Kernel machine SNP set analysis finds the association of BUD13, ZPR1, and APOA5 variants with metabolic syndrome in Tehran Cardio-metabolic Genetics Study.

Journal: Scientific reports
PMID:

Abstract

Metabolic syndrome (MetS) is one of the most important risk factors for cardiovascular disease. The 11p23.3 chromosomal region plays a potential role in the pathogenesis of MetS. The present study aimed to assess the association between 18 single nucleotide polymorphisms (SNPs) located at the BUD13, ZPR1, and APOA5 genes with MetS in the Tehran Cardio-metabolic Genetics Study (TCGS). In 5421 MetS affected and non-affected participants, we analyzed the data using two models. The first model (MetS model) examined SNPs' association with MetS. The second model (HTg-MetS Model) examined the association of SNPs with MetS affection participants who had a high plasma triglyceride (TG). The four-gamete rules were used to make SNP sets from correlated nearby SNPs. The kernel machine regression models and single SNP regression evaluated the association between SNP sets and MetS. The kernel machine results showed two sets over three sets of correlated SNPs have a significant joint effect on both models (p < 0.0001). Also, single SNP regression results showed that the odds ratios (ORs) for both models are almost similar; however, the p-values had slightly higher significance levels in the HTg-MetS model. The strongest ORs in the HTg-MetS model belonged to the G allele in rs2266788 (MetS: OR = 1.3, p = 3.6 × 10; HTg-MetS: OR = 1.4, p = 2.3 × 10) and the T allele in rs651821 (MetS: OR = 1.3, p = 2.8 × 10; HTg-MetS: OR = 1.4, p = 3.6 × 10). In the present study, the kernel machine regression models could help assess the association between the BUD13, ZPR1, and APOA5 gene variants (11p23.3 region) with lipid-related traits in MetS and MetS affected with high TG.

Authors

  • Sajedeh Masjoudi
    Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box 19195-4763, Tehran, Iran.
  • Bahareh Sedaghati-Khayat
    Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box 19195-4763, Tehran, Iran.
  • Niloufar Javanrouh Givi
    Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box 19195-4763, Tehran, Iran.
  • Leila Najd Hassan Bonab
    Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box 19195-4763, Tehran, Iran.
  • Fereidoun Azizi
    Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran (FA)
  • Maryam S Daneshpour
    Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box 19195-4763, Tehran, Iran. daneshpour@sbmu.ac.ir.