1 Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet2 Section for Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet3 Department of Public Health, Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet4 unknown5 Odontologisk Institut, Tandlægeskolen6 Section for Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet
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).
Twin Research and Human Genetics, 2012, Vol 15, Issue 6, p. 691-9
Clinical Trial; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Twin Study; 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