A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol

Twin Res Hum Genet. 2012 Dec;15(6):691-9. doi: 10.1017/thg.2012.63. Epub 2012 Oct 3.

Abstract

Genome-wide association analysis on monozygotic twin-pairs offers a route to discovery of gene environment interactions through testing for variability loci associated with sensitivity to individual environment/lifestyle. We present a genome-wide scan of loci associated with intra-pair differences in serum lipid and apolipoprotein levels. We report data for 1,720 monozygotic female twin-pairs from GenomEUtwin project with 2.5 million SNPs, imputed or genotyped, and measured serum lipid fractions for both twins. We found one locus associated with intra-pair differences in high-density lipoprotein cholesterol, rs2483058 in an intron of SRGAP2, where twins carrying the C allele are more sensitive to environmental factors(P=3.98 x 10-8). We followed up the association in further genotyped monozygotic twins (N= 1,261),which showed a moderate association for the variant (P= 0.200, same direction of an effect). In addition,we report a new association on the level of apolipoprotein A-ll (P= 4.03 x 1 o-8).

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Apolipoprotein A-II / blood
  • Apolipoprotein A-II / genetics
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / genetics*
  • Female
  • GTPase-Activating Proteins / genetics*
  • GTPase-Activating Proteins / metabolism
  • Gene-Environment Interaction*
  • Genetic Loci*
  • Genome-Wide Association Study*
  • Humans
  • Introns
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Twins, Monozygotic / genetics*

Substances

  • Apolipoprotein A-II
  • Cholesterol, HDL
  • GTPase-Activating Proteins
  • SRGAP2 protein, human