Suchergebnisse

AbstractIn twin studies of cardiovascular disease biomarkers the dizygotic correlations are often estimated to be less than half of monozygotic correlations indicating a potential influence of nonadditive genetic factors. Using a large and homogenous sample, we estimated the additive and dominance genetic influences on levels of high density lipoprotein, low density lipoprotein, apolipoprotein A-I, apolipoprotein B, total cholesterol, triglycerides, glucose, hemoglobin Alc and c-reactive protein, all of which are biomarkers associated with cardiovascular disease. The blood biomarkers were measured on 12,000 Swedish twins born between 1911 and 1958. The large sample allowed us to obtain heritability estimates with considerable precision and provided adequate statistical power for estimation of dominance genetic components. Our study showed complete absence of the shared environment component for the investigated traits. Dominant genetic component was shown to be significant for low density lipoprotein (0.18), glucose (0.31), Hemoglobin Alc (0.55), and c-reactive protein (0.27). To our knowledge, this is the first statistically significant evidence for dominance genetic variance found for low density lipoprotein, glucose, hemoglobin Alc, and c-reactive protein in a population based twin sample. The study highlights the importance of acknowledging nonadditive genes underlying the risk of developing cardiovascular diseases.

The Swedish Twin Registry (STR) today contains more than 194,000 twins and more than 75,000 pairs have zygosity determined by an intra-pair similarity algorithm, DNA, or by being of opposite sex. Of these, approximately 20,000, 25,000, and 30,000 pairs are monozygotic, same-sex dizygotic, and opposite-sex dizygotic pairs, respectively. Since its establishment in the late 1950s, the STR has been an important epidemiological resource for the study of genetic and environmental influences on a multitude of traits, behaviors, and diseases. Following large investments in the collection of biological specimens in the past 10 years we have now established a Swedish twin biobank with DNA from 45,000 twins and blood serum from 15,000 twins, which effectively has also transformed the registry into a powerful resource for molecular studies. We here describe the main projects within which the new collections of both biological samples as well as phenotypic measures have been collected. Coverage by year of birth, zygosity determination, ethnic heterogeneity, and influences of in vitro fertilization are also described.

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,rs2483058in an intron ofSRGAP2, where twins carrying the C allele are more sensitive to environmental factors (P= 3.98 × 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-II (P= 4.03 × 10−8).