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Evidence for age as a modifier of genetic associations for lipid levels

Logan Dumitrescu1, Kristin Brown-Gentry, Robert Goodloe

  • 1Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232, USA.

Annals of Human Genetics
|July 23, 2011
PubMed

Insights

This study used genome-wide association studies in children to find new genetic variants affecting lipid levels. A key finding was an age-dependent link between the SGSM2 gene variant rs2429917 and LDL cholesterol.

Area of Science:

  • Genetics
  • Biochemistry
  • Pediatrics

Background:

  • Plasma lipid concentrations are crucial cardiovascular disease risk factors.
  • Genetic variants play a role in lipid metabolism, but many remain undiscovered.
  • Pediatric populations offer unique opportunities for identifying novel genetic associations.

Purpose of the Study:

  • To identify novel genetic variants influencing plasma lipid concentrations using a genome-wide association study (GWAS) in children.
  • To validate initial findings in independent pediatric and adult cohorts.
  • To investigate age-dependent genetic effects on lipid levels.

Main Methods:

  • Conducted a GWAS in 411 children from St. Jude Children's Research Hospital.
  • Replicated promising associations (p < 10(-5)) in 1040 youths and 3508 adults from NHANES III.
  • Tested for gene-age interactions in the NHANES III cohort.

Main Results:

  • Three genotype-phenotype associations replicated in NHANES III youths, and three in NHANES III adults; no single association was significant in both.
  • The most significant association in African descent youths was between LDL-C and intronic rs2429917 (p=0.009).
  • A significant age-dependent association (p=0.024) was found between SGSM2 rs2429917 and LDL-C in NHANES III participants.

Conclusions:

  • Children are valuable for discovering novel genetic variants related to complex traits like lipid levels.
  • Age-dependent genetic effects are important to consider in lipid association studies.
  • The SGSM2 rs2429917 variant shows an age-dependent association with LDL-C, highlighting its potential role in lipid regulation.

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