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 = 7.861024)).
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.