TWINGENE and GenomeEUtwin
A study on the importance of quantitative trait loci and environmental factors for cardiovascular disease - it is well known that genetic factors are of considerable importance for some familial lipid syndromes and that Type A Behavior pattern and increased lipid levels infer increased risk for cardiovascular disease.
It is known that genetic factors are of importance levels of blood lipid biomarkers. The interplay of genetic and environmental effects for these risk factors in a normal population is less well understood and virtually unknown for the elderly.
In the TwinGene project twins born before 1958 are contacted to participate. Health and medication data are collected from self-reported questionnaires, and blood sampling material is mailed to the subject who then contacts a local health care center for blood sampling and a health check-up. In the simple health check-up, height, weight, circumference of waist and hip, and blood pressure are measured. Blood is sampled for DNA extraction, serum collection and clinical chemistry tests of C-reactive protein, total cholesterol, triglycerides, HDL and LDL cholesterol, apolipoprotein A1 and B, glucose and HbA1C. The TwinGene cohort contains more than 10000 of the expected final number of 16000 individuals.
Molecular genetic techniques are being used to identify Quantitative Trait Loci (QTLs) for cardiovascular disease and biomarkers in the TwinGene participants. Genome-wide linkage and association studies are ongoing. DZ twins have been genome-scanned with 1000 STS markers and a subset of 300 MZ twins have been genome-scanned with Illumina 317K SNP platform. Association of positional candidate SNPs arising from these genome scans are planned.
The TwinGene project is associated with the large European collaboration denoted GenomeEUtwin which since 2002 has aimed at gathering genetic data on twins in Europe and setting up the infrastructure needed to enable pooling of data and joint analyses. It has been the funding source for obtaining the genome scan data.
Financing: NIH, EU, VR, SSF
Ulf de Faire, IMM, KI
Pennsylvania State Univ
Patrik Magnusson MEB, KI
Heritabilities of apolipoprotein and lipid levels in three countries.
Beekman M, Heijmans B, Martin N, Pedersen N, Whitfield J, DeFaire U, et al
Twin Res 2002 Apr;5(2):87-97
Two-locus linkage analysis applied to putative quantitative trait loci for lipoprotein(a) levels.
Beekman M, Heijmans B, Martin N, Whitfield J, Pedersen N, DeFaire U, et al
Twin Res 2003 Aug;6(4):322-4
Meta-analysis of four new genome scans for lipid parameters and analysis of positional candidates in positive linkage regions.
Heijmans B, Beekman M, Putter H, Lakenberg N, van der Wijk H, Whitfield J, et al
Eur. J. Hum. Genet. 2005 Oct;13(10):1143-53
Association between height and coronary heart disease mortality: a prospective study of 35,000 twin pairs.
Silventoinen K, Zdravkovic S, Skytthe A, McCarron P, Herskind A, Koskenvuo M, et al
Am. J. Epidemiol. 2006 Apr;163(7):615-21