Familial aggregation and linkage analysis with covariates for metabolic syndrome risk factors

Gene. 2018 Jun 15:659:118-122. doi: 10.1016/j.gene.2018.03.033. Epub 2018 Mar 14.

Abstract

Background: Mechanisms of metabolic syndrome (MetS) causation are complex, genetic and environmental factors are important factors for the pathogenesis of MetS In this study, we aimed to evaluate familial and genetic influences on metabolic syndrome risk factor and also assess association between FTO (rs1558902 and rs7202116) and CETP(rs1864163) genes' single nucleotide polymorphisms (SNP) with low HDL_C in the Tehran Lipid and Glucose Study (TLGS).

Materials and methods: The design was a cross-sectional study of 1776 members of 227 randomly-ascertained families. Selected families contained at least one affected metabolic syndrome and at least two members of the family had suffered a loss of HDL_C according to ATP III criteria. In this study, after confirming the familial aggregation with intra-trait correlation coefficients (ICC) of Metabolic syndrome (MetS) and the quantitative lipid traits, the genetic linkage analysis of HDL_C was performed using conditional logistic method with adjusted sex and age.

Results: The results of the aggregation analysis revealed a higher correlation between siblings than between parent-offspring pairs representing the role of genetic factors in MetS. In addition, the conditional logistic model with covariates showed that the linkage results between HDL_C and three marker, rs1558902, rs7202116 and rs1864163 were significant.

Conclusions: In summary, a high risk of MetS was found in siblings confirming the genetic influences of metabolic syndrome risk factor. Moreover, the power to detect linkage increases in the one parameter conditional logistic model regarding the use of age and sex as covariates.

Keywords: Aggregation analysis; Conditional logistic model; HDL_C; Linkage analysis; Mets.

MeSH terms

  • Adult
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics*
  • Cholesterol Ester Transfer Proteins / genetics*
  • Cholesterol, HDL / blood*
  • Cholesterol, HDL / genetics
  • Cross-Sectional Studies
  • Female
  • Genetic Linkage
  • Humans
  • Iran
  • Logistic Models
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci
  • Young Adult

Substances

  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human