title: Pathway-Based Genome-Wide Association Studies for Plasma Triglycerides in Obese Females and Normal-Weight Controls.
abstract: Pathway-based analysis as an alternative approach can provide complementary information to single-marker genome-wide association studies (GWASs), which always ignore the epistasis and does not have sufficient power to find rare variants. In this study, using genotypes from a genome-wide association study (GWAS), pathway-based association studies were carried out by a modified Gene Set Enrichment Algorithm (GSEA) method (GenGen) for triglyceride in 1028 unrelated European-American extremely obese females (BMI≥35kg/m2) and normal-weight controls (BMI<25kg/m2), and another pathway association analysis (ICSNPathway) was also used to verify the GenGen result in the same data. The GO0009110 pathway (vitamin anabolism) was among the strongest associations with triglyceride (empirical P<0.001); the result remained significant after FDR correction (P = 0.022). MMAB, an obesity-related locus, included in this pathway. The ABCG1 and BCL6 gene was found in several triglyceride-related pathways (empirical P<0.05), which were also replicated by ICSNPathway (empirical P<0.05, FDR<0.05). We also performed single-marked GWAS using PLINK for TG levels (log-transformed). Significant associations were found between ASTN2 gene SNPs and plasma triglyceride levels (rs7035794, P = 2.24×10-10). Our study suggested that vitamin anabolism pathway, BCL6 gene pathways and ASTN2 gene may contribute to the genetic variation of plasma triglyceride concentrations.
authors: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
authors: Hongxiao
authors: H
authors: Jiao
authors: Zilkha Neurogenetic Institute and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, United States of America.
authors: Kai
authors: K
authors: Wang
authors: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
authors: Fuhua
authors: F
authors: Yang
authors: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, United States of America; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, United States of America.
authors: Struan F A
authors: SF
authors: Grant
authors: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, United States of America; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, United States of America.
authors: Hakon
authors: H
authors: Hakonarson
authors: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, United States of America.
authors: R Arlen
authors: RA
authors: Price
authors: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China; Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, United States of America.
authors: Wei-Dong
authors: WD
authors: Li
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D009765:Obesity / Q000097:blood* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood*
chemical_list: D005819:Genetic Markers; D014280:Triglycerides