A Genome-Wide Association Study of Monozygotic Twin-Pairs Suggests a Locus Related to Variability of Serum High-Density Lipoprotein Cholesterol

Ida Surakka, John B Whitfield, Markus Perola, Peter M Visscher, Grant W Montgomery, Mario Falchi, Gonneke Willemsen, Eco J C de Geus, Patrik K E Magnusson, Kaare Christensen, Thorkild I A Sørensen, Kirsi H Pietiläinen, Taina Rantanen, Kaisa Silander, Elisabeth Widén, Juha Muilu, Iffat Rahman, Ulrika Liljedahl, Ann-Christine Syvänen, Aarno PalotieJaakko Kaprio, Kirsten O Kyvik, Nancy L Pedersen, Dorret I Boomsma, Tim Spector, Nicholas G Martin, Samuli Ripatti*, Leena Peltonen, GenomEUtwin Project

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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 = 3.98x10(-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-II (P = 4.03x10(-8)).

Original languageEnglish
Pages (from-to)691-699
Number of pages9
JournalTWIN RESEARCH AND HUMAN GENETICS
Volume15
Issue number6
DOIs
Publication statusPublished - Dec 2012

Keywords

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

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