Journal
PLOS ONE
Volume 6, Issue 9, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0023531
Keywords
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Categories
Funding
- Novo Nordisk Foundation
- Lundbeck Foundation Centre
- Danish Health Research Council
- FOOD Study Group/the Danish Ministry of Food, Agriculture and Fisheries and Ministry of Family and Consumer Affairs [2101-05-0044]
- Novo Nordisk A/S Research & Development Corporate Research Affairs
- Danish Ministry of Science Technology and Innovation
- Faculty of Health Sciences of Aarhus University
- Danish Clinical Intervention Research Academy
- Danish Diabetes Association
- European Commission [LSHM-CT-2005-018734]
- The Danish Obesity Research centre (DanORC)
- Danish Council for Strategic Research [2101-06-0005]
- Danish Research Counsil
- Danish Centre for Health Technology Assessment
- Novo Nordisk Inc.
- Research Foundation of Copenhagen County
- Ministry of Internal Affaires and Health
- Danish Heart Foundation
- Danish Pharmaceutical Association
- Augustinus Foundation
- Ib Henriksen Foundation
- Becket Foundation
- National Health Services in the counties of Copenhagen, Aarhus, Ringkobing, Ribe
- South Jutland in Denmark
- Danish Research Foundation for General Practice
- Danish Centre for Evaluation and Health Technology Assessment
- National Board of Health
- Danish Medical Research Council
- Aarhus University Research Foundation
- Novo Nordisk A/S
- Novo Nordisk Scandinavia AB, ASTRA Denmark
- Pfizer Denmark
- GlaxoSmithKline Pharma Denmark
- SERVIER Denmark A/S
- HemoCue Denmark A/S
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Aims: Genome-wide association studies have identified novel BMI/obesity associated susceptibility loci. The purpose of this study is to determine associations with overweight, obesity, morbid obesity and/or general adiposity in a Danish population. Moreover, we want to investigate if these loci associate with type 2 diabetes and to elucidate potential underlying metabolic mechanisms. Methods: 15 gene variants in 14 loci including TMEM18 (rs7561317), SH2B1 (rs7498665), KCTD15 (rs29941), NEGR1 (rs2568958), ETV5 (rs7647305), BDNF (rs4923461, rs925946), SEC16B (rs10913469), FAIM2 (rs7138803), GNPDA2 (rs10938397), MTCH2 (rs10838738), BAT2 (rs2260000), NPC1 (rs1805081), MAF (rs1424233), and PTER (rs10508503) were genotyped in 18,014 middle-aged Danes. Results: Five of the 15 gene variants associated with overweight, obesity and/or morbid obesity. Per allele ORs ranged from 1.15-1.20 for overweight, 1.10-1.25 for obesity, and 1.41-1.46 for morbid obesity. Five of the 15 variants moreover associated with increased measures of adiposity. BDNF rs4923461 displayed a borderline BMI-dependent protective effect on type 2 diabetes (0.87 (0.78-0.96, p = 0.008)), whereas SH2B1 rs7498665 associated with nominally BMI-independent increased risk of type 2 diabetes (1.16 (1.07-1.27, p = 7.8x10(-4))). Conclusions: Associations with overweight and/or obesity and measures of obesity were confirmed for seven out of the 15 gene variants. The obesity risk allele of BDNF rs4923461 protected against type 2 diabetes, which could suggest neuronal and peripheral distinctive ways of actions for the protein. SH2B1 rs7498665 associated with type 2 diabetes independently of BMI.
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