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A longitudinal study of the relative contributions of genes, environement and interactions to blood lipid variation

English title A longitudinal study of the relative contributions of genes, environement and interactions to blood lipid variation
Applicant Gaspoz Jean-Michel
Number 108422
Funding scheme Project funding (special)
Research institution Division d'épidémiologie clinique Hôpital Cantonal Universitaire
Institution of higher education University of Geneva - GE
Main discipline Cardiovascular Diseases
Start/End 01.07.2005 - 30.06.2009
Approved amount 296'000.00
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Lay Summary (English)

Lay summary
There is evidence that both genetic and environmental factors, such as diet, physical activity, or drug treatments, control the concentrations of lipids in human blood. It is unknown, however, whether gene effects are independent of the non-genetic effects, or whether gene effects are modified by non-genetic factors in such a way that specific subgroups of the population harboring bad copies of the gene are more at risk than others when, for example, their diet is inadequate or they perform insufficient physical activity.We addressed this question in a population sample of 1543 adult Genevans. We sequenced all the exons of 11 genes involved in a metabolic pathway responsible for transporting cholesterol from peripheral tissues to the liver, where it is eliminated in the bile. We also assessed 10 non-genetic factors, including diet, physical activity, obesity, cigarette smoking, and alcohol intake. We used statistical procedures to select a subset of single nucleotide polymorphisms and non-genetic factors. Our final model indicated that cholesterol levels are independently determined by both non-genetic (body mass index (BMI) and alcohol intake p<.0001) and genetic (APOE2 p<.0001) factors, but with little evidence of gene-environment interactions. BMI was the single most important determinant for having an atherogenic extreme phenotype, explaining 27% of the lipid variance. The main limitation of this early work is that since cholesterol levels and non-genetic factors were assessed cross-sectionally at the same point in time, we cannot determine with certainty which factors influenced which. For example, does high cholesterol precede obesity or is it a consequence of obesity?We therefore are currently conducting a second study, in which we collect data from about 5000 subjects on non-genetic factors at two points in time, three to five years apart. With this new approach we will be able to assess the effects of non-genetic factor (say, obesity) over subsequent cholesterol changes over time. To our knowledge, this longitudinal study of the association of genetic and environmental factors on blood lipid levels is unique. While there many results about the association of genetic traits with cholesterolemia in populations exist, we know very little about how genes affect changes in cholesterolemia over time within individuals. This new research project may therefore generate results of great scientific interest.
Direct link to Lay Summary Last update: 21.02.2013

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