Polymorphisms of PSD3 gene associated with obesity in two Caucasian samples

Obesity has become a global epidemic and contributes to the increasing burden of diabetes, cardiovascular disease, osteoarthritis, and a range of cancers. The pleckstrin and Sec7 domain containing 3 gene (PSD3) is a potential tumor suppressor gene for some cancers and is associated with immune diseases. We hypothesized that PSD3 gene polymorphisms may play a role in obesity. We examined associations of 163 single-nucleotide polymorphisms (SNPs) within the PSD3 gene with obesity using one Caucasian sample from the Marshfield sample (1,442 obese and 2,122 controls), and conducted the replication using the Study of Addiction: Genetics and Environment (SAGE) sample (254 obese and 776 controls). Logistic regression models in PLINK software were used to examine the associations of genetic variants with obesity as a binary trait, adjusted for age and sex. Single marker analysis showed that 20 SNPs in the Marshfield sample were associated with obesity (P<0.05). SNP rs4921966 revealed the strongest association with obesity (P = 3.97 x 10^-6); while the next best signal was rs11995692 (P = 1.97 x 10^-5). The third best associated SNP was rs7007413 (P = 2.65 x 10^-5). SNPs rs11995692 and rs7007413 were also found to be associated with obesity in the SAGE sample (P = 0.0398 and 0.0496, respectively). In addition, 5 SNPs were associated with obesity with P<0.01 in the SAGE sample (rs11204003, rs11783114, rs1896201, rs11987871 and rs1025229 with P= 5.96 x10^-5, 0.00525, 0.00699, 0.00819 and 0.0092, respectively). These findings offer the potential for new insights into the pathogenesis of obesity.