TY - JOUR
T1 - Genetic association analysis of polymorphisms in PSD3 gene with obesity, type 2 diabetes, and HDL cholesterol
AU - Gong, Shaoqing
AU - Xu, Chun
AU - Wang, Liang
AU - Liu, Ying
AU - Owusu, Daniel
AU - Bailey, Beth A.
AU - Li, Yujing
AU - Wang, Kesheng
N1 - Funding Information:
Funding support for the Personalized Medicine Research Project (PMRP) was provided through a cooperative agreement (U01HG004608) with the National Human Genome Research Institute (NHGRI), with additional funding from the National Institute for General Medical Sciences (NIGMS). The samples used for PMRP analyses were obtained with funding from Marshfield Clinic, Health Resources Service Administration Office of Rural Health Policy grant number D1A RH00025, and Wisconsin Department of Commerce Technology Development Fund contract number TDF FYO10718. Funding support for genotyping, which was performed at Johns Hopkins University, was provided by the NIH (U01HG004438). Assistance with phenotype harmonization and genotype cleaning was provided by the eMERGE Administrative Coordinating Center (U01HG004603) and the National Center for Biotechnology Information (NCBI). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000170.v1.p1. Funding support for the “CIDR Visceral Adiposity Study” was provided through the Division of Aging Biology and the Division of Geriatrics and Clinical Gerontology, NIA. The CIDR Visceral Adiposity Study includes a genome-wide association study funded as part of the Division of Aging Biology and the Division of Geriatrics and Clinical Gerontology, NIA. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by Heath ABC Study Investigators. The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000169.v1.p1. This study was approved by the Internal Review Board (IRB), East Tennessee State University.
Publisher Copyright:
© 2017
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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 23 SNPs were associated with obesity (p < 0.05) in the Marshfield sample and rs4921966 revealed the strongest association (p = 3.97 × 10−6). Of the 23 SNPs, 20 were significantly associated with obesity in the meta-analysis of two samples (p < 0.05). Furthermore, 6 SNPs 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 × 10−3 and 0.0128 for T2D, respectively). Furthermore, 11 SNPs 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.
AB - 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 23 SNPs were associated with obesity (p < 0.05) in the Marshfield sample and rs4921966 revealed the strongest association (p = 3.97 × 10−6). Of the 23 SNPs, 20 were significantly associated with obesity in the meta-analysis of two samples (p < 0.05). Furthermore, 6 SNPs 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 × 10−3 and 0.0128 for T2D, respectively). Furthermore, 11 SNPs 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.
KW - HDL cholesterol
KW - Haplotype
KW - Meta-analysis
KW - Obesity
KW - PSD3
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85013665405&partnerID=8YFLogxK
U2 - 10.1016/j.diabres.2017.02.006
DO - 10.1016/j.diabres.2017.02.006
M3 - Article
C2 - 28237857
AN - SCOPUS:85013665405
VL - 126
SP - 105
EP - 114
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
SN - 0168-8227
ER -