 45,891 individuals ', PLoS Genetics, vol. 8, no. 3, pp. e1002607 . https://doi.org/10.1371/journal.pgen.1002607, PLoS Genetics, 8(3), PLoS Genetics, Vol 8, Iss 3, p e1002607 (2012), PLoS Genetics, PLoS Genetics, 8(3):e1002607. Public Library of Science, PLoS genetics, 8(3). Public Library of Science, Dastani, Z, Hivert, M-F, Timpson, N, Perry, J R B, Yuan, X, Scott, R A, Henneman, P, Heid, I M, Kizer, J R, Lyytikäinen, L-P, Fuchsberger, C, Tanaka, T, Morris, A P, Small, K, Isaacs, A, Beekman, M, Coassin, S, Lohman, K, Qi, L, Kanoni, S, Pankow, J S, Uh, H-W, Wu, Y, Bidulescu, A, Rasmussen-Torvik, L J, Greenwood, C M T, Ladouceur, M, Grimsby, J, Manning, A K, Liu, C-T, Kooner, J, Mooser, V E, Vollenweider, P, Kapur, K A, Chambers, J, Wareham, N J, Langenberg, C, Frants, R, Willems-Vandijk, K, Oostra, B A, Willems, S M, Lamina, C, Winkler, T W, Psaty, B M, Tracy, R P, Brody, J, Chen, I, Borch-Johnsen, K, Kyvik, K O & DIAGRAM Consortium 2012, ' Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits : a multi-ethnic meta-analysis of 45,891 individuals ', P L o S Genetics, vol. 8, no. 3, pp. e1002607 . https://doi.org/10.1371/journal.pgen.1002607, Plos Genetics, vol. 8, no. 3, pp. e1002607
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8–1.2×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<br />Author Summary Serum adiponectin levels are highly heritable and are inversely correlated with the risk of type 2 diabetes (T2D), coronary artery disease, stroke, and several metabolic traits. To identify common genetic variants associated with adiponectin levels and risk of T2D and metabolic traits, we conducted a meta-analysis of genome-wide association studies of 45,891 multi-ethnic individuals. In addition to confirming that variants at the ADIPOQ and CDH13 loci influence adiponectin levels, our analyses revealed that 10 new loci also affecting circulating adiponectin levels. We demonstrated that expression levels of several genes in these candidate regions are associated with serum adiponectin levels. Using a powerful novel method to assess the contribution of the identified variants with other traits using summary-level results from large-scale GWAS consortia, we provide evidence that the risk alleles for adiponectin are associated with deleterious changes in T2D risk and metabolic syndrome traits (triglycerides, HDL, post-prandial glucose, insulin, and waist-to-hip ratio), demonstrating that the identified loci, taken together, impact upon metabolic disease.
- Subjects :
- Netherlands Twin Register (NTR)
Male
Insulin Resistance/genetics
VARIANTS
0302 clinical medicine
POPULATION
African Americans
blood/genetics
0303 health sciences
education.field_of_study
Adiponectin/blood
Adiponectin/genetics
Asian Continental Ancestry Group
Cholesterol, HDL/genetics
Diabetes Mellitus, Type 2/genetics
European Continental Ancestry Group
Female
Gene Expression
Genetic Predisposition to Disease
Genome-Wide Association Study
Glucose Tolerance Test
Humans
Metabolic Networks and Pathways
Polymorphism, Single Nucleotide
Waist-Hip Ratio
Global B Pgen Consortium
MAGIC investigators
3. Good health
Cholesterol
Medicine
Adiponectin
Type 2
medicine.medical_specialty
HDL
Biolääketieteet - Biomedicine
Single-nucleotide polymorphism
DIAGRAM Consortium
White People
Molecular Genetics
GLGC Consortium
03 medical and health sciences
Asian People
SDG 3 - Good Health and Well-being
GIANT Consortium
Diabetes Mellitus
Genetics
DIAGRAM+ Consortium
GENOME-WIDE ASSOCIATION
Polymorphism
education
Biology
Molecular Biology
Ecology, Evolution, Behavior and Systematics
0604 Genetics
Science & Technology
GLGC Investigators
nutritional and metabolic diseases
ta3121
medicine.disease
Obesity
Black or African American
blood/genetics, African Americans, Asian Continental Ancestry Group, Cholesterol
genetics, Diabetes Mellitus
genetics, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Insulin Resistance
genetics, Male, Metabolic Networks and Pathways, Polymorphism
Single Nucleotide, Waist-Hip Ratio
Endocrinology
Diabetes Mellitus, Type 2
Developmental Biology
Type 2/genetics
Cancer Research
Type 2 diabetes
QH426-470
030204 cardiovascular system & hematology
LIPID CONCENTRATIONS
GENETICS & HEREDITY
Genetics (clinical)
RISK
2. Zero hunger
INSULIN-RESISTANCE
Glucose tolerance test
medicine.diagnostic_test
MAGIC Consortium
Single Nucleotide
ADIPOSE-TISSUE
CORONARY-ARTERY-DISEASE
Life Sciences & Biomedicine
Research Article
Clinical Research Design
GENETIC-BASIS
Population
Insulin resistance
Internal medicine
Diabetes mellitus
medicine
ddc:610
030304 developmental biology
RECEPTOR
Cholesterol, HDL
Human Genetics
HDL/genetics
3121 General medicine, internal medicine and other clinical medicine
MuTHER Consortium
3111 Biomedicine
Procardis Consortium
Insulin Resistance
Subjects
Details
- ISSN :
- 15537404 and 15537390
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- PLoS Genetics
- Accession number :
- edsair.doi.dedup.....90a4406ebf3ddb6c441a5238120a0cac
- Full Text :
- https://doi.org/10.1371/journal.pgen.1002607