Studies of metabolic phenotypic correlates of 15 obesity associated gene variants

• Published in: PloS one Vol. 6; no. 9; p. e23531
• Main Authors: Sandholt, Camilla Helene, Vestmar, Marie Aare, Bille, Dorthe Sadowa, Borglykke, Anders, Almind, Katrine, Hansen, Lars, Sandbæk, Annelli, Lauritzen, Torsten, Witte, Daniel, Jørgensen, Torben, Pedersen, Oluf, Hansen, Torben
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.09.2011; Public Library of Science (PLoS)
• Subjects: Adipose tissue; Alleles; Analysis; Anthropometry; Biology; Body mass; Body mass index; Body weight; Brain-derived neurotrophic factor; Correlation analysis; Diabetes mellitus; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Disease susceptibility; Gene Frequency; Genes; Genetic aspects; Genetic Loci - genetics; Genetic research; Genome-wide association studies; Genome-Wide Association Study; Genomes; Health risks; Humans; Loci; Medicine; Middle Aged; Npc1 protein; Obesity; Obesity - genetics; Obesity - metabolism; Obesity, Morbid - genetics; Obesity, Morbid - metabolism; Overweight; Phenotype; Polymorphism, Single Nucleotide; Risk Factors; Rodents; Type 2 diabetes; Denmark; Aarhus Denmark
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0023531

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. 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. 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 = 7.8×10(-4))). 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.