title: Genetic association analysis of polymorphisms in PSD3 gene with obesity, type 2 diabetes, and HDL cholesterol.
abstract: BACKGROUND
  The pleckstrin and Sec7 domain-containing 3 (PSD3) gene has been linked to immune diseases. We examined whether the genetic variants within the PSD3 gene are associated with obesity, type 2 diabetes (T2D), and high-density lipoprotein (HDL) cholesterol level.
  
  
  METHODS
  Multiple logistic regression model and linear regression model were used to examine the associations of 259 single nucleotide polymorphisms (SNPs) within the PSD3 gene with obesity and T2D as binary traits, and HDL level as a continuous trait using the Marshfield data, respectively. A replication study of obesity was conducted using the Health Aging and Body Composition (Health ABC) sample.
  
  
  RESULTS
  23SNPs were associated with obesity (p<0.05) in the Marshfield sample and rs4921966 revealed the strongest association (p=3.97×10-6). Of the 23SNPs, 20 were significantly associated with obesity in the meta-analysis of two samples (p<0.05). Furthermore, 6SNPs revealed associations with T2D in the Marshfield data (top SNP rs12156368 with p=3.05×10-3); while two SNPs (rs6983992 and rs7843239) were associated with both obesity and T2D (p=0.0188 and 0.023 for obesity and p=8.47×10-3and 0.0128 for T2D, respectively). Furthermore, 11SNPs revealed associations with HDL level (top SNP rs13254772 with p=2.79×10-3) in the Marshfield data; meanwhile rs7009615 was associated with both T2D (p=0.038) and HDL level (p=4.44×10-3). In addition, haplotype analyses further supported the results of single SNP analysis.
  
  
  CONCLUSIONS
  Common variants in PSD3 were associated with obesity, T2D and HDL level. These findings add important new insights into the pathogenesis of obesity, T2D and HDL cholesterol.
authors.affiliation: Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Gong
authors.affiliation: Department of Health and Biomedical Science, University of Texas Rio Grande Valley, Brownsville, TX, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Owusu
authors.affiliation: Department of Family Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Bailey
authors.affiliation: Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN, USA. Electronic address: wangk@etsu.edu.
authors.forename: Kesheng
authors.initials: K
authors.lastname: Wang
mesh_terms: D000368:Aged; D008076:Cholesterol, HDL / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D014644:Genetic Variation; D020662:Guanine Nucleotide Exchange Factors; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D008076:Cholesterol, HDL; D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; C109970:PSD protein, human
keywords: HDL cholesterol; Haplotype; Meta-analysis; Obesity; PSD3; Type 2 diabetes